Disease- and Population-Specific Immunizations

Meningococcal Disease Vaccine

The Neisseria meningitides bacteria cause invasive diseases in the form of meningitis and sepsis. The disease can strike rapidly and unexpectedly in healthy individuals. Although it can strike any age group, very young children and persons 16 to 23 years have the highest incidence. The bacteria have caused epidemics on the African continent. In the U.S., the disease tends to occur sporadically or in small outbreaks. The disease is deadly with a case-fatality rate of 10 to 15%. As many as 20% of survivors are often left with neurologic damage, limb loss, or hearing impairment. There are at least 13 strains of Neisseria meningitides, but the A, B, C, W, and Y serogroups account for the vast majority of invasive disease.1

Meningococcal Vaccines

The first meningococcal vaccines developed were polysaccharide vaccines.1 MPSV4 (Menomune®)
contains four purified bacterial polysaccharides and cover strains A, C, W, and Y. The use of the vaccine has been limited by its short duration of action.1

The next vaccines developed were the quadrivalent meningococcal conjugate vaccines. Men ACYW (Menactra® and Menveo®) are composed of capsular polysaccharide conjugated to a protein and cover meningococcal strains A, C, W, and Y. The Men ACYW vaccines are recommended for routine use in adolescents aged 11 or 12 years, with a booster dose at age 16 years.2   

Hib-MenCY-TT (MenHibrix®) offers protection against Y and C serotypes of Neisseria Meningities, as well as Haemophilus influenza. It may be given to children at increased risk of meningococcal disease starting at six weeks and up to 18 months of age. If given, the vaccine counts as an HIB dose.

In 2014 and 2015, two vaccines offering protection against the B serotype of meningococcus were licensed. MenB-FHbp (Trumenba®) and MenB-4C (Bexsero®) are composed of novel protein or lipoprotein antigens.3

Meningococcal B Vaccine: Frequently Asked Questions

In June 2015, the U. S. Advisory Committee on Immunizations Practices (ACIP) provided a category B recommendation for both Men B vaccines, making the vaccine appropriate for individual clinical decision-making:

A serogroup B meningococcal (Men B) 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 Men B vaccination is 16 through 18 years of age.3,4

This is not a category A or “routine” recommendation, so many health care providers and patients have questions about the vaccine. Below is a list of frequently asked questions that may assist with decision-making:

Should low risk patients aged 16 to 23 be advised to get one of the new Men B vaccines?

There is no clear answer to that question. Persons aged 16 to 23 are at an increased risk of contracting meningococcal infections. However, the incidence of Men B disease is low and seems to be getting lower. There is limited information about the clinical efficacy and safety of the vaccines. This is one of the reasons the ACIP gave this recommendation a B rather than an A rating.3,4

Why did the ACIP make a category B recommendation for Men B vaccination of persons 16 to 23 years of age instead of a category A recommendation like most vaccines?

Category B recommendations call for personalized clinical decision-making between clinician and patient.5 In a report to the ACIP, the Meningococcal Work Group noted, “key data on Men B vaccines are not yet available."4

What about patients that are at greater risk of meningococcal B infections?

The ACIP recommends routinely administering Men B vaccines among certain individuals 10 years or older who are at increased risk for serogroup B meningococcal disease. This includes those individuals with complement component deficiencies; anatomic or functional asplenia; microbiologists routinely exposed to isolates of Neisseria meningitides; and those at increased risk because of a serogroup B meningococcal disease outbreak. This is a category A recommendation.6

How common are meningococcal B infections?

All serotypes of meningococcal disease are rare, and the incidence seems to be decreasing. The incidence of all meningococcal B serotype infections in the United States is estimated to be about 200 cases per year among persons of all ages. The incidence of Men B is highest in children age five or younger, with an estimated 75 to 100 cases per year. However, the Men B vaccines are not licensed in the U.S. for this age group. In the U.S., the estimated average number of cases in 11 to 24 year olds is 54 to 67 per year. The majority of cases (98%) are sporadic, but up to two percent can occur in outbreaks.1 Since 2009, seven outbreaks of serogroup B meningococcal disease have occurred on college campuses. Cases have occurred in settings outside of college campuses, as well.4  

What is the difference between the meningococcal vaccines we have been using and the new Men B vaccines?

The polysaccharide in the B strains of meningococcus is similar to a polysaccharide found in humans making Men B vaccines more challenging to develop.7 The development of these vaccines required sequencing of the bacterial genome to find proteins unique to the Neisseria bacterial wall that could be used as antigens to stimulate immunity in humans. Using this innovative process, two Men B vaccines, MenB-FHbP (Trumenba®) and MenB-4C (Bexsero®), were developed. Each vaccine is composed of novel protein or lipoprotein antigens. Therefore, the vaccines are not interchangeable.   

How effective are the Men B vaccines in preventing meningococcal B infections?

Clinical trials of vaccine effectiveness are not practical or possible because the incidence of disease is low. Instead, vaccine efficacy was based on "complement mediated antibody killing" detected in serum of individuals who received the vaccines, a surrogate measure of protection.3,4,8,9 In separate studies, vaccines were given to different adolescent populations ranging in age from 11 to 65 years. Eighty-four percent of subjects who received three doses of MenB-FHpb, and 63 to 94% who received two doses of MenB4C were considered immune, based on immunogenicity studies to four strains of meningococcus B that occur in the U.S.3,4 Other strains will be tested in the future. 

Long-term studies have not yet been reported on either vaccine. In both vaccines, there was modest decline in antibodies with time (6 to 48 months). The clinical significance of this immunologic data is unclear. It is possible that the vaccines could continue to protect against infection even in persons with low antibody titers. 

Will immunizing populations decrease carriage of the meningococcal B bacteria?

So far, limited studies have not shown a decrease of asymptomatic carriage in immunized populations.  More studies are planned.4

What are the risks and side effect of the Men B vaccines?

Both vaccines have a tendency to cause minor, self-limiting reactions, such as pain at the injection site, fever, headache, fatigue, myalgia, and arthralgia. The incidence of these reactions does not seem to be higher than similar reactions with other vaccines.8,9

There is a theoretic risk that Men B vaccines could cause autoimmune disease. Both vaccines contain factor H binding protein, which in animal models was noted to be cross-reactive with human factor H. It is not known if auto-antibodies are generated in humans and the clinical significance of any antibodies is unknown.3 Two non-fatal anaphylaxis cases have been associated with the use the Men B vaccine. One case for each vaccines.

FDA approval for the Men B vaccines was granted via an accelerated process, based on 3,000 to 4,000 subjects. Since FDA approval was granted, additional data on more subjects was collected when the vaccines were used during outbreaks on college campuses. 

For the MenB-FHbp vaccine, there were reports of 13 cases of autoimmune conditions in the 4,576 persons who received the MenB-FHbp vaccine and none in the 1,028 controls.8 On closer examination, the reported conditions were felt to predate the vaccine, have other explanations for causation, or did not have a higher rate than expected in the population. Additional information was presented in June 2015, to the ACIP including seven creditable, serious adverse events (pyrexia, vomiting, vertigo, chills, headache, anaphylaxis, and neutropenia in 4 out of 9,808 persons who received at least one dose of this vaccine. All adverse effects resolved without long-term consequences.3,4

What is the price of the Men B vaccines?

MenB-FHbp is a three-dose series with a Centers for Disease Control and Prevention (CDC) private sector price of $115.75 per does or $347 for the series. MenB-4C is a two-dose series with a CDC price of $160.75 per doses or $322 for the series.10 Assuming a birth cohort of four million, the cost of vaccinating all 16 to 23-year-olds would be more than one billion dollars. The ACIP estimates the cost per quality-adjusted life year to be in excess of four million dollars.3,4

Are the vaccines covered by insurance?

Under provisions of the Affordable Care Act, the vaccine should be covered by commercial insurance. The Vaccines for Children program covers qualified children under the age of 18.

When will there be more information about the Men B vaccines?

In the United Kingdom, Men B vaccines are approved for children eight weeks to two years. As in the U.S., this age group has higher incidence of disease than the adolescent/young adult age group.11 As a result of experience with the vaccines in the U.S. and other countries, more information will emerge in the next few years. Until then, physicians and patients need to understand the potential risks, as well as benefits of these new vaccines.

Where can I get more information?

More information is available at the CDC/ACIP website(www.cdc.gov).


References

1. Hambrosky J, Kroger A, Wolfe S, eds. Centers for Disease Control and Prevention. Epidemiology and Prevention of Vaccine Preventable Diseases. 13th ed. Washington, D.C. Public Health Foundation; 2015.

2. Cohn A, MacNeil JR, Clark TA, et al. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices. MMWR. 2013;62(RR02):1-22.

3. MacNeil J, Rubin L, Temitope F, Ortega-Sanchez I. Use of serogroup B meningococcal vaccines in adolescents and young adults: recommendations of the Advisory Committee on Immunization Practices. MMWR. 2015;64(41):1171-1176.

4. MacNeil J. Considerations for use of serogroup B meningococcal (MenB) vaccines in adolescents. Presented to the Advisory Committee on Immunization Practices. June 24, 2015. http://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2015-06/mening-03-macneil.pdf(www.cdc.gov). Accessed October 10, 2015.

5. Centers for Disease Control and Prevention. Evidence-based recommendations—GRADE. http://www.cdc.gov/vaccines/acip/recs/grade/about-grade.html(www.cdc.gov). Accessed October 10, 2015.

6. Folaranmi T, Rubin L, Martin S, Patel M, MacNeil J. Use of serogroup B meningococcal vaccines in persons aged ≥10 years at increased risk for serogroup B meningococcal disease: recommendations of the Advisory Committee on Immunization Practices. MMWR. 2015;64(22);608-612.

7. Leca M, Bornetb C, Montanac M, Curti C, Vanelled P. Meningococcal vaccines: current state and future outlook. Pathologie Biologie. 2015;63:144–151.

 8. U.S. Food and Drug Administration. Summary basis for action: Trunemba. http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm421020.htm(www.fda.gov)Accessed October 10, 2015.

 9. U.S. Food and Drug Administration. Summary basis for action: Bexsero. http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm431374.htm(www.fda.gov)Accessed October 10, 2015.

 10. Centers for Disease Control and Prevention. CDC vaccine price list. http://www.cdc.gov/vaccines/programs/vfc/awardees/vaccine-management/price-list/index.html(www.cdc.gov)Accessed November 15, 2015.

 11. National Health Service England. Patient Group Direction. Administration of Bexsero® suspension for injection (meningococcal group B vaccine (rDNA, component, adsorbed)). Individuals from 8 weeks of age eligible for the national routine immunisation programme and prevention of secondary cases of Men B disease. https://www.england.nhs.uk/south/wp-content/uploads/sites/6/2015/07/phe-menb-pgd-1.pdf(www.england.nhs.uk)Accessed November 15, 2015.