Meningococcal Meningitis Strains

N. meningitidis strains are grouped on the basis of their capsular polysaccharides. There are at least 13 serogroups, some of which are subdivided according to the presence of outer membrane protein and lipopolysaccharide antigens.

Meningococcal capsular polysaccharides provide the basis for grouping the organism. Twelve serogroups have been identified (A, B, C, H, I, K, L, X, Y, Z, 29E, and W135). The most important serogroups associated with disease in humans are A, B, C, Y, and W135. The chemical composition of these capsular polysaccharides is known. The prominent outer membrane proteins of N. meningitidis have been designated class 1 through class 5. The class 2 and 3 proteins function as porins and are analogous to gonococcal Por. The class 4 and 5 proteins are analogous to gonococcal Rmp and Opa, respectively. Serogroup B and C meningococci have been further subdivided on the basis of serotype determinants located on the class 2 and 3 proteins. A handful of serotypes are associated with most cases of meningococcal disease, whereas other serotypes within the same serogroup rarely cause disease. All known group A strains have the same protein serotype antigens in the outer membrane. Another serotyping system exists based on the antigenic diversity of meningococcal LOS (lipooligopolysaccharide).

  

Infection with N. meningitidiscan present in two ways. Either as meningococcemia, characterized by skin lesions, or as acute bacterial meningitis.

 Five predominant strains or serogroups of N. meningitidis account for most cases of meningococcal disease. These are A, B, C, Y, and W-135. The currently available capsular polysaccharide vaccines are available for four of the five strains (A, C, Y, and W-135) No vaccine is available for widespread vaccination against serogroup B.

The group B capsular polysaccharide is a homopolymer of sialic acid which is not immunogenic in humans. A group B meningococcal vaccine consisting of outer membrane protein antigens has been developed, but is not licensed in the United States. Polysaccharide vaccines are ineffective in young children. In children under 1 year old, antibody levels decline rapidly after immunization.The duration of protection is also limited in children vaccinated at 1 to 4 years of age.  Routine vaccination is not currently recommended due to the risk of infection as being classified as low.

  

There are two vaccines against N. meningitidis available in the U.S.

Meningococcal polysaccharide vaccine (MPSV4 or Menomune®) has been approved by the Food and Drug Administration (FDA) and available since 1981.

Meningococcal conjugate vaccine (MCV4 or MenactraT) was licensed in 2005. Both vaccines can prevent 4 types of meningococcal disease, including 2 of the 3 types most common in the U.S. (serogroup C, Y, and W-135) and a type that causes epidemics in Africa (serogroup A).

Meningococcal vaccines cannot prevent all types of the disease.

 MCV4 is recommended for all children at their routine preadolescent visit (11 to 12 years of age). MCV4 is the preferred vaccine for people 11 to 55 years of age in these risk groups, but MPSV4 can be used if MCV4 is not available. MPSV4 should be used for children 2 to 10 years old and adults over 55, who are at risk.

  

MPSV4: Meningococcal Polysaccharide Vaccine, Groups A, C, Y and W-135 Combined

Menomune® – A/C/Y/W-135

 Menomune® – A/C/Y/W-135, Meningococcal Polysaccharide Vaccine, Groups A, C, Y and W-135 Combined, for subcutaneous use, is a freeze-dried preparation of the group-specific polysaccharide antigens from Neