Meningococcal Vaccine

Number: 0356

Policy

1. Aetna considers meningococcal vaccine a medically necessary preventive service according to the recommendations of the Centers for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practices (ACIP).

   The ACIP recommends immunization with meningococcal vaccine of all adolescents 11 through 18 years of age followed by a one-time booster dose of the vaccine 5 years later through age 21 years.

   The ACIP also recommends meningococcal immunization for persons with one or more of the following risk factors:

   1. Anatomic asplenia (surgical or congenital);
   2. College freshmen living in dormitories if they haven't been vaccinated since they were 16 years of age;
   3. Functional asplenia (sickle-cell disease);
   4. HIV infected adults;
   5. Microbiologists who are routinely exposed to isolates of N. meningitidis;Footnotes*
   6. Military recruits;Footnotes*
   7. Persons who are traveling to countries in which N. meningitidis is hyperendemic or epidemic, particularly if contact with the local population will be prolonged;Footnotes* or
   8. Persons with persistent complement component deficiencies.

   Revaccination at 5-year intervals indefinitely is considered medically necessary for persons who remain in one of these increased risk groups.

2. Aetna considers unconjugated meningitis vaccine (Menomune, Sanofi Pasteur, Swiftwater, PA) an acceptable alternative to conjugated meningitis vaccine (Menactra, Sanofi Pasteur, Swiftwater, PA; Menveo, GSK Vaccines, Research Triangle Park, NC) for medically necessary indications.

3. Aetna considers meningococcal vaccine medically necessary for solid organ transplant recipients.

4. An age-appropriate meningococcal vaccine that includes serogroups A and W is indicated for travelers to areas with high endemicity (parts of sub-Saharan Africa or the Hajj in Saudi Arabia).

5. Aetna considers meningococcal group B vaccine (Trumenba, Bexsero) medically necessary to prevent invasive disease caused by Neisseria meningitidis serogroup B in individuals 10 years of age and older according to the recommendations of the Centers for Disease Control and Preventions (CDC) Advisory Committee on Immunization Practices (ACIP).

   The ACIP recommends serogroup B meningococcal vaccination for people aged 10 years and older at elevated risk for meningococcal disease. This includes:

   • People with persistent complement component deficiencies;
   • People with anatomic or functional asplenia;
   • Persons on a complement inhibitor (e.g., Soliris, Berinert, Cinryze);
   • Microbiologists who are regularly exposed to Neisseria meningitidisFootnotes*; or
   • People at increased risk owing to an outbreak of serogroup B meningococcal disease.
     

   The ACIP also states that serogroup B meningococcal vaccination series may be administered to adolescents and young adults 16 through 23 years of age to provide short term protection against most strains of group B meningococcus.

6. Aetna considers meningococcal vaccine experimental and investigational for all other indications because of insufficient evidence in the peer-reviewed literature.

7. Aetna considers the use of saliva testing of antibody levels against meningococcal serogroups for monitoring meningococcal vaccine responses experimental and investigational because the effectiveness of this approach has not been established.

Note: MenHibrix® [Meningococcal Groups C and Y and Haemophilus b Tetanus Toxoid Conjugate Vaccine] was discontinued in the U.S in 2016 (GSK, 2016).

Footnotes*Note: Some plans exclude coverage of immunizations for travel or work. Please check benefit plan descriptions for details.

Background

Meningococcal meningitis, caused by the bacterium Neisseria meningitidis, is a potentially fatal bacterial infection that afflicts between 2500 and 3000 persons in the United States each year. Approximately 10 percent of individuals who contract meningococcal disease will die. Of survivors, up to one in five suffer long-term permanent disabilities such as hearing loss, brain damage and limb amputations.

Advisory Committee on Immunization Practices (ACIP) currently recommends tetravalent or quadrivalent meningococcal conjugate vaccine for all 11 to 18 year olds and for persons aged 2 to 55 years who are at increased risk for meningococcal disease (CDC, 2007, 2010). The previous recommendations for meningococcal conjugate vaccine administration consisted of three cohorts: 11 to 12 year olds, adolescents entering high school (or 15 year olds), and other persons at increased risk for meningococcal disease, such as incoming college freshmen who would be living in dormitories. Because many adolescents do not see a doctor regularly, the expanded recommendations allow physicians to vaccinate adolescent patients whenever the opportunity to do so arises. The revised recommendations continue to emphasize that 11 to 12 year olds should receive the meningococcal conjugate vaccine at the 11 to 12 year old preventive care visit, along with other routine adolescent vaccinations.  The ACIP has stated that their goal is routine vaccination of all adolescents beginning at age 11 years.

Adolescents and young adults in particular are at increased risk of contracting meningococcal meningitis because of certain lifestyle factors, such as crowded living conditions, moving to a new residence, attending a new school with students from geographically diverse areas, sharing beverages or utensils, going to bars, active or passive smoking, and irregular sleeping patterns (NMA, 2004). A CDC study of 83 reported meningitis cases in college students from September 1998 through May 1999, a rate of 1.4 cases per 100,000 freshmen, and 3.8 cases per 100,000 freshmen living in dormitories. The rate for all 18 to 22 year olds was 1 case per 100,000. According to the American College Health Association, between 100 and 125 college students get meningitis each year, and up to 10 die. Routine vaccination with meningococcal vaccine is also recommended for other populations at increased risk (i.e., military recruits, travelers to areas in which meningococcal disease is hyperendemic or epidemic, microbiologists who are routinely exposed to isolates of N. meningitidis, patients with anatomic or functional asplenia, and patients with terminal complement deficiency).

A conjugate vaccine is developed by attaching a polysaccharide antigen to a carrier protein in order to enhance the body's immune response to the vaccine.  There are 2 meningococcal conjugate vaccines approved by the United States (U.S.) Food and Drug Administration (FDA):

1. meningococcal [Groups A, C, Y and W-135] polysaccharide diphtheria toxoid conjugate (Menactra, Sanofi Pasteur Inc., Swiftwater, PA),  a purified meningococcal polysaccharide conjugated with an diphtheria toxin in order to prolong the immunogenic effect of the vaccine, and
2. meningococcal [Groups A, C, Y, and W-135] oligosaccharide diphtheria CRM₁₉₇ conjugate vaccine (Menveo, Novartis Vaccines and Diagnostics, Inc., Cambridge, MA), which is similar to Menactra. Whereas standard unconjugated meningitis vaccine (i.e., Menomune meningococcal [Groups A, C, Y and W-135] polysaccharide vaccine (Sanofi Pasteur Inc.) induces protective immunity for three to four years, conjugated meningitis vaccines are expected to provide protective immunity for up to eight years.

Both Menactra and Menomune are currently approved by the U.S. Food and Drug Administration (FDA) for persons aged 2 years and older. The FDA approved Menactra for use in children aged 2 to 10 years on October 17, 2007, in addition to its prior approval for use in persons aged 11 to 55 years. Menveo was approved by the FDA on February 19, 2010 for use among persons aged 11 to 55 years. Previous ACIP recommendations called for vaccination with Menomune for children aged 2 - 10 years who are at increased risk for meningococcal disease.  However, ACIP revised its recommendation during its October 24, 2007 meeting to state that meningococcal conjugate vaccine is preferable to meningococcal polysaccharide vaccine for vaccination of children aged 2 - 10 years who are at increased risk for meningococcal disease. Menactra and Menveo are administered intramuscularly, while Menomune is administered subcutaneously. Generally, only a single dose of meningococcal vaccine is indicated. 

The Advisory Committee on Immunization Practices states that revaccination may be indicated for persons previously vaccinated with meningococcal vaccine who remain at high risk for infection (i.e., those with terminal complement deficiencies, with anatomic or functional asplenia, travelers to hyperendemic or epidemic areas), particularly for children who were first vaccinated when they were less than 4 years of age.  According to the ACIP, such children should be considered for revaccination after 2 to 3 years if they remain at high risk. For children aged 2 -10 years who have previously received meningococcal polysaccharide vaccine and remain at increased risk for meningococcal disease, ACIP recommends vaccination with meningococcal conjugate vaccine at 3 years after receipt of meningococcal polysaccharide vaccine. Children who last received meningococcal polysaccharide vaccine more than 3 years ago and remain at risk for meningococcal disease should be vaccinated with meningococcal conjugate vaccine as soon as possible.  In addition, adolescents 11 through 18 years of age who routinely received the meningococcal vaccine should receive a one-time booster dose 5 years later through age 21 years. Current evidence suggests that most adolescents are not protected for more than 5 years after vaccination, which is a shorter time frame than was thought when initial reccomendations were made (Hitt, 2010).  Although the need for revaccination in adults has not been determined, antibody levels decline rapidly over 2-3 years after the polysaccharide vaccine is given, and if indications still exist for vaccination, revaccination may be considered within 3-5 years. Meningitis vaccine should be administered to college freshman living in residents halls if they haven't been vaccinated since they were 16 years of age. Routine revaccination of college students who were vaccinated as freshmen is not indicated.  Revaccination of military recruits is only indicated when military personnel are traveling to countries in which N. meningitidis is hyperendemic or epidemic.

In a single, randomized, modified double-blind, controlled study of healthy U.S. children aged 2 to 10 years that compared meningococcal conjugate vaccine with meningococcal polysaccharide vaccine, serum bactericidal antibody geometric mean titers against all four serogroups were significantly higher at both 28 days and 6 months after vaccination in the children who received meningococcal conjugate vaccine. In the same study, rates of most solicited local and systemic adverse events after vaccination with meningococcal conjugate vaccine were comparable to rates observed after vaccination with meningococcal polysaccharide vaccine (Pichichero et al, 2005). It is anticipated that more data will become available within the next 5 years to guide recommendations on revaccination for persons who were previously vaccinated with meningococcal polysaccharide vaccine.

Meningococcal vaccine is contraindicated in persons with allergy to vaccine components and persons with acute, moderate or severe illnesses with or without fever. Persons with moderate or severe illness should be immunized as soon as they have recovered from the acute phase of the illness. Minor illnesses (e.g., upper respiratory tract infection, allergic rhinitis) with or without fever should not contraindicate the use of meningococcal vaccine.

The Surgical Infection Society (Howdieshell et al, 2006) stated that there are limited data on the use of vaccines after injury. In particular, the recommendations that all persons (aged 2 to 64 years) who have undergone splenectomy, should receive 23-valent pneumococcal vaccine and meningococcal vaccine, with Haemophilus influenzae type B vaccine administered to high-risk patients as well are grade D (very low quality recommendations). 

At its February 2008 meeting, the ACIP decided not to recommend routine vaccination of children aged 2 to10 years against meningococcal disease unless the child is at increased risk for the disease. The ACIP recommends routine vaccination against meningococcal disease for all persons aged 11 to 18 years followed by a one-time booster dose of the vaccine 5 years later through age 21 years and those persons aged 2 to 55 years who are at increased risk for meningococcal disease.

In 2011, the ACIP recommended use of meningococcal vaccine in infants age 9 through 23 months at increased risk of meningococcal diseases. The ACIP recommended that specific groups of children aged 9-23 months at increased risk for meningococcal disease receive a two-dose series of meningococcal vaccine taken 3 months apart:

• Infants needing protection prior to traveling or moving to an area where meningococcal disease is epidemic or highly endemic. Travelers can receive their two doses 2 months apart to accommodate travel schedules.
• Infants with complement component deficiencies such as C3, C5-9, properdin, factor H, and factor D deficiencies.
• Infants in a defined risk group for a community or institutional outbreak.
• Infants with HIV, if another indication for vaccination exists.

A 2-dose series is required for any child whose first dose was received prior to their second birthday. Those who remain at risk for meningococcal disease should receive a booster dose 3 years after the primary series.

In October, 2012 ACIP voted to recommend that infants at increased risk for meningococcal disease should be vaccinated with 4 doses of HibMenCY at 2, 4, 6, and 12 through 15 months. These include infants with recognized persistent complement pathway deficiencies and infants who have anatomic or functional asplenia including sickle cell disease. HibMenCY can be used in infants ages 2 through 18 months who are in communities with serogroup C and Y meningococcal disease outbreaks.  ACIP noted that meningococcal disease incidence has declined to historically low levels since the last peak in disease in the late 1990s and about 50 of infant cases are potentially preventable by available vaccines. The revised recommendations allow for the fact that the majority of infant cases are caused by a type of the bacteria that are not prevented by meningococcal vaccines. Also, the recommendations note that the majority of infant cases occur within the first 6 months of life, which is the time period before a vaccine would likely be able to protect the infant as 3 doses are needed (at 2, 4 and 6 months) to maximize the immune response.

At its October 2012 meeting, the ACIP voted to recommend vaccination against meningococcal serogroups C and Y for children aged 6 weeks through 18 months at increased risk for meningococcal disease.  Meningococcal groups C and Y and Haemophilus b tetanus toxoid conjugate vaccine (Hib-MenCY-TT [MenHibrix, GlaxoSmithKline Biologicals]) is licensed for active immunization for prevention of invasive disease caused by Haemophilus influenzae type b (Hib) and meningococcal serogroups C and Y.  Hib-MenCY-TT is not indicated for prevention of disease caused by meningococcal serogroup B, the most common serogroup causing disease in infants, or serogroups W135 or A, which are represented in quadrivalent meningococcal vaccines.  Before licensure of Hib-MenCY-TT, no meningococcal conjugate vaccine was licensed for infants aged 2 through 8 months.  MenACWY-D (Menactra, Sanofi Pasteur) is licensed as a 2-dose series for infants and toddlers aged 9 through 23 months, and MenACWY-D and MenACWY-CRM (Menveo, Novartis Vaccines) are licensed for persons aged 2 through 55 years as a single dose.  These vaccines are recommended routinely for persons aged 11 through 18 years and persons aged 2 through 55 years at increased risk for meningococcal disease (and persons aged 9 months through 55 years for MenACWY-D) (CDC, 2013)

Hale and colleagues (2014) reviewed the immunogenicity and safety of Hib-MenCY-TT for infants and toddlers.  Studies conducted in humans and limited to publication in English were identified through a MEDLINE (January 2000 to September 2013) search using the terms Hib-MenCY-TT, MenHibrix, and Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine.  Clinical trial registries, Web sites, and reference citations from publications identified were reviewed for additional sources.  Randomized controlled trials were included to evaluate the safety and immunogenicity of Hib-MenCY-TT.  Epidemiological data and recommendations from the ACIP were also reviewed.  Hib-MenCY-TT is available for primary vaccination of infants as a 4-dose series at 2, 4, 6, and 12 to 15 months of age.  Hib-MenCY-TT has comparable immunogenicity to licensed Hib vaccines and produces high levels of N meningitidis antibodies against serogroups C and Y.  The most common adverse events were pain and redness at the injection site, drowsiness, and irritability.  The authors concluded that Hib-MenCY-TT has been demonstrated to be a safe and immunogenic vaccination for prevention of disease caused by N meningitidis serogroups C and Y and H influenzae type b in healthy infants and toddlers.  Currently, the ACIP recommends the use of Hib-MenCY-TT specifically in high-risk infants aged 6 weeks to 18 months.  Hib-MenCY-TT provides the first therapeutic option for vaccination of infants as young as 6 weeks of age who are at increased risk for meningococcal disease.

In October 2016, GlaxoSmithKline (GSK) issued a letter to the customer regarding the decision to discontinue the manufacture and sale of MenHibrix® [Meningococcal Groups C and Y and Haemophilus b Tetanus Toxoid Conjugate Vaccine] in the US. This decision was made due to low demand for the vaccine and the resulting opportunity to shift GSK vaccine production capacity to other GSK vaccines with greater customer demand. MenHibrix continued to be available to order through February 2017 or until inventory levels were depleted (whichever occured first), at which point, GSK discontinued availability of the vaccine (GSK, 2016).

On August 1, 2014 the American Academy of Pediatrics (AAP) published updated recommendations on the use of meningococcal vaccines.  These recommendations include a statement that an age-appropriate meningococcal conjugate vaccine is preferred to the meningococcal polysaccharide vaccine for the pediatric population, unless there is a contraindication for the meningococcal conjugate vaccine.  The recommendations also state that adolescents should be routinely immunized at 11 to 12 years of age and given a booster dose at 16 years of age with a quadrivalent conjugated meningococcal vaccine; adolescents who received their first dose at age 13 to 15 years should receive a booster at age 16 to 18 years at least 8 weeks or up to 5 years after their first dose and adolescents who receive their first dose of meningococcal conjugate vaccine at or after 16 years of age do not need a booster dose.  However, the recommendations also specify that unvaccinated or previously vaccinated first-year college students through age 21 years living in residence halls who received their last dose before their 16^th birthday should receive a single dose of quadrivalent meningococcal conjugate vaccine (Committee on Infectious Diseases, 2014).

The August, 2014 AAP recommendations also list recommendations for individuals who are at increased risk for invasive meningococcal disease  because of complement disease or asplenia indicating that they should receive a 2-dose primary series (MenACWY-CRM or Hib-MenCY-TT) between 2 to 18 months of age.  The recommendations specify that MenACWY-D can be administered as a 2-dose series to infants 9 to 23 months of age in children with complement component deficiency and in infants up to 23 months of age after the fourth dose of the primary pneumococcal conjugate vaccine in children with asplenia.  The AAP recommends that HIV-infected children 11 years of age or older should receive a 2-dose primary series 8 to 12 weeks apart with a single booster dose, consistent with healthy adolescent recommendations (Committee on Infectious Diseases, 2014). 

For children greater than 2 years with persistent risk for meningogoccal disease due to asplenia or complement component deficiency, the primary series should be given including 2 doses of quadrivalent meningogoccal conjugate vaccine 8 to 12 weeks apart and for children 2 months to 6 years of age, a booster dose at 3 years after the primary series and every 5 years thereafter.  For children 7 years of age and older as well as adoescents who are at persistent risk for meningogoccal disease and who received an initial meningogoccal vaccination on or after age 7, boosters of quadrivalent meningogoccal conjugate should be repeated every 5 years.  Travelers to areas with high meningococcal endemicity should receive an age-appropriate meningococcal vaccine that includes serigroups A and W.  Areas of high endemicity include the ‘meningitis belt’ of sub-Saharan Africa and the Hajj in Saudi Arabia (Committee on Infectious Diseases, 2014).

Hib-MenCY-TT may be co-administered with other routine infant vaccinations, including 13-valent pneumococcal conjugate vaccine. Hib-MenCY-TT should not be co-administered with other Hib-containing vaccines (Rubin et al, 2013).

The ACIP (2017) recommends that HIV-infected adults should receive two doses of serogroups A, C, W, and Y meningococcal conjugate vaccine. 

Trumenba was approved by the FDA via the accelerated approval regulatory pathway was annouced October 2014 by the U.S. Food and Drug Administration (FDA).  Trumemba is licensed in the United States to prevent invasive meningococcal disease caused by Neisseria meningotidis serogroup B in individuals 10 to 25 years of age (FDA, 2014). 

The FDA announced that three randomized studies that were conducted in the United states and Europe in approximately 2,800 adolescents showed that after vaccination, 82 percent had antibodies against four different  serogroup B strains compared with less than 1 percent before vaccination (FDA, 2014). The effectiveness of Trumenba against diverse serogroup B strains has not been confirmed (Pfizer, 2015).

The safety of Trumenba was assessed in approximately 4,500 patients who received the vaccine in studies conducted in the United States, Europe, and Australia, in which the most commonly reported side effects were pain and swelling at the injection site, headache, diarrhea, muscle pain, joint pain, fatigue and chills (FDA, 2014). Individuals with weakened immune systems may have a reduced immune response (Pfizer, 2015).

Trumenba is administered via intramuscular injection as a 3 dose series according to a  0, 2, and 6 month schedule (Wyeth, 2014).

The FDA granted accelerated approval of Bexsero (meningococcal group B Vaccine [recombinant, adsorbed]) for active immunization to prevent invasive meningococcal disease caused by serogroup B in adolescents and young adults from 10 years through 25 years of age (Novartis, 2015). As part of the accelerated approval process, the manufacturer will complete its ongoing studies to confirm the effectiveness of Bexsero against diverse serogroup B strains. 

