Meningococcal vaccines important as rates rise

June 2005

Neisseria meningitidis has become a significant cause of meningitis and severe sepsis due to the decreasing rates of H. influenzae type b and S. pneumoniae following the introduction of their conjugated vaccines.

Meningococcus causes an estimated 2,500 cases of invasive disease each year in the United States. Invasive meningococcal disease is associated with an estimated 15% mortality rate and morbidity in survivors is substantial with approximately 20% having loss of limb or neurologic sequelae. Meningococcal disease usually occurs during the winter and early spring. The highest rates of meningococcal disease are among young children. However, rates have been increasing in adolescents and young adults.

Thirteen meningococcal serogroups have been identified. However, five serogroups A, B, C, Y, W-135, are responsible for epidemic and endemic disease worldwide. N. meningitidis colonizes the nasopharynx and is transmitted through direct contact with large droplet respiratory secretions. Despite the availability of highly active antibacterial agents against N. meningitidis, there has been little impact on decreasing the morbidity and mortality to invasive meningococcal disease. This emphasizes the need for measures to prevent acquisition of meningococcus through vaccination.

A meningococcal polysaccharide vaccine containing serogroups A, C, Y, and W-135 has been available in the United States for a number of years. Meningococcal polysaccharide vaccine is similar to other polysaccharide vaccines, in that it is poorly immunogenic in infants and children less than 2 years of age and does not produce lasting immunity. Meningococcal polysaccharide vaccine produces a T-cell independent response and fails to induce a memory response. Repeated vaccination results in hyporesponsiveness to serogroups A and C, however, the clinical implication of this finding is unknown. Additionally meningococcal polysaccharide vaccine has had minimal effect on nasopharyngeal carriage of meningococcus and has not produced herd immunity. These details have limited the use of meningococcal polysaccharide vaccine to specific situations and highlighted the need for a better vaccine.

In January 2005, a new meningococcal polysaccharide diphtheria toxoid conjugate vaccine (Menactra, Sanofi Aventis) was approved by the FDA. This vaccine also contains meningococcal serogroups A, C, Y, and W-135. Polysaccharide-protein conjugate vaccines are known to produce improved immunogenicity and memory responses. Meningococcal conjugate vaccine was approved by demonstrating immunologic equivalence to the licensed meningococcal polysaccharide vaccine in several non-inferiority studies. The primary endpoint was the induction of serogroup-specific anti-capsular antibody that possessed bactericidal activity. Vaccine efficacy was inferred by the presences of immunologic response of a four-fold increase in serum bactericidal antibodies for each serogroup. Safety of the vaccine was also evaluated.

The studies in adolescents between the ages of 11 and 18 years showed a similar immunologic response for all four serogroups when comparing those receiving the meningococcal conjugate vaccine to those receiving the meningococcal polysaccharide vaccine. The results were also similar for adults aged 18 to 55 years. (See Table.) In both groups there was a trend toward better immune response of the meningococcal polysaccharide vaccine to serogroup Y. However, this was not statistically significantly.

Meningococcal conjugate vaccine has been administered to people previously vaccinated with either meningococcal conjugate vaccine or meningococcal polysaccharide vaccine to assess the response to revaccination. Those people primed with meningococcal conjugate vaccine achieved a higher immunologic response than those primed with meningococcal polysaccharide vaccine. However, routine revaccination is not recommended at this time.

Vaccine safety

The safety of meningococcal conjugate vaccine was assessed in six clinical trials. Local adverse reactions, pain at the injection site, and fever were more common with the meningococcal conjugate vaccine than the meningococcal polysaccharide vaccine. This is likely due to the amount of diphtheria toxoid contained in each vaccine. Serious adverse effects were similar between the meningococcal conjugate and meningococcal polysaccharide vaccines.

The recommendations for use of the meningococcal vaccines were just released by the CDC’s Advisory Committee on Immunization Practices (ACIP). Meningococcal conjugate vaccine is recommended for routine vaccination of young adolescents ages 11 and 12 years. This may be done at the routine preadolescent health care visit where immunization status should be assessed along with other preventive health services. Routine vaccination is also recommended for people at increased risk for meningococcal disease, such as college freshman living in dormitories, microbiologists who are routinely exposed to isolates of N. meningitidis, military recruits, people who travel to or reside in countries in which N. meningitidis is hyperendemic or epidemic, people who have terminal complement component deficiencies, and persons who have anatomic or functional asplenia. Meningococcal conjugate vaccine is preferred for persons between the ages of 11 and 55 years. However, the safety and efficacy of meningococcal conjugate vaccine has not been established for people ages 2 to 10 and older than 55 years. In these people, the meningococcal polysaccharide vaccine should be used.

The meningococcal conjugate vaccine is a key addition to the prevention of invasive meningococcal disease. However, several questions remain regarding its use, such as the duration of immune protection, the vaccine’s effectiveness in altering meningococcal transmission patterns and effects on herd immunity. Additional time and use of the vaccine will be necessary to answer these questions.

For more information:

• Centers for Disease Control and Prevention. Prevention and control of meningococcal disease recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 2005;54(No. RR-7):1-21.
• Danzig L. Meningococcal vaccines. Pediatr Infect Dis J. 2004;23:S285-S292.
• Pollard AJ. Global epidemiology of meningococcal disease and vaccine efficacy. Pediatr Infect Dis J. 2004;23:S274-S279.

• Marianne Billeter, PharmD, BCPS, Clinical Pharmacology Specialist, Infectious Diseases, Ochsner Clinic Foundation, New Orleans.