Vaccines for Travel

Number: 0473

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses vaccines for travel.

1. Medical Necessity

   The following table lists vaccines that may be required for travel, and their medically necessary indications, standard administration schedule, and contraindications:

   Table: List of VaccinesFootnote1*

   Vaccine	Standard Schedule	Indications	Precautions and/or Contraindications
   Chikungunya Live, attenuated injectable vaccine (Ixchiq); or Recombinant injectable vaccine (Vimkunya)	Single intramuscular dose of chikungunya vaccine, live attenuated (Ixchiq, Valneva USA)	Note: A safety communication was issued by the FDA and CDC recommending a pause in administration of Ixchiq for persons 60 years and older due to post-marketing reports of serious adverse events, including death (FDA, 2025). For persons 18 years of age and older who are traveling to a country or territory where there is a chikungunya outbreak. In addition, the live attenuated chikungunya vaccine may be considered for persons aged 18 years or older traveling to a country or territory without an outbreak but with elevated risk for U.S. travelers if planning travel for an extended period of time (e.g., 6 months or more). Source: CDC, 2025	Contraindicated in immunocompromised individuals. May cause severe or prolonged chikungunya-like adverse reactions.  Vertical transmission of wild-type CHIKV from pregnant individuals with viremia at delivery is common and can cause potentially fatal CHIKV disease in neonates.  Safety and effectiveness in persons younger than 18 years have not been established. Source: Valneva USA, 2023
   	Single intramuscular dose of chikungunya vaccine, recombinant (virus-like particle chikungunya vaccine) (Vimkunya, Bavarian Nordic A/S)	For persons 12 years of age and older who are traveling to a country or territory without an outbreak but with elevated risk for U.S. travelers if planning travel for an extended period of time (e.g., 6 months or more) (CDC, 2025). For laboratory workersFootnote1* with potential for exposure to chikungunya virus. Source: CDC, 2025	Appropriate medical treatment must be immediately available to manage potential anaphylactic reactions following administration. Immunocompromised individuals, including individuals receiving  immunosuppressive therapy, may have a diminished immune response. Safety and effectiveness in persons younger than 12 years have not been established. Source: Bavarian Nordic A/S, 2025
   Cholera Live, attenuated oral vaccine (Vaxchora)	Lyophilized Vibrio cholerae CVD 103-HgR (Vaxchora, Bavarian Nordic A/S), after preparation, a single-dose, live attenuated oral cholera vaccine is administered a minimum of 10 days before potential exposure.	For persons 2 through 64 years of age traveling to endemic areas. Note: Vaccination is not routinely recommended because cholera is rare in travelers and most travelers do not visit areas of active transmission.	The effectiveness has not been established in persons living in cholera-affected areas; or in persons who have pre-existing immunity due to previous exposure to V. cholerae or receipt of a cholera vaccine. Has not been shown to protect against disease caused by V. cholerae serogroup O139 or other non-O1 serogroups. Safety in pregnancy unknown. Safety and effectiveness have not been established in persons 65 years of age or older, or in immunocompromised individuals. May be shed in the stool of recipients for at least 7 days. There is a potential for transmission of the vaccine strain to non-vaccinated close contacts (e.g., household contacts). Source: Bavarian Nordic A/S, 2025
   Dengue	see CPB 1010 - Dengue Vaccine
   Hepatitis A	see CPB 0048 - Hepatitis A Vaccine
   Hepatitis B	see CPB 0410 - Hepatitis B Vaccine
   Inactivated polio	see CPB 0402 - Polio Vaccine
   Japanese encephalitis (Ixiaro, Valneva USA, Inc.)	Primary: 2 doses (0.5 mL) intramuscularly administered 28 days apart. Booster: A booster dose (third dose) may be given at least 11 months after completion of the primary immunization series if ongoing exposure or re-exposure is expected.	Age 2 months and older; traveling to areas of risk with rural exposure or prolonged residence.	Contains protamine sulfate, a compound known to cause hypersensitivity reactions. Immunocompromised individuals may have a diminished immune response.Footnote2**
   Measles	Infants 6 months through 11 months of age should receive 1 dose of MMR vaccine.  Infants who get 1 dose of MMR vaccine before their 1st birthday should get 2 more doses (1 dose at 12 through 15 months of age and another dose at least 28 days later). Children 12 months of age and older should receive 2 doses of MMR vaccine separated by at least 28 days. Teenagers and adults who do not have evidence of immunity against measles should get 2 doses of MMR vaccine separated by at least 28 days.  Acceptable presumptive evidence of immunity against measles includes at least one of the following: written documentation of adequate vaccination, laboratory evidence of immunity, laboratory confirmation of measles, or birth in the United States before 1957.	Risk of exposure to measles.	Contraindications: Severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a vaccine component Known severe immunodeficiency (e.g., from hematologic and solid tumors, receipt of chemotherapy, congenital immunodeficiency, or long-term immunosuppressive therapy or patients with human immunodeficiency virus [HIV] infection who are severely immunocompromised).  Vaccine should be deferred for the appropriate interval if replacement immune globulin products are being administered.  HIV-infected children may receive varicella and measles vaccine if CD4+ T-lymphocyte count is greater than 15 %. Precautions: Moderate or severe acute illness with or without fever; recent (within 11 months) receipt of antibody-containing blood product (specific interval depends on product).  Vaccine should be deferred for the appropriate interval if replacement immune globulin products are being administered. History of thrombocytopenia or thrombocytopenic purpura. Need for tuberculin skin testing. Measles vaccination might suppress tuberculin reactivity temporarily. Measles-containing vaccine can be administered on the same day as tuberculin skin testing. If testing cannot be performed until after the day of MMR vaccination, the test should be postponed for at least 4 weeks after the vaccination. If an urgent need exists to skin test, do so with the understanding that reactivity might be reduced by the vaccine.
   Meningococcal vaccines	see CPB 0356 - Meningococcal Vaccines
   Oral polio	see CPB 0402 - Polio Vaccine
   Rabies (human diploid-cell vaccine)  Imovax Rabies (Sanofi Pasteur Inc.), RabAvert (Bavarian Nordic A/S)	Pre-exposure: 2-dose intramuscular series (days 0 and 7) Booster: Based on a risk-stratified approach.	For persons at high-risk of rabies exposure including international travelers who are likely to come in contact with animals in areas where dog rabies is enzootic.	Allergy to previous doses; may be given in pregnancy if indicated; rare neurologic or neuroparalytic events temporally associated with vaccination; immunocompromised individuals may have a diminished immune response.
   Tick-borne encephalitis virus vaccine (Ticovac)	Primary: 3 intramuscular doses 1 through 15 years of age: each dose 0.25 mL First dose: Day 0; Second dose: 1 to 3 months after 1st dose; Third dose: 5 to 12 months after 2nd dose. 16 years of age and older: each dose 0.5 mL First dose: Day 0; Second dose: 14 days to 3 months after 1st dose; Third dose: 5 to 12 months after 2nd dose. Booster:  A booster dose (fourth dose) may be given at least 3 years after completion of the primary immunization series if ongoing exposure or re-exposure to tickborne encephalitis virus (TBEV) is expected.	Indicated for active immunization to prevent tick-borne encephalitis (TBE). Ticovac is approved for use in individuals 1 year of age and older.	Contraindicated in those with severe allergic reaction (e.g., anaphylaxis) to any component of Ticovac. There are no adequate and well-controlled studies of Ticovac in pregnant women. Some individuals with altered immunocompetence may have reduced immune responses to Ticovac. Ticovac contains albumin. There is a theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD). Adverse reactions: 1 through 15 years of age: Local tenderness, local pain, headache, fever and restlessness. 16 through 65 years of age: Local tenderness, local pain, fatigue, headache and muscle pain.
   Typhoid Live‑attenuated oral Ty21a typhoid vaccine Vivotif (Bavarian Nordic A/S)	Primary 4 oral enteric‑coated capsules taken every other day timed around meals.  Revaccination with the full four‑dose series is recommended every 5 years for persons who remain at ongoing risk for exposure to Salmonella serotype Typhi.	For indivisuals 6 years of age or older at risk of exposure to typhoid fever.	Immunocompromised hostFootnote2**; enteric illness; concurrent antimicrobial treatment; Only given to pregnant women if clearly needed
   Typhoid, Vi capsular polysaccharide vaccine (ViCPS) Typhim Vi (Sanofi Pasteur, Inc)	Primary: Single-dose (0.5 mL) administered intramuscularly 2 or more weeks before travel.  Booster: A single-dose is recommended every 2 years for those who remain at risk.	For individuals 2 years of age or older who are at risk of exposure to typhoid fever.	Only given to pregnant women if clearly needed.
   Yellow fever  Live virus vaccine YF-VAX (Sanofi Pasteur, Inc)	Primary: A single primary dose (0.5 mL) subcutaneous injection provides long-lasting protection and is adequate for most travelers. Booster: Booster dose is not needed. However, travelers going to areas with ongoing outbreaks may consider getting a booster dose if it has been 10 years or more since they were last vaccinated. Certain countries may have a vaccination requirement.	Aged 9 months or older who are traveling to or living in areas at risk for yellow fever virus in Africa and South America; requirements and recommendations per individual countries.	Precautions in infants between 6 and 8 months old, over 60 years of age, pregnant or breastfeeding; contraindications include: hypersensitivity to eggs; in persons less than 6 months of age per CDC (less than 9 months of age per FDA-approved labeling), immunosuppressed individuals, organ transplant recipients
   Zaire ebolavirus vaccine Live (Ervebo)	Primary: Single 1 mL dose administered intramuscularly. Booster: Not recommended.	Indicated for the prevention of disease caused by Zaire ebolavirus in individuals 18 years of age and older. Limitations:  The duration of protection conferred is unknown. Vaccine does not protect against other species of Ebolavirus or Marburgvirus. Effectiveness of the vaccine when administered concurrently with antiviral medication, immune globulin (IG), and/or blood or plasma transfusions is unknown.	Anaphylaxis has been observed following administration of vaccine.  Vaccinated individuals should continue to adhere to infection control practices to prevent Zaire ebolavirus infection and transmission.  Vaccine virus RNA has been detected in blood, saliva, urine, and fluid from skin vesicles of vaccinated adults; transmission of vaccine virus is a theoretical possibility.

   Footnote1* Most Aetna benefit plans exclude coverage of vaccines for work. Please check benefit plan descriptions.

   Footnote2** Persons who are immunocompromised because of immune deficiency diseases, leukemia, lymphoma, generalized cancer, or the acquired immunodeficiency syndrome, or who are receiving immunosuppressive therapy with corticosteroids, alkylating agents, anti-metabolites, or radiation.

   Note: The Advisory Committee on Immunization Practices (1996) states that plague vaccination is not indicated for most travelers to countries in which cases of plague have been reported.

2. Experimental, Investigational, or Unproven

   The following vaccines for travel are considered experimental, investigational, or unproven (not an all-inclusive list):

   1. Malaria vaccine for travel because an effective malaria vaccine has yet to be developed.
   2. Cholera vaccine for all other indications not listed in Section 1 including prevention of entero-toxigenic Escherichia coli diarrhea because the clinical value has not been established.

3. Policy Limitations and Exclusions 

   Note: Most Aetna HMO plans exclude coverage of vaccines for travel. Most Aetna traditional plans cover medically necessary travel vaccines for members of plans with preventive services benefits.  Please check benefit plan descriptions.

   Note: Many of these vaccines may also be considered medically necessary for reasons other than travel, and may be covered when medically necessary in members with preventive benefits, regardless of whether the plan excludes coverage of travel vaccines.

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Table:

CPT Codes/ HCPCS Codes / ICD-10 Codes

Code	Code Description
CPT codes covered if selection criteria are met:
90589	Chikungunya virus vaccine, live attenuated, for intramuscular use
90593	Chikungunya virus vaccine, recombinant, for intramuscular use
90625	Cholera vaccine, live, adult dosage, 1 dose schedule, for oral use [covered for age 2 – 64 only]
90626	Tick-borne encephalitis virus vaccine, inactivated; 0.25 mL dosage, for intramuscular
90627	0.5 mL dosage, for intramuscular use
90675	Rabies vaccine, for intramuscular use
90676	Rabies vaccine, for intradermal use
90690	Typhoid vaccine, live, oral
90691	Typhoid vaccine, Vi capsular polysaccharide (ViCPs), for intramuscular use
90707	Measles, mumps and rubella virus vaccine (MMR), live, for subcutaneous use
90710	Measles, mumps, rubella, and varicella vaccine (MMRV), live, for subcutaneous use
90717	Yellow fever vaccine, live, for subcutaneous use
90738	Japanese encephalitis virus vaccine, inactivated, for intramuscular use
90758	Zaire ebolavirus vaccine, live, for intramuscular use
Other CPT codes related to the CPB:
90460	Immunization administration through 18 years of age via any route of administration, with counseling by physician or other qualified health care professional; first vaccine/toxoid component
+90461	each additional vaccine/toxoid component
90471	Immunization administration (includes percutaneous, intradermal, subcutaneous, or intramuscular injections); one vaccine (single or combination vaccine/toxoid)
+ 90472	each additional vaccine (single or combination vaccine/toxoid) (list separately in addition to code for primary procedure)
90473	Immunization administration by intranasal or oral route; one vaccine (single or combination vaccine/toxoid)
+ 90474	each additional vaccine (single or combination vaccine/toxoid) (list separately in addition to code for primary procedure)
90482	Immunization counseling by physician or other qualified health care professional when immunization(s) is not administered by provider on the same date of service; 3 minutes up to 10 minutes
90483	greater than 10 minutes up to 20 minutes
90484	greater than 20 minutes
90644	Meningococcal conjugate vaccine, serogroups C & Y and Haemophilus influenzae type b vaccine (Hib-MenCY), 4 dose schedule, when administered to children 6 weeks-18 months of age, for intramuscular use
HCPCS codes covered if selection criteria are met:
G0010	Administration of hepatitis B vaccine
Other HCPCS codes related to the CPB:
G0310	Immunization counseling by a physician or other qualified health care professional when the vaccine(s) is not administered on the same date of service, 5 to 15 mins time (this code is used for Medicaid billing purposes)
G0311	Immunization counseling by a physician or other qualified health care professional when the vaccine(s) is not administered on the same date of service, 16-30 mins time (this code is used for Medicaid billing purposes)
G0312	Immunization counseling by a physician or other qualified health care professional when the vaccine(s) is not administered on the same date of service for ages under 21, 5 to 15 mins time (this code is used for Medicaid billing purposes)
G0313	Immunization counseling by a physician or other qualified health care professional when the vaccine(s) is not administered on the same date of service for ages under 21, 16-30 mins time (this code is used for Medicaid billing purposes)
ICD-10 codes covered if selection criteria are met:
A83.0	Japanese encephalitis
A95.9	Yellow fever, unspecified
Z23	Encounter for immunization

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Background

The Centers for Disease Control and Prevention (CDC)'s recommended vaccinations for travelers can be found at the following website: Destinations and Travelers Health.

Chikungunya Vaccine

Chikungunya is primarily a mosquito-borne alphavirus caused by the chikungunya virus (CHIKV) that is often associated with fever and debilitating joint pain. Rarely, the virus can be transmitted via blood products, laboratory and maternal-fetal transmission. Outbreaks typically occur in tropical and subtropical regions of Africa, Asia, Oceania, and parts of the Americas and Europe where chikungunya virus-carrying mosquitos are endemic (Bettis et al, 2022; Wilson and Lenschow, 2022). Between 2014 and 2016, 3,941 cases were reported in the United States among travelers; 92% were associated with travel in the Americas (most commonly the Dominican Republic, Puerto Rico, and Haiti). The remaining 8% had traveled to Asia, Africa, or the Western Pacific (Lindsey et al, 2018; Wilson and Lenschow, 2022).

Management of the chikungunya virus is supportive (i.e., rest, fluids, anti-inflammatory and analgesic agents). Systemic glucocorticoids or treatment with a disease-modifying antirheumatic drug (DMARD) has been used in refractory or chronic arthritis cases. The cornerstone of prevention has been minimizing mosquito exposure (Lenschow and Wilson, 2023). In November 2023, the FDA approved the first chikungunya vaccine (Ixchiq, Valneva USA Inc.) for the prevention of disease caused by chikungunya virus (CHIKV) in individuals 18 years of age and older who are at increased risk of exposure to CHIKV. "This indication is approved under accelerated approval based on anti-CHIKV neutralizing antibody titers. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory studies" (Valneva, 2023).

FDA approval was based on two clinical trials conducted in North America that evaluated the safety of Ixchiq in adults 18 years or older. In clinical studies, the most common solicited injection site reaction (greater than 10%) was tenderness (10.6%). The most common solicited systemic adverse reactions (greater than 10%) were headache (31.6%), fatigue (28.5%), myalgia (23.9%), arthralgia (17.2%), fever (13.5%) and nausea (11.2%). The effectiveness was based on immune response data from a clinical study conducted in the US in adults. "In this study, the immune response of 266 participants who received the vaccine was compared to the immune response of 96 participants who received placebo. The level of antibody evaluated in study participants was based on a level shown to be protective in non-human primates that had received blood from people who had been vaccinated. Almost all vaccine study participants achieved this antibody level" (FDA, 2023).

Ixchiq is administered as a single intramuscular injection. Ixchiq contains a live, weakened version of the chikungunya virus and may cause symptoms in the vaccine recipient similar to those experienced by people who have chikungunya disease. It is contraindicated in immunocompromised individuals or those with a history of a severe allergic reaction to any component of Ixchiq. Vertical transmission of wild-type CHIKV from pregnant individuals with viremia at delivery is common and can cause potentially fatal CHIKV disease in neonates. Vaccine viremia occurs in the first week following administration of Ixchiq, with resolution of viremia by 14 days after vaccination. It is not known if the vaccine virus can be vertically transmitted and cause fetal or neonatal adverse reactions. A decision to administer during pregnancy should take into consideration the individual’s risk of wild-type CHIKV infection, gestational age, and risks to the fetus or neonate from vertical transmission of wild-type CHIKV. Labeled warnings and precautions also include severe or prolonged chikungunya-like adverse reactions, vertical transmission of wild-type CHIKV from pregnant individuals with viremia at delivery is common and can cause potentially fatal CHIKV disease in neonates, and risk of syncope associated with administration of injectable vaccines (Valneva, 2023).

In clinical studies, the most common solicited injection site reaction (greater than 10%) was tenderness (10.6%). The most common solicited systemic adverse reactions (greater than 10%) were headache (31.6%), fatigue (28.5%), myalgia (23.9%), arthralgia (17.2%), fever (13.5%) and nausea (11.2%).

The Centers for Disease Control's (CDC) Advisory Committee on Immunization Practices (ACIP) met in October 2023 to discuss recommendations for the chikungunya vaccine. Draft recommendations include chikungunya vaccine recommendation for persons 18 years of age and older traveling to a country or territory where there is a chikungunya outbreak. In addition, the vaccine may be considered for persons traveling to a country or territory without an outbreak but with evidence of chikungunya virus transmission among humans within the last 5 years:

• Older persons (e.g., >65 years), particularly those with underlying medical conditions, who are likely to have at least moderate exposure (moderate exposure could include travelers who might have at least 2 weeks (cumulative) of exposure to mosquitoes in indoor and/or outdoor settings) to mosquitoes
• Persons staying for a cumulative period of 6 months or more during a 2-year period.

In February 2025, the FDA approved an injectable recombinant chikungunya vaccine, Vimkunya (Bavarian Nordic A/S) as the first virus-like particle (VLP) single-dose chikungunya vaccine in the U.S. for persons 12 years of age and older.  FDA approval was based on results from two phase 3 clinical trials which enrolled more than 3,500 healthy individuals 12 years of age and older. Primary endpoints were met in the phase 3 trials, with results showing that 21 days after vaccination, Vimkunya induced neutralizing antibodies in up to 97.8% of individuals vaccinated and demonstrated a rapid immune response starting to develop within one week. The vaccine was well-tolerated and adverse events were mainly mild or moderate in nature (Bavarian Nordic A/S, 2025a).

The ACIP first approved recommendations for use in U.S. travelers and laboratory workers in February 2024; however, later revised traveler recommendations in May 2025. The ACIP approved the following recommendations for the chikungunya vaccine:

• ACIP recommends the virus-like particle chikungunya vaccine (Vimkunya, Bavarian Nordic A/S ) for persons aged 12 years or older traveling to a country or territory where there is a chikungunya outbreak. In addition, the virus-like particle chikungunya vaccine may be considered for persons aged 12 years or older traveling or taking up residence in a country or territory without an outbreak but with elevated risk for U.S. travelers if planning travel for an extended period of time (e.g., 6 months or more);
• ACIP recommends the virus-like particle chikungunya vaccine for laboratory workers with potential for exposure to chikungunya virus;
• ACIP recommends the live attenuated chikungunya vaccine (Ixchiq, Valneva USA Inc.) for persons aged 18 years or older traveling to a country or territory where there is a chikungunya outbreak. In addition, the live attenuated chikungunya vaccine may be considered for persons aged 18 years or older traveling or taking up residence in a country or territory without an outbreak but with elevated risk for U.S. travelers if planning travel for an extended period of time (e.g., 6 months or more).

On May 9, 2025, the FDA and CDC released a safety communication recommending a pause in the use of Ixchiq (live attenuated vaccine) in individuals 60 years of age and older while post-marking safety reports are investigated. As of May 7, 2025, 17 serious adverse events, including two that resulted in death, have been reported in individuals 62 through 89 years of age who received Ixchiq during post-marketing use globally. Six of these reports have been from the U.S.. Most U.S. and foreign serious adverse events that have been reported to the Vaccine Adverse Event Reporting System (VAERS), co-managed by FDA and CDC, have been in individuals with underlying chronic medical conditions. Adverse events reported to VAERS may not be causally related to vaccination. Approximately 80,000 doses of Ixchiq have been distributed globally (FDA, 2025).

Cholera

Cholera is an acute diarrheal disease caused by toxigenic Vibrio cholerae (primarily serogroup O1). Infection is acquired through ingestion of contaminated water or food and can result in profuse watery diarrhea, vomiting, and rapid dehydration. Without prompt rehydration, cholera can be fatal. Cholera is rare in the United States and most U.S. cases occur among travelers to countries with endemic or epidemic transmission.

In a Cochrane review, Ahmed et al. (2013) evaluated the safety, effectiveness, and immunogenicity of vaccines for preventing entero-toxigenic Escherichia coli (ETEC) diarrhea. These investigators searched the Cochrane Infectious Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, and ClinicalTrials up to December 2012. Randomized controlled trials (RCTs) and quasi-RCTs comparing the use of vaccines to prevent ETEC with no intervention, a control vaccine (either an inert vaccine or a vaccine normally given to prevent an unrelated infection), an alternative ETEC vaccine, or a different dose or schedule of the same ETEC vaccine in healthy adults and children living in endemic regions, intending to travel to endemic regions, or volunteering to receive an artificial challenge of ETEC bacteria were included for analysis. Two authors independently assessed each trial for eligibility and risk of bias. Two independent reviewers extracted data from the included studies and analyzed the data using Review Manager (RevMan) software. They reported outcomes as risk ratios (RR) with 95% confidence intervals (CI) and assessed the quality of the evidence using the GRADE approach. A total of 24 RCTs, including 53,247 participants, met the inclusion criteria—four studies assessed the protective efficacy of oral cholera vaccines when used to prevent diarrhea due to ETEC, and seven studies assessed the protective efficacy of ETEC-specific vaccines. Of these 11 studies, seven presented efficacy data from field trials, and four presented efficacy data from artificial challenge studies. An additional 13 trials contributed safety and immunological data only. The oral cholera killed whole cell vaccine (Dukoral®) was evaluated for protection against "travelers' diarrhea" in a single RCT involving people arriving in Mexico from the USA. These researchers did not identify any statistically significant effects on ETEC diarrhea or all-cause diarrhea (1 trial, 502 participants; low-quality evidence). Two earlier trials, one conducted in an endemic population in Bangladesh and one involving travelers from Finland to Morocco, evaluated a precursor of this vaccine containing purified cholera toxin B subunit rather than the recombinant subunit in Dukoral®. Short-term protective efficacy against ETEC diarrhea was demonstrated, lasting for around 3 months (RR 0.43, 95% CI: 0.26 to 0.71; 2 trials, 50,227 participants). This vaccine is no longer available. An ETEC-specific, killed whole cell vaccine, which also contains the recombinant cholera toxin B-subunit, was evaluated in people traveling from the USA to Mexico or Guatemala, and from Austria to Latin America, Africa, or Asia. These investigators did not identify any statistically significant differences in ETEC-specific diarrhea or all-cause diarrhea (2 trials, 799 participants), and the vaccine was associated with increased vomiting (RR 2.0, 95% CI: 1.16 to 3.45; 9 trials, 1,528 participants). The other ETEC-specific vaccines in development have not yet demonstrated clinically important benefits. The authors concluded that there is currently insufficient evidence from RCTs to support the use of the oral cholera vaccine Dukoral® for protecting travelers against ETEC diarrhea. Moreover, they stated that further research is needed to develop safe and effective vaccines to provide both short- and long-term protection against ETEC diarrhea.

