Meningococcal Vaccine
Ira Shah
Meningococcal Vaccine - Introduction
Neisseria meningitidis is a leading cause of bacterial meningitis and other invasive bacterial infections worldwide. The role of the meningococcus as a cause of bacterial meningitis has become more pronounced in recent years with the declines in meningitis caused by Haemophilus influenzae type b and Streptococcus pneumoniae because of the introduction of new conjugate vaccines. The data available on the background incidence of Meningococcal disease in India are suggestive of low incidence of meningococcal disease.

N. meningitidis is a gram-negative diplococcus that is a strict human pathogen. It most commonly causes asymptomatic nasopharyngeal carriage but on occasion causes invasive disease. Clinical syndromes caused by N. meningitis include meningitis with or without meningococcemia, bacteremia, fulminant meningococcemia, pneumonia, and septic arthritis. The case fatality is around 12% but varies widely by clinical presentation. The biochemical composition of the polysaccharide capsule determines the serogroup of the strain. Although there are 13 different polysaccharide types, only 5, A, B, C, W-135, and Y are common causes of invasive disease. However Group A Meningococcus is the cause of all the major Indian epidemics.

Polysaccharide Vaccines: A meningococcal polysaccharide (MPS) vaccine, containing antigens of serogroups A, C, Y, and W135, (MPSV4) has been used since past 20 years. This vaccine protects against the serogroups that cause approximately two-thirds of meningococcal disease that occurs in people 18 to 23 years of age. Because group B polysaccharide is poorly immunogenic in humans, group B vaccines cannot be based on capsular polysaccharide. All four components of MPSV4 have been shown to be immunogenic in adults and older children. Serogroup A polysaccharide has some immunogenicity as early as 3 months of age, albeit not as much as in older children and adults, and serogroup C polysaccharide is poorly immunogenic in children under 2 years old. There are limited data on the duration of protection of MPSV4. Serum antibody levels decline significantly in infants and children under 5 years old but in healthy adults antibodies can still be detected after 10 years. However clinical protection wanes over time in both children and adults. Despite the utility of the MPSV4 in selected populations, there are major limitations that have restricted its widespread use, including lack of immunogenicity in infants, lack of immunologic memory and booster response, and relatively short duration of protection. Meningococcal polysaccharide vaccines have been shown to induce immunologic hyporesponsiveness. In this phenomenon, the antibody response in persons previously immunized with the meningococcal polysaccharide vaccine is less than that in persons receiving a first dose. Adverse reactions such as injection site pain and erythema, are common but usually mild. Transient fever can also occur in up to 5% of vaccinees. Severe adverse reactions are rare.

Meningococcal conjugate vaccines: Meningococcal conjugate vaccines, in which meningococcal polysaccharide is covalently linked to a carrier protein, are typically T-cell dependent, which confers major immunologic improvements over polysaccharide vaccines. One of the major advantages is immunogenicity in infants, which protects the age group with the highest incidence. Other advantages include induction of immunologic memory, a booster response, and the ability to overcome the immune hyporesponsiveness that is induced by the polysaccharide vaccine. Serogroup C meningococcal conjugate vaccines also reduce carriage of N. meningitidis in the nasopharynx, which leads to a decrease in transmission to unvaccinated persons.

Meninogoccal C conjugate vaccine (Men C): It has been routinely used in UK where infection due to serotype Y is minimum and maximum invasive disease occurs due to serotype C. A schedule of doses at 2, 3, and 4 months of age was introduced into the routine infant immunization schedule and, in addition, there was a catch-up campaign among children under 18 years old. In the 2 years after introduction of infant meningococcal conjugate vaccine, the incidence of serogroup C meningococcal disease declined by 87% in vaccinated people. There has been an approximately two-thirds drop in nasopharyngeal carriage of serogroup C N. meningitidis among 15- to 17-year-olds, as well a similar reduction in serogroup C meningococcal incidence among the unvaccinated population of all ages. Due to herd immunity. However, there clinical protection in infants immunized at 2, 3, and 4 months of age more than 1 year after immunization was not present despite evidence for continued protection in all other age groups that were targeted for immunization. Thus role of immunologic memory seems doubtful.

Quadrivalent meningococcal conjugate vaccines: In January 2005, a quadrivalent meningococcal conjugate vaccine (MCV4) was licensed by the U.S. Food and Drug Administration (FDA) for 11 to 55 year olds. A single dose of MCV4 contains 4 mcg each of the A, C, Y, and W-135 polysaccharides conjugated to 48 mcg of diphtheria toxoid. During prelicensure clinical trials antibody levels post vaccination to MCV4 were at least as high among adolescents and adults as responses to MPSV4. In 2011,
ACIP recommended a two-dose series of this vaccine
for use in children aged 9-23 months. Interference with PCV13 immune responses was noted when MCV-4 and PCV13
were administered simultaneously in patients with
asplenia. Hence, it is now recommended that at least one
month interval should be kept between PCV13 and
MenACWY-D, and PCV13 should be administered first.

Monovalent meningococcal A conjugate vaccine (Men A): First monovalent Meningococcal A conjugate vaccine was launched in Burkina Faso in Africa on 6th Dec 2010. The vaccine is recommended for children aged 1 year, adolescents and adults up to 29 years of age, for the prevention of invasive disease caused by Neisseria meningitides Group A. A single dose. of 0.5 ml should be administered by deep intramuscular injection. Six months after the successful introduction of MenAfriVac, the meningococcal A conjugate vaccine; Burkina Faso, Mali, and Niger report the lowest number of confirmed meningitis A cases ever recorded during an epidemic season.

The IAP recommends the use of Meningococcal vaccines only in certain high risk situations depicted below. The conjugate vaccines are preferred.
- During disease outbreaks, if caused by serogroups included in the vaccine
- Children with terminal complement component deficiencies.
- Children with functional/ anatomic asplenia/ hyposplenia
- Laboratory personnel and healthcare workers who are exposed routinely to Neisseria meningitides in solutions that may be aerosolized should be considered for vaccination.
- Travelers to Saudi Arabia for Haj (mandatory requirement)
- Travelers to the African meningitis belt particularly between December to June and especially if there is an ongoing epidemic.
- Students going for study abroad (mandatory in most universities in the USA)

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