In phase II and phase III studies, Bexsero demonstrated a protective immune response in adolescents and young adults after two doses. Approval of Bexsero is based on demonstration of immune response, as measured by serum bactericidal activity against three serogroup B strains representative of prevalent strains in the United States. The effectiveness of Bexsero against diverse serogroup B strains has not been confirmed (Novartis, 2015).

Three studies evaluating Bexsero’s effectiveness were conducted in Canada, Australia, Chile, and the United Kingdom in approximately 2,600 adolescents and young adults (FDA, 2015). Among study participants who received two doses of Bexsero, after vaccination, 62 to 88 percent had antibodies in their blood that killed three different N. meningitidis serogroup B strains in tests carried out in a laboratory, compared with 0 to 23 percent before vaccination. These three strains are representative of strains that cause serogroup B meningococcal disease in the U.S. 

The safety of Bexsero was assessed in approximately 5,000 participants who received the vaccine in studies conducted in the U.S. and abroad (FDA, 2015). The most commonly reported side effects by those who received Bexsero were pain and swelling at the injection site, headache, diarrhea, muscle pain, joint pain, fatigue, and chills.

The tolerability profile of Bexsero was also demonstrated as part of a CDC-sponsored clinical trial conducted in approximately 15,000 individuals at Princeton University and the University of California, Santa Barbara (UCSB) during meningitis B outbreaks on these college campuses (Novartis, 2015). The safety data from the CDC clinical trial are consistent with results observed in previous studies.

Bexsero is administered in two intramuscular doses (0.5 ml each) administered at least one month apart (Novartis, 2015).

Data are not available on the safety and effectiveness of using Trumenba and other Bexsero meningococcal group B vaccines interchangeably to complete the vaccination series (Pfizer, 2015).

The ACIP (2015) recommends serogroup B meningococcal vaccination for people aged 10 years and older at elevated risk for meningococcal disease. This includes:

• people with persistent complement component deficiencies;
• patients with anatomic or functional asplenia;
• microbiologists who are regularly exposed to Neisseria meningitidis; or
• people at increased risk owing to an outbreak of serogroup B meningococcal disease.

The ACIP (2015) also states that patients and clincians may choose to administer serogroup B meningococcal vaccine to all persons between ages 16 through 23 years. The approved recommendation states, "A serogroup B meningococcal (MenB) vaccine series may be administered to adolescents and young adults 16 through 23 years of age to provide short term protection against most strains of serogroup B meningococcal disease. The preferred age for MenB vaccination is 16 through 18 years of age." The recommendation is labeled as "Category B," meaning that individual clinical decision-making is recommended.

The ACIP (2016) concluded that meningitis vaccine (e.g., Menactra) should be administered to college freshman living in residents halls if they haven't been vaccinated since they were 16 years of age. ACIP determined that HIV is not an indication for routine vaccination with meningococcus quadrivalent or type B vaccine.

Beeslaar and colleagues (2018) stated that invasive meningococcal disease (IMD) caused by Neisseria meningitidis is a potentially devastating condition that can result in death and is associated with serious long-term sequelae in survivors.  Vaccination is the preferred preventative strategy.   Quadri-valent polysaccharide-based vaccines that protect against infection caused by meningococcal serogroups A, C, W, and Y are not effective against meningococcal serogroup B (MenB), which was responsible for approximately 60 % and 35 % of confirmed IMD cases in the European Union (EU) and the U.S. in 2016, respectively.  A recombinant protein MenB vaccine (MenB-FHbp [bivalent rLP2086; Trumenba®]) has been approved for protection against MenB infection in persons 10 to 25 years of age in the U.S. and Canada and for individuals greater than or equal to 10 years of age in the EU and Australia.  In these regions, MenB-FHbp is approved as a 2- or 3-dose primary vaccination schedule.  These investigators reviewed the current evidence supporting administration of MenB-FHbp as a 2-dose primary vaccination schedule.  They also reviewed different contexts in which a 2- or 3-dose primary vaccination schedule might be preferred (e.g., routine prospective vaccination versus outbreak control).