The Centers for Disease Control and Prevention (CDC) does not recommend routine cholera vaccination for the general U.S. population or for most travelers because cholera infection among travelers is rare and most travelers do not visit areas of active transmission. However, the CDC does recommend CVD 103-HgR (Vaxchora) for travelers ages 2 to 64 years old going to areas of active toxigenic Vibrio cholerae O1 transmission (i.e., widespread, localized, or presumed) (Collins et al., 2022).

In 2016, the U.S. Food and Drug Administration (FDA) approved Vaxchora (Bavarian Nordic A/S) for active immunization against disease caused by Vibrio cholerae serogroup O1 in persons 2 through 64 years of age traveling to cholera-affected areas. 

Vaxchora is a live, attenuated vaccine for oral administration only. It is administered a minimum of 10 days before potential exposure. 

The effectiveness of Vaxchora has not been established in persons living in cholera-affected areas, or in persons who have pre-existing immunity due to previous exposure to V. cholerae or receipt of a cholera vaccine. Vaxchora has not been shown to protect against disease caused by V. cholerae serogroup O139 or other non-O1 serogroups. Moreover, the safety and effectiveness have not been established in immunocompromised persons. Vaxchora may be shed in the stool of recipients for at least 7 days. There is a potential for transmission of the vaccine strain to non-vaccinated close contacts (e.g., household contacts). The label advised to use caution when considering whether to administer Vaxchora to individuals with immunocompromised close contacts.

The most common adverse reactions for adults (incidence greater than 3%) were tiredness (31%), headache (29%), abdominal pain (19%), nausea/vomiting (18%), lack of appetite (17%) and diarrhea (4%); and for children and adolescents (incidence 10% or more) were:

• Age 12 to 17 years: headache (45%), tiredness (41%), abdominal pain (38%), lack of appetite (29%) and nausea (22%)
• Age 6 to 11 years: tiredness (35%), abdominal pain (27%), headache (26%), lack of appetite (15%) and nausea (14%)
• Age 2 to 5 years: tiredness (31%), loss of appetite (19%), and abdominal pain (17%).

Lyme Disease

According to the Centers for Disease Control and Prevention website (CDC, 2026), a vaccine for Lyme disease is not currently available. The only vaccine previously marketed in the United States, LYMERix®, was discontinued by the manufacturer in 2002, citing insufficient consumer demand. Protection provided by this vaccine decreases over time. Therefore, individuals who received this vaccine before 2002, are no longer protected against Lyme disease.

Malaria

In a Cochrane review on vaccines for preventing malaria, Graves and Gelband (2006a) concluded that there is no evidence for protection by SPf66 vaccines against P. falciparum in Africa. There is a modest reduction in attacks of P. falciparum malaria following vaccination with SPf66 in South America. There is no justification for further trials of SPf66 in its current formulation. Further research with SPf66 vaccines in South America or with new formulations of SPf66 may be justified.

In another Cochrane review, Graves and Gelband (2006b) concluded that the MSP/RESA (Combination B) vaccine shows promise as a way to reduce the severity of malaria episodes, but the effect of the vaccine is MSP2 variant-specific. Pre-treatment for malaria during a vaccine trial makes the results difficult to interpret, particularly with the relatively small sample sizes of early trials. The results show that blood-stage vaccines may play a role and merit further development.

Vaughan et al. (2009) presented a comprehensive meta-analysis of more than 500 references, describing nearly 5,000 unique B cell and T cell epitopes derived from the Plasmodium genus, and detailing thousands of immunological assays. This was the first inventory of epitope data related to malaria-specific immunology, plasmodial pathogenesis, and vaccine performance. The survey included host and pathogen species distribution of epitopes, the number of antibody versus CD4(+) and CD8(+) T cell epitopes, the genomic distribution of recognized epitopes, variance among epitopes from different parasite strains, and the characterization of protective epitopes and of epitopes associated with parasite evasion of the host immune response. The results identified knowledge gaps and areas for further investigation. This information has relevance to issues such as the identification of epitopes and antigens associated with protective immunity, the design and development of candidate malaria vaccines, and characterization of immune response to strain polymorphisms.

Plague

The Advisory Committee on Immunization Practices (ACIP) of the CDC provided the following recommendations regarding the prevention of plague (1996):

• Routine plague vaccination is not necessary for individuals living in areas in which plague is enzootic.
• Plague vaccination is not indicated for hospital staff or other medical personnel in such areas.
• Plague vaccination is not indicated for most travelers to countries in which cases of plague have been reported.

The CDC continues to not recommend routine vaccination against plague. According to CDC ACIP guidance, because human plague is rare, vaccination is not indicated for the general population, for people living in enzootic areas (including the western United States), for most travelers, or for clinical laboratory workers. Additionally, there is no plague vaccine licensed for general use in the United States (CDC, 2025).

Rabies

Rabies is an acute, progressive encephalitis caused by rabies virus, a Lyssavirus, that is transmitted to humans through the saliva of infected mammals, most commonly by bites, and is almost universally fatal once clinical symptoms appear; early manifestations include fever and paresthesia at the exposure site, followed by neurologic signs such as agitation, hydrophobia, aerophobia, and coma.

The ACIP (2022) published a clinical practice guideline to update recommendations for rabies preexposure prophylaxis in the United States, addressing vaccination schedules, exposure risk stratification, antibody titer monitoring, and long-term immunogenicity for persons at increased risk of rabies exposure. The guideline scope encompassed occupational, recreational, and travel-related risk and redefined five risk categories based on recognized versus unrecognized exposures and sustained versus time-limited risk, while applying to both immunocompetent and immunocompromised persons. The guideline evaluated immunogenicity and management of rabies preexposure prophylaxis, including primary vaccination schedules and approaches to maintaining long-term protection, and reported evidence from reviewed studies showing comparable primary immunogenicity between a 2-dose intramuscular schedule administered on days 0 and 7 and a 3-dose schedule administered on days 0, 7, and 21 or 28, with a reported risk ratio of 1.00 (95% CI, 0.99–1.01) across 12 studies enrolling a combined total of 1,401 subjects. The ACIP recommended a 2-dose intramuscular primary rabies vaccination series on days 0 and 7 for all persons for whom preexposure prophylaxis was indicated, established a minimum acceptable rabies antibody titer of ≥0.5 IU/mL, and specified long-term immunogenicity management by risk category, including rabies antibody titer checks every 6 months for risk category 1 and every 2 years for risk category 2 with booster vaccination if titers were <0.5 IU/mL, and for risk category 3 either a one-time antibody titer check during years 1–3 after the primary series with booster vaccination if titers were <0.5 IU/mL or a one-time booster dose administered no sooner than day 21 and no later than year 3 after the primary series; persons in risk category 4 required no additional titers or booster doses, and persons in risk category 5 were not recommended to receive rabies preexposure prophylaxis. The guideline stated that long-term immunogenicity beyond 3 years after completion of the 2-dose primary series had not been directly evaluated and identified this as a limitation (Rao et al., 2022).

The Centers for Disease Control's Advisory Committee on Immunization Practices (ACIP) recommends rabies pre‑exposure prophylaxis (PrEP) vaccination for people who work directly with animals that could have rabies and for those who travel to parts of the world where rabies is common and access to medical care is limited, as most people in the United States have a low risk of being around an animal with rabies but a small subset are at higher risk. These individuals should receive rabies PrEP, a series of rabies vaccine doses given before exposure to the rabies virus. The ACIP rabies PrEP recommendations state that a 2‑dose PrEP schedule has replaced the 3‑dose PrEP schedule to protect people from rabies for up to 3 years. The minimum acceptable laboratory value (antibody titer) used to determine whether rabies vaccine booster doses are needed was revised and standardized, and many people for whom serial titers were recommended every 2 years now require only a one‑time titer (and booster if below a certain level) or a one‑time booster. Risk categories have been redefined into 5 risk groups, ranging from people who work with live or concentrated rabies virus in laboratories and require titer checks every 6 months, to the general U.S. population for whom no vaccination is recommended, with specific vaccination, titer, or booster recommendations based on the level and duration of risk (CDC, 2025).

Rabies Pre‑Exposure Prophylaxis (PrEP) Risk Categories

Risk Category 1 (Highest)

• Population: Laboratory workers handling live or concentrated rabies virus
• Vaccination: 2 doses (days 0, 7)
• Monitoring: Titer every 6 months

Risk Category 2

• Population: Frequent bat exposure (handling bats, bat contact, caves, animal necropsies)
• Vaccination: 2 doses (days 0, 7)
• Monitoring: Titer every 2 years

Risk Category 3

• Population: Ongoing risk (>3 years) from mammals other than bats (e.g., veterinarians, animal control, wildlife workers, spelunkers, certain travelers outside U.S. where rabies in dogs is commonly found)
• Vaccination: 2 doses (days 0, 7) plus either:
  
  
  • One‑time titer check 1–3 years after first 2-dose series; or
  • One‑dose booster between 3 weeks and 3 years after first vaccine in the 2-dose series

Risk Category 4

• Population: Same as Category 3, but risk ≤3 years after receiving PrEP
• Vaccination: 2 doses (days 0, 7)

Risk Category 5 (Lowest)

• Population: General U.S. population
• Vaccination: Not recommended

There are two FDA-approved  rabies PrEP vaccines available in the U.S., Imovax (Sanofi Pasteur) and RabAvert (Bavarian Nordic). Both vaccines are administered intramuscularly and are considered equally safe and effective. They are interchangeable, meaning if you start a series with one, you can complete it with the other if necessary.

Imovax Rabies is associated with specific warnings and precautions. Individuals with altered immunocompetence, including those receiving immunosuppressive therapy, may have a reduced immune response to vaccination. Serum sickness–type reactions have been reported following booster doses administered for pre‑exposure prophylaxis, typically occurring 2 to 21 days after vaccination and characterized by generalized urticaria, with possible arthralgia, arthritis, angioedema, nausea, vomiting, fever, and malaise; none of the reported reactions were life‑threatening and have been reported in up to 7% of individuals receiving booster vaccination. Rare neurologic illnesses temporally associated with Imovax Rabies, including illnesses resembling Guillain‑Barré syndrome, a transient neuroparalytic illness that resolved without sequelae, and focal subacute central nervous system disorders, have been reported. The vaccine contains albumin, a derivative of human blood, and carries an extremely remote risk for transmission of viral diseases and variant Creutzfeldt‑Jakob disease; no cases of transmission have been identified. There are no adequate and well‑controlled studies of Imovax Rabies in pregnant women, data in pregnant women are insufficient to inform vaccine‑associated risks in pregnancy, and animal reproduction studies have not been conducted. Vaccination with Imovax Rabies may not protect all individuals (Sanofi Pasteur, 2025).

RabAvert is contraindicated for pre‑exposure prophylaxis in individuals with a history of anaphylaxis to the vaccine or any of its components; however, because rabies is almost invariably fatal, there are no contraindications to post‑exposure prophylaxis, including during pregnancy. Warnings and precautions include the risk of severe hypersensitivity reactions, and patients at risk for such reactions should receive an alternative rabies vaccine if available. Anaphylaxis and rare neurologic and neuroparalytic events temporally associated with RabAvert have been reported, including meningitis, encephalitis, transient paralysis, Guillain‑Barré syndrome, myelitis, retrobulbar neuritis, and multiple sclerosis; decisions to discontinue immunization should carefully consider the patient’s risk of developing rabies. Syncope and unintentional intravascular injection–related systemic reactions have been reported. Development of active immunity may be impaired in immunocompromised individuals. RabAvert contains human albumin and carries an extremely remote risk of transmission of viral diseases or Creutzfeldt‑Jakob disease, with no cases identified. The vaccine contains residues of egg and chicken proteins, processed bovine gelatin, and trace amounts of neomycin, chlortetracycline, and amphotericin B, which may pose a risk of allergic reactions in susceptible individuals. Long‑term studies to evaluate carcinogenicity, mutagenesis, or impairment of fertility have not been conducted. Animal reproductive studies have not been conducted, and it is not known whether RabAvert can cause fetal harm or affect reproductive capacity; RabAvert should be used during pregnancy only if clearly needed. Vaccination with RabAvert may not protect 100% of susceptible individuals (Bavarian Nordic, 2025d).

Per the CDC's Yellow Book (2025), rabies PrEP dose recommendation for infants and children is the same as adults.

Japanese Encephalitis Vaccine for Pediatric Travelers

Japanese encephalitis (JE) is a mosquito-borne viral disease caused by a flavivirus and is a leading cause of viral encephalitis in Asia and parts of the western Pacific. Most infections are asymptomatic, but clinical disease can include fever, headache, altered mental status, seizures, and focal neurologic deficits, with a reported case-fatality rate of approximately 20–30% and long-term neurologic or psychiatric sequelae in 30–50% of survivors. Vaccination is the primary strategy for prevention, in conjunction with mosquito-avoidance measures. In the United States, the inactivated Vero cell–derived JE vaccine (IXIARO®) is licensed for use in persons aged ≥2 months and is recommended by the Centers for Disease Control and Prevention (CDC) for travelers and laboratory workers at risk of exposure. The standard primary series consists of 2 doses administered 28 days apart, with a booster recommended for ongoing risk. JE vaccines have been shown to be immunogenic and effective, and serious adverse events are uncommon according to post-licensure surveillance and clinical studies (CDC, 2024, Hills et al., 2019; Hills and Lindsey, 2026).

Taucher and colleagues (2020) stated that in an initial study among children from non-Japanese encephalitis (JE)-endemic countries, sero-protection rates (SPRs) remained high 6 months following completion of the primary series with IXIARO. In an open-label, follow-up study, a subset of 23 children who received a 2-dose primary series of IXIARO in the parent study, were examined for safety and neutralizing antibody persistence for 36 months. SPRs remained high but declined from 100% 1 month after primary immunization to 91.3% at month 7 and 89.5% at month 36. Geometric mean titers (GMTs) declined considerably from 384.1 by day 56-60.8 at month 36. No long-term safety concerns were identified. The authors concluded that the substantial decline in GMT observed in this study, together with previously published data on children vaccinated with IXIARO supported the recommendation for a booster dose in children who remain at risk of JE from 1 year after the primary series of IXIARO, consistent with the recommendation for adults.

Measles

Jost and colleagues (2015) evaluated the relevance of travel-related measles, a highly transmissible and vaccine-preventable disease. Between 2001 and 2013, surveillance and travel-related measles data were systematically reviewed according to the PRISMA guidelines with extraction of relevant articles from Medline, Embase, GoogleScholar and from public health authorities in the Region of the Americas, Europe and Australia. From a total of 960 records, 44 articles were included and they comprised 2,128 imported measles cases between 2001 and 2011. The proportion of imported cases in Europe was low at 1 to 2%, which reflected the situation in a measles-endemic region. In contrast, imported and import-related measles accounted for up to 100% of all cases in regions with interrupted endemic measles transmission; 11 air-travel related reports described 132 measles index cases leading to 47 secondary cases. Secondary transmission was significantly more likely to occur if the index case was younger or when there were multiple infectious cases on board. Further spread to health care settings was found. Measles cases associated with cruise ship travel or mass gatherings were sporadically observed. The authors concluded that within both, endemic and non-endemic home countries, pre-travel health advice should assess MMR immunity routinely to avoid measles spread by non-immune travelers. They stated that to identify measles spread as well as to increase and sustain high vaccination coverages, joint efforts of public health specialists, health care practitioners and travel medicine providers are needed.

The CDC (2015) states that anyone who is not protected against measles is at risk of getting infected when they travel internationally. It recommends the following: Centers for Disease Control and Prevention.

• Infants 6 months through 11 months of age should receive 1 dose of MMR vaccineFootnote3***
• Children 12 months of age and older should receive 2 doses of MMR vaccine separated by at least 28 days.
• Teenagers and adults who do not have evidence of immunityFootnote4† against measles should get 2 doses of MMR vaccine separated by at least 28 days.

Footnote3*** Infants who get 1 dose of MMR vaccine before their first birthday should get 2 more doses (1 dose at 12 through 15 months of age and another dose at least 28 days later).

Footnote4† Acceptable presumptive evidence of immunity against measles includes at least one of the following: written documentation of adequate vaccination, laboratory evidence of immunity, laboratory confirmation of measles, or birth in the United States before 1957.

Contraindications and Precautions: Vaccine Recommendations and Guidelines of the ACIP.

Contraindications

• Severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a vaccine component
• Known severe immunodeficiency (e.g., from hematologic and solid tumors, receipt of chemotherapy, congenital immunodeficiency, or long-term immunosuppressive therapyFootnote5†† or patients with human immunodeficiency virus [HIV] infection who are severely immunocompromised)Footnote6†††
• Pregnancy

Footnote5†† Vaccine should be deferred for the appropriate interval if replacement immune globulin products are being administered.

Footnote6††† HIV-infected children may receive varicella and measles vaccine if CD4+ T-lymphocyte count is greater than 15 %.

Precautions

• Moderate or severe acute illness with or without fever
• Recent (within 11 months) receipt of antibody-containing blood product (specific interval depends on product)Footnote7‡
• History of thrombocytopenia or thrombocytopenic purpura
• Need for tuberculin skin testingFootnote8‡‡

Footnote7‡ Vaccine should be deferred for the appropriate interval if replacement immune globulin products are being administered

Footnote8‡‡ Measles vaccination might suppress tuberculin reactivity temporarily. Measles-containing vaccine can be administered on the same day as tuberculin skin testing. If testing cannot be performed until after the day of MMR vaccination, the test should be postponed for at least 4 weeks after the vaccination. If an urgent need exists to skin test, do so with the understanding that reactivity might be reduced by the vaccine.

Tick-Borne Encephalitis Vaccine

Rampa et al. (2020) state that tick-borne encephalitis (TBE) is increasing in Europe and has become one of the most important causes of viral encephalitis, as well as the most frequent cause of viral meningitis, in Europe. The authors note that there is no antiviral treatment against TBE and that active vaccination is a practical preventive measure to reduce the number of cases. There are two inactivated virus vaccines licensed in Europe: FSME-Immun® (Pfizer), distributed as Ticovac® in some countries, and Encepur® (Bavarian Nordic). FSME-Immun is based on the TBE virus strain Neudoerfl (Nd), whereas Encepur is based on the TBE virus strain Karlsruhe-23 (K23). Both vaccines have a pediatric TBE vaccine variant. Thus, the authors conducted a systematic review (registered at PROSPERO (#CRD42020155737) and conducted in accordance with PRISMA guidelines) of the immunogenicity and safety of the tick-borne encephalitis vaccine (2009-2019). Of a total of 2,464 records, 49 original research publications included evaluation for immunogenicity and safety. The authors found that TBE vaccines showed adequate immunogenicity, good safety, and interchangeability in adults and children, with some differences in long-term protection (seropositivity in 90.6–100% after primary vaccination; 84.9%–99.4% at 5-year follow-up). The primary conventional vaccination schedule (days 0, 28, and 300) demonstrated the best immunogenic results (99–100% of seropositivity). Mixed brand primary vaccination presented adequate safety and immunogenicity with some exceptions. After booster follow-ups, accelerated conventional and rapid vaccination schedules were shown to be comparable in terms of immunogenicity and safety. First booster vaccinations five years after primary vaccination were protective in adults aged less than 50 years, leading to protective antibody levels from at least 5 years up to 10 years after booster vaccination. In older vaccinees, aged 50 years and older, lower protective antibody titers were found. Allergic individuals showed an adequate response, while immunosuppressed individuals exhibited a diminished response to TBE vaccination. The authors concluded that TBE vaccination with Encepur or FSME-Immun is highly immunogenic, well tolerated, and interchangeable in all studies except one. Schedules should, if possible, use the same vaccine brand (non-mixed). TBE vaccines are immunogenic in terms of antibody response but less so when vaccination is started after the age of 50 years. Age at priming is a key factor in the duration of protection. In terms of safety, the European licensed vaccines were found to be well tolerated in both children (aged 1–17 years) and adults, with local injection site reactions in 24.8% (4.3–54%) and systemic reactions in 30% (0.6–45.9%) of vaccinees. Vaccine-related serious adverse events (SAEs) were rare.

In February 2021, the U.S. FDA accepted for Priority Review Pfizer’s Biologics License Application (BLA) for TicoVac, its tick-borne encephalitis (TBE) vaccine for active immunization to prevent TBE in individuals 1 year of age and older. If approved, TicoVac would be the first vaccine in the U.S. to help protect adults and children who are visiting or living in TBE endemic areas. In line with the Priority Review designation, the FDA will target an action within six months of the application submission date, with the anticipated Prescription Drug User Fee Act (PDUFA) action date expected for August 2021.

The BLA is based on results from "more than 40 years of experience and evidence outside the U.S." In clinical trials, the safety and immunogenicity of TicoVac were assessed across two age groups (1-15 years of age and 16-65 years of age). In these studies, pooled seropositivity rates were 99-100% in 1-15 year olds and 94-99% in adults over 15 years following three doses. Clinical studies demonstrated that TicoVac was well tolerated, with no unexpected adverse events or vaccine-related serious adverse events observed. Subsequent real-world studies have shown that the vaccine is 96-99% effective in people who have received at least two doses of the vaccine, and two to three doses of the vaccine were shown to be sufficient to provide a long-lasting immune memory (Pfizer, 2021b).

On August 13, 2021, the U.S. FDA approved TicoVac (Pfizer Inc.), a tick-borne encephalitis (TBE) vaccine, for active immunization to prevent TBE in individuals 1 year of age and older. FDA approval was based on the safety and immunogenicity of TicoVac that were assessed across two age groups (Study 209: 1 to 15 years of age and Studies 213 and 690601: persons 16 years of age and older). In these studies, seropositivity rates were 99.5% in the group of 1 to 15 year olds and 98.7-100% in persons older than 15 years following three primary doses. Clinical studies demonstrated that TicoVac was generally well tolerated, with no unexpected adverse events or vaccine-related serious adverse events observed. The most common adverse reactions across both age groups were local tenderness, headache, local pain, fever, restlessness, fatigue, and muscle pain. Real-world studies from Austria have shown that the vaccine is 96-98.7% effective in people who have received at least three doses of the vaccine (Pfizer, 2021a, 2021c).

Two open-label, multi-center follow-up studies, which enrolled subjects who were seropositive 1 month after the third vaccination from Studies 213 (N=252, ages 16 through 65 at the time of the first TicoVac dose) and 209 (N=358, ages 1 through 15 at the time of the first TicoVac dose), were conducted to assess the seropersistence of TBE antibodies after completion of the primary vaccination series and the antibody response to a booster administration. Three years after the primary series of TicoVac, neutralization test (NT) seropositivity in follow-up studies 223 and 700401 ranged from 82.9% to 100% depending on age. Following a booster dose, the NT seropositivity rates were 100% (Pfizer, 2021a).

Typhoid Vaccine

Salmonella enterica serotypes Typhi, Paratyphi A, Paratyphi B (tartrate negative), and Paratyphi C cause potentially severe and occasionally life-threatening bacteremic illnesses referred to as typhoid fever (for Typhi serotype) and paratyphoid fever (for Paratyphi serotypes), and collectively as enteric fever. Other Salmonella serotypes, collectively known as nontyphoidal Salmonella, typically cause gastroenteritis as the main symptom. Typhoid and paratyphoid fever are acquired through consumption of water or food contaminated by feces of an acutely infected or convalescent person, or a person with chronic, asymptomatic carriage. The clinical presentation is often confused with malaria. Healthcare professionals should suspect enteric fever in a person with a history of travel to an endemic area who is not responding to antimalarial medication (CDC, 2025).

Typhoid vaccine is recommended for travelers 2 years and older going to areas where risk for exposure to Typhi is recognized. Vaccination offers 50 to 80% protection against disease (CDC, 2025).

The CDC’s Advisory Committee on Immunization Practices (ACIP) (2015) states that routine typhoid vaccination is not recommended in the United States but recommends vaccination for individuals at increased risk of exposure to Salmonella enterica serotype Typhi. These groups include travelers to areas with recognized typhoid risk, particularly Asia, Africa, and Latin America; persons with intimate exposure to a documented chronic Typhi carrier; and laboratory personnel routinely handling Typhi cultures or specimens. Two vaccines are licensed in the United States: a parenteral Vi capsular polysaccharide vaccine (single intramuscular dose, approved for persons ≥2 years, given ≥2 weeks before exposure) and an oral live‑attenuated Ty21a vaccine (four doses on alternating days, approved for persons ≥6 years, completed ≥1 week before exposure). Both vaccines demonstrate moderate efficacy in endemic populations, and neither vaccine is licensed for prevention of paratyphoid fever. Revaccination is recommended for ongoing exposure (every 2 years for Vi polysaccharide and every 5 years for Ty21a). Ty21a is contraindicated in immunocompromised persons and generally in pregnancy, may be affected by concurrent antimicrobial therapy, and should not be given during acute febrile or gastrointestinal illness. The Vi polysaccharide vaccine is considered theoretically safer in immunocompromised individuals. ACIP emphasizes that vaccination does not replace food and water precautions, as vaccine‑induced protection is incomplete and can be overwhelmed by high inoculum exposure. Both vaccines are generally well tolerated, with low rates of serious adverse events reported through postmarketing surveillance (Jackson et al., 2015).

Vi capsular polysaccharide vaccine (ViCPS) (Typhim Vi; Sanofi Pasteur, Inc.) consists of one 0.5 mL (25 µg) dose administered intramuscularly ≥2 weeks before travel. The vaccine is approved for use in people ≥2 years old. A dose is recommended every 2 years for those who remain at risk (CDC, 2025).

The live‑attenuated oral Ty21a typhoid vaccine (Vivotif; Bavarian Nordic A/S) is administered as a primary series of 4 enteric‑coated capsules taken every other day, with all doses required to achieve maximal efficacy. Capsules must be kept refrigerated, swallowed whole with cool liquid (≤37°C) approximately 1 hour before a meal and at least 2 hours after a prior meal, and alcohol should be avoided around dosing due to potential disruption of the enteric coating. The full series should be completed at least 1 week before potential exposure, and incomplete or improperly timed dosing may result in a suboptimal immune response, as the impact of missed or delayed doses has not been established. Ty21a is approved for use in individuals aged ≥6 years, and revaccination with the full four‑dose series is recommended every 5 years for persons who remain at ongoing risk for exposure to Salmonella serotype Typhi (CDC, 2025).

Adverse reactions most often associated with ViCPS vaccine include headache, injection-site reactions, fever, and general discomfort. Adverse reactions to Ty21a vaccine are rare and mainly consist of abdominal discomfort, diarrhea, fever, headache, nausea, vomiting, and rash (CDC, 2025).

Vaccines for Pregnant Travelers

Nasser and colleagues (2020) noted that pregnant travelers and their offspring are vulnerable to severe outcomes following a wide range of infections. Vaccine-preventable diseases can have a particularly severe course in pregnant women, but little is known about the safety of travel vaccines in pregnant women. These investigators carried out a systematic review of all published literature concerning the safety of vaccines frequently given to travelers such as yellow fever, MMR (mumps, measles and rubella), influenza, Tdap (tetanus, diphtheria and pertussis), meningococcus, hepatitis A and B, rabies, polio, typhoid fever, tick-borne encephalitis and Japanese encephalitis vaccines. They included case series, cohort studies and RCTs. For the meta-analysis, these researchers included only RCTs that compared the administration of a vaccine to placebo or to no vaccine. Outcome measures included severe systemic adverse events (AEs), maternal outcomes related to the course of pregnancy, neonatal outcomes and local AEs. They calculated the RR and its 95% CI as the summary measure. The safety of influenza vaccine is supported by high-quality evidence. For Tdap vaccine, no evidence of any harm was found in the meta-analysis of RCTs. A slight increase in chorioamnionitis rate was reported in 3 out of 12 observational studies.  However, this small possible risk is far out-weighed by a much larger benefit in terms of infant morbidity and mortality. Meningococcal vaccines are probably safe during pregnancy, as supported by RCTs comparing meningococcal vaccines to other vaccines.  Data from observational studies support the safety of hepatitis A, hepatitis B and rabies vaccines, as well as that of the live attenuated yellow fever vaccine. The authors found little or no data about the safety of polio, typhoid, Japanese encephalitis, tick-borne encephalitis and MMR vaccines during pregnancy.

Yellow Fever Vaccine Safety in Immunocompromised Individuals

Yellow fever is an acute viral hemorrhagic disease caused by yellow fever virus, a flavivirus transmitted primarily by Aedes and Haemagogus mosquitoes, and is endemic in parts of sub‑Saharan Africa and tropical South America. Clinical illness ranges from a self‑limited febrile syndrome to severe disease with jaundice, hemorrhage, and multiorgan failure, with case‑fatality rates among severe cases reported up to 20–50% in outbreaks, and there is no specific antiviral therapy, making prevention through vaccination and mosquito avoidance the main public health strategies (CDC, 2024; WHO, 2025).

According to the Centers for Disease Control and Prevention (CDC), the yellow fever vaccine is recommended for individuals aged 9 months or older who are traveling to or residing in areas at risk for yellow fever virus transmission in Africa and South America. This vaccine, which is a live, weakened virus formulation, is generally safe for most people and provides long-lasting, typically lifelong protection with a single dose, eliminating the need for routine boosters. However, travelers to regions experiencing ongoing outbreaks may consider receiving a booster if 10 years or more have elapsed since their last vaccination, and some countries mandate proof of vaccination for entry. While the CDC indicates that reactions to the vaccine are usually mild, serious adverse events can occur, including anaphylaxis, encephalitis or meningitis, Guillain-Barré syndrome, and internal organ dysfunction or failure. Precautions are advised for infants aged 6–8 months, adults over 60 years, and pregnant or breastfeeding individuals, while contraindications include severe allergies to vaccine components (such as eggs), age 6 months or younger, organ transplantation, malignant tumors, thymus disorders with abnormal immune function, primary immunodeficiency, use of immunosuppressive or immunomodulatory therapies, and symptomatic HIV infection or severe CD4+ T-lymphocyte depletion. Therefore, individuals are encouraged to consult a healthcare provider to evaluate the risks, benefits, and country-specific requirements prior to vaccination (CDC, 2024).

The Advisory Committee on Immunization Practices (ACIP) provided the following yellow fever vaccine booster dose recommendations (Staples et al., 2015):

• Primary vaccination - A single primary dose provides long‑lasting protection and is adequate for most travelers. Booster dose not recommended [Category A]
• Booster dose for certain travelers:
  
  
  • Women vaccinated while pregnant should receive 1 additional dose before their next travel that puts them at risk for yellow fever virus infection [Category A]
  • Persons who received a hematopoietic stem cell transplant after prior vaccination should be revaccinated if immunocompetent and at risk [Category A]
  • Persons infected with human immunodeficiency virus (HIV) at the time of last vaccination should receive a dose every 10 years if they remain at risk [Category A]
    
    
• Booster dose may be considered for travelers vaccinated ≥10 years ago who will be in higher‑risk settings (e.g., prolonged travel, rural West Africa, peak transmission season, ongoing outbreaks) [Category B]
• Laboratory workers who routinely handle wild-type yellow fever virus should have yellow fever virus–specific neutralizing antibody titers measured at least every 10 years to determine if they should receive additional doses of the vaccine. For laboratory workers who are unable to have neutralizing antibody titers measured, yellow fever vaccine should be given every 10 years as long as they remain at risk [Category A].

de Araujo Lagos et al. (2023) stated that yellow fever (YF) is an arbovirus with variable severity, including severe forms with high mortality, and vaccination is the most effective measure to protect against the disease. Non-serious and serious adverse events (AEs) have been described in immunocompromised individuals; however, previous studies have failed to show this association. In a systematic review, these investigators examined the risk of AEs following YF vaccination in immunocompromised individuals compared with its use in non-immunocompromised individuals. They carried out a literature search in the Medline, LILACS, Embase, SCOPUS, DARE, Toxiline, Web of Science, and grey literature databases for publications until February 2021. Randomized and quasi-randomized clinical trials and observational studies that included immunocompromised subjects (individuals with HIV infection, organ transplantation, cancer, those using immunosuppressive drugs for rheumatologic diseases, and those on immunosuppressive therapy for other diseases) were selected. The methodological quality of observational or non-randomized studies was assessed using the ROBINS-I tool. These researchers conducted two meta-analyses, proportion and risk factor analyses, to identify the summary measure of risk ratio (RR) in the studies that had variables suitable for combination. A total of 25 studies were included, most with a risk of bias classified as critical; 13 studies had enough data to perform the proposed meta-analyses. Seven studies without a comparator group had their results aggregated in the proportion meta-analysis, identifying an 8.5% (95% CI: 0.07 to 21.8) risk of immunocompromised individuals presenting AEs following vaccination. Six cohort studies were combined, yielding an RR of 1.00 (95% CI: 0.78 to 1.29). Subgroup analysis was conducted according to the etiology of immunosuppression and was also unable to identify an increased risk of AEs following vaccination. The authors concluded that it was not possible to affirm that immunocompromised individuals, regardless of etiology, had a higher risk of AEs following the YF vaccine.

Schnyder et al. (2024) noted that long-term immunity following yellow fever vaccination remains controversial. In a systematic review and meta-analysis, these investigators examined the available evidence regarding the long-term protection (10 years or longer) conveyed by a single dose of yellow fever vaccination. They searched 11 databases from their inception to August 24, 2023. These researchers included cohort and cross-sectional studies reporting immunogenicity outcomes for children or adults who received a single dose of yellow fever vaccination 10 or more years ago. Case series and single case reports were excluded. Participants who received more than one dose of yellow fever vaccination before measurement of the outcome were also excluded. Identified records were reviewed by two independent reviewers. The primary outcome of the meta-analysis was the pooled sero-protection rate. Risk of bias was assessed with the Risk Of Bias In Non-randomized Studies of Interventions tool and the Joanna Briggs Institute tool for analytical cross-sectional studies. Studies of moderate or good quality that reported sero-protection were included for random-effects meta-analysis and stratified by endemicity and specific risk groups. Of the 7,363 articles identified by the search, 39 were eligible for inclusion in the systematic review. These studies comprised 2,895 individuals vaccinated 10 to 60 years ago. A total of 20 studies were included in the meta-analysis. Pooled sero-protection rates were 94% (95% CI: 86 to 99) among healthy adults in a non-endemic setting (mostly travelers) and 76% (65 to 85) in an endemic setting (all Brazilian studies). The pooled sero-protection rate was 47% (35 to 60) in children (aged 9 to 23 months at the time of vaccination) and 61% (38 to 82) in individuals living with HIV. Reported criteria for sero-protection were highly heterogeneous. The authors concluded that the gathered evidence suggested that a single dose of yellow fever vaccination provided lifelong protection in travelers; however, in individuals living with HIV and children (younger than 2 years), booster doses might still be needed because lower proportions of vaccinees were sero-protected 10 or more years post-vaccination. Lower observed sero-protection rates among residents of endemic areas were partly explained by the use of a higher cut-off for sero-protection that was applied in Brazil. Studies from sub-Saharan Africa were scarce and of low quality; therefore, no conclusions could be drawn for this region.

YF‑VAX (yellow fever vaccine, live) is a subcutaneous vaccine indicated for active immunization against yellow fever in persons 9 months of age and older who live in or travel to endemic areas, transit through countries with yellow fever transmission, or who may be required to present a valid International Certificate of Vaccination or Prophylaxis, as well as laboratory personnel at risk of exposure to yellow fever virus. It is contraindicated in individuals with a history of acute hypersensitivity to any vaccine component, including eggs or egg products, infants younger than 9 months, lactating women providing breastmilk to infants under 9 months, and persons with severe immunosuppression, including thymic disorders associated with abnormal immune function. Severe allergic reactions, including anaphylaxis, may occur, and medical treatment must be available. Age greater than 60 years is a risk factor for yellow fever vaccine–associated viscerotropic disease and neurotropic disease, which have occurred primarily after first vaccination; therefore, vaccination in older adults requires careful risk–benefit assessment. The vaccine may not protect 100% of recipients, syncope can occur following vaccination, data on interactions with other vaccines are limited, immunogenicity may be reduced in individuals receiving systemic corticosteroids or with asymptomatic HIV infection, and use during pregnancy or breastfeeding should be considered only if clearly needed because of potential risks to infants (Sanofi Pasteur, 2025).

Zaire Ebolavirus Vaccine

The Ebola virus [Zaire ebolavirus (EBOV)] vaccine is a replication-competent, live, attenuated recombinant vesicular stomatitis virus (rVSV) vaccine. It contains a gene from the Ebola virus, not the whole virus, which means that persons cannot become infected with EBOV from the vaccine. The vaccine is known as rVSVΔG-ZEBOV-GP Ebola vaccine, with the brand name Ervebo (manufactured by Merck). The vaccine was approved by the U.S. FDA on December 19, 2019, for the prevention of Ebola virus disease (EVD) caused by EBOV in people 18 years of age and older, based on data from 12 clinical trials that included a total of 15,399 adults (CDC, 2021).

Study 3 (Ring vaccination study) was an open-label, randomized cluster (ring) vaccination study conducted in the Republic of Guinea during the 2014 outbreak. Each cluster was composed of contacts and contacts of contacts of individuals with laboratory-confirmed Ebola virus disease (EVD). Clusters were randomized to receive either an “immediate” vaccination or a 21-day “delayed” vaccination. In the primary efficacy analysis, 3,537 subjects aged 18 years and older were considered contacts and contacts of contacts of an index case with laboratory-confirmed EVD. Of these, 2,108 were included in 51 immediate vaccination clusters, and 1,429 were included in 46 delayed vaccination clusters. In the primary efficacy analysis, the number of cases of laboratory-confirmed EVD in subjects vaccinated in immediate vaccination clusters was compared to the number of cases in subjects in delayed vaccination clusters. Cases of EVD that occurred between Day 10 and Day 31 post-randomization of the cluster were included in the analysis. Vaccine efficacy was 100%; no cases of confirmed EVD were observed in the immediate vaccination clusters, and 10 confirmed cases of EVD were observed in a total of 4 delayed vaccination clusters between Day 10 and Day 31 post-randomization (Merck, 2019).

On February 26, 2020, the Advisory Committee on Immunization Practices (ACIP) recommended pre-exposure vaccination with Ervebo® for adults aged 18 years or older in the U.S. population who are at potential risk of exposure to EBOV. This recommendation includes adults who are responding or may respond to an outbreak of EVD; laboratorians or other staff working at biosafety-level 4 facilities in the United States; or healthcare personnel (HCP) working at federally designated Ebola Treatment Centers in the United States. HCP refers to all paid and unpaid persons serving in healthcare settings who have the potential for direct or indirect exposure to patients or infectious materials, including body substances (e.g., blood, tissue, and specific body fluids); contaminated medical supplies, devices, and equipment; contaminated environmental surfaces; or contaminated air. These HCP include, but are not limited to, emergency medical service personnel, nurses, nursing assistants, physicians, technicians, clinical laboratory personnel, autopsy personnel, therapists, phlebotomists, pharmacists, students and trainees, contractual staff not employed by the healthcare facility, and persons not directly involved in patient care but who could be exposed to infectious agents that can be transmitted in the healthcare setting (e.g., clerical, dietary, environmental services, laundry, security, engineering and facilities management, administrative, billing, and volunteer personnel) (CDC, 2021).

Ervebo (Merck Sharp & Dohme Corporation) is a vaccine indicated for the prevention of disease caused by Zaire ebolavirus in individuals 18 years of age and older. Immunization with Ervebo results in an immune response and protection from disease caused by Zaire ebolavirus. The relative contributions of innate, humoral and cell-mediated immunity to protection from Zaire ebolavirus are unknown.

Limitations of use include:

• The duration of protection conferred by Ervebo is unknown;
• Ervebo does not protect against other species of Ebolavirus or Marburgvirus;
• Effectiveness of the vaccine when administered concurrently with antiviral medication, immune  globulin (IG), and/or blood or plasma transfusions is unknown.

Ervebo is available as 1 mL suspension for injection supplied as a single-dose vial and is to be administered intramuscularly.

Ervebo label carries warnings and precautions for anaphylaxis. Vaccinated individuals should continue to adhere to infection control practices to prevent Zaire ebolavirus infection and transmission. Vaccine virus RNA has been detected in blood, saliva, urine, and fluid from skin vesicles of vaccinated adults; transmission of vaccine virus is a theoretical possibility. The most common injection-site adverse events were injection-site pain (70%), swelling (17%), and redness (12%). The most common systemic adverse events reported were headache (37%), feverishness (34%), muscle pain (33%), fatigue (19%), joint pain (18%), nausea (8%), arthritis (5%), rash (4%) and abnormal sweating (3%) (Merck, 2019).

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