The CDC (2020) released an updated schedule for adult vaccines including those for meningitis B.  It states that "Individuals aged 10 years or older who have complement deficiency, who use a complement inhibitor, who have asplenia, or who are microbiologists should receive a meningitis B vaccine dose 1 year following completion of a primary series.  After that, they should receive booster doses every 2 to 3 years for as long they are at elevated risk".

Use of Saliva Testing of Antibody Levels Against Meningococcal Serogroups for Monitoring Meningococcal Vaccine Responses

van Ravenhorst and associates (2018) noted that meningococcal infection starts with colonization of the upper respiratory tract.  Mucosal immunity is important for protection against acquisition and subsequent meningococcal carriage.  In this study, these researchers evaluated salivary antibody levels against meningococcal serogroup A (MenA), W (MenW) and Y (MenY) after vaccination with a quadri-valent MenACWY conjugated vaccine.  They also compared salivary meningococcal serogroup C (MenC) antibody levels after monovalent MenC and quadri-valent MenACWY conjugated vaccination.  Healthy participants, who had received MenC conjugate vaccine between 14 months and 3 years of age, received a (booster) MenC or MenACWY vaccination at age 10 to 15 years.  MenA-, MenC-, MenW- and MenY-polysaccharide (PS) specific IgG and IgA levels in saliva and serum and PS specific secretory component levels in saliva were measured using the fluorescent-bead-based multiplex immunoassay.  MenACYW vaccination increased salivary PS-specific IgA (2-fold) and IgG levels(greater than 10-fold) for MenA, MenY, and MenW.  After 1 year, salivary IgA levels had returned to baseline levels.  Both vaccines induced an increase in salivary MenC-PS specific IgA (greater than 3-fold) and IgG (greater than 100-fold), with higher levels after MenC as compared to MenACWY vaccination.  The antibody decay rate of MenC in saliva between 1 month and 1 year was similar for both vaccines.  The overall correlation between serum and saliva IgA levels was low (R = 0.39, R = 0.58, R = 0.31, and R = 0.36 for MenA, MenC, MenW and MenY, respectively).  Serogroup-PS specific IgG levels between serum and saliva correlated better (R ranged from 0.51 to 0.88).  The authors concluded that both primary and booster parenteral meningococcal conjugate vaccination induced antibody levels in saliva for all targeted sero-groups.  These investigators stated that salivary samples might be an interesting screening tool to measure vaccine responses after both primary and booster vaccination, especially in geographical areas where blood collection is challenging.  They noted that while a minimal threshold needs yet to be assessed, IgG antibodies in saliva samples could potentially serve as surrogate of protection.

van Ravenhorst and colleagues (2019) stated that mucosal antibodies against capsular polysaccharides offer protection against acquisition and carriage of encapsulated bacteria like Neisseria meningitidis serogroup C.  Measurements of salivary antibodies as replacement for blood testing has important (cost-effective) advantages, especially in studies that evaluate the impact of large-scale vaccination or in populations in which blood sampling is difficult.  These researchers estimated a threshold for meningococcal IgG salivary antibody levels to discriminate between unprotected and protected vaccinated individuals.  MenA-, MenC-, MenW- and MenY- PS specific IgG levels in serum and saliva from participants in a meningococcal vaccination study were measured using the fluorescent-bead-based multiplex immunoassay.  Functional antibody titers in serum against the 4 serogroups were measured with serum bactericidal assay using rabbit complement (rSBA).  A threshold for salivary IgG was determined by analysis of receiver operating characteristic (ROC) curves using a serum rSBA titer of greater than or equal to 128 as correlate of protection.  The area under the curve (AUC) was calculated to quantify the accuracy of the salivary test and was considered adequate when greater than or equal to 0.80.  The optimal cut-off was considered adequate when salivary IgG cut-off levels provided specificity of greater than or equal to 90 %.  True positive rate (sensitivity), positive predictive value (PPV), and negative predictive value (NPV) were calculated to explore the possible use of salivary antibody levels as a surrogate of protection.  The best ROC curve (AUC of 0.95) was obtained for MenC, with an estimated minimum threshold of MenC-PS specific salivary IgG greater than or equal to 3.54 ng/ml as surrogate of protection.  An adequate AUC (greater than 0.80) was also observed for MenW and MenY with an estimated minimal threshold of 2.00 and 1.82 ng/ml, respectively.  When applying these thresholds, all (100 %) samples collected 1 month and 1 year after the (booster) meningococcal vaccination, that were defined as protective in the saliva test for MenC, MenW and MenY, corresponded with concomitant serum rSBA titer greater than or equal to 128 for the respective meningococcal serogroups.  The authors concluded that the saliva test offered an alternative screening tool to monitor protective vaccine responses up to 1 year after meningococcal vaccination against MenC, MenW and MenY.  These researchers stated that future, large, longitudinal vaccination studies evaluating also clinical protection against IMD or carriage acquisition are needed to validate the currently proposed threshold in saliva.

The authors stated that a drawback of this study was that only samples of children aged 10 to 15 years were used here to identify the salivary thresholds.  Thus, these salivary thresholds as surrogate of protection have to be validated in other large meningococcal vaccine trials, preferably studies that include participants with a wide age range.  furthermore, samples were collected only up to 1 year after vaccination.  Whether saliva samples could be used as a surrogate of protection in the long-term after vaccination has to be examined as well.

Table: CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":
CPT codes covered if selection criteria are met:
Meningococcal group B vaccine (Trumenba or Bexsero) [for individuals 10 years of age or older]:
90619	Meningococcal conjugate vaccine, serogroups A, C, W, Y, quadrivalent, tetanus toxoid carrier (MenACWY-TT), for intramuscular use
90620	Meningococcal recombinant protein and outer membrane vesicle vaccine, serogroup B, 2 dose schedule, for intramuscular use
90621	Meningococcal recombinant lipoprotein vaccine, serogroup B, 3 dose schedule, for intramuscular use
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
90733	Meningococcal polysaccharide vaccine, serogroups A, C, Y, W-135, quadrivalent (MPSV4), for subcutaneous use
90734	Meningococcal conjugate vaccine, serogroups A, C, Y and W-135, quadrivalent (MenACWY), for intramuscular use
Other CPT codes related to the CPB:
90471	Immunization administration (includes percutaneous, intradermal, subcutaneous, or intramuscular injections); 1 vaccine (single or combination vacctine/toxoid)
Other HCPCS codes related to the CPB:
J0596	Injection, c1 esterase inhibitor (recombinant), ruconest, 10 units
J0597	Injection, C-1 esterase inhibitor (human), berinert, 10 units
J0598	Injection, C1 esterase inhibitor (human) cinryze, 10 units
J1300	Injection, eculizumab, 10 mg
ICD-10 codes covered if selection criteria are met:
B20	Human immunodeficiency virus [HIV] disease
D57.00 - D57.819	Sickle-cell disorders
D84.1	Defects in the complement system
D89.89	Other specified disorders involving the immune mechanism, not elsewhere classified
Q89.01	Asplenia (congenital)
Z02.1	Encounter for pre-employment examination
Z02.3	Encounter for examination for recruitment to armed forces
Z02.89	Encounter for other administrative examinations
Z20.89	Contact with and (suspected) exposure to other communicable diseases
Z20.811	Contact with and (suspected) exposure to meningococcus
Z21	Asymptomatic human immunodeficiency virus [HIV] infection status
Z23	Encounter for immunization
Z59.3	Problems related to living in residential institution
Z65.8	Other specified problems related to psychosocial circumstances [military deployment status]
Z79.81	Acquired absence of spleen
Z90.81	Acquired absence of spleen
Z94.0	Kidney transplant status
Z94.1	Heart transplant status
Z94.2	Lung transplant status
Z94.3	Heart and lungs transplant status
Z94.4	Liver transplant status
Z94.82	Intestine transplant status
Z94.83	Pancreas transplant status
Saliva testing of antibody levels:
CPT codes not covered for indications listed in the CPB:
Saliva testing of antibody levels against meningococcal serogroups - no specific code:
ICD-10 codes not covered for indications listed in the CPB:
Z01.84	Encounter for antibody response examination [monitoring meningococcal vaccine responses]

The above policy is based on the following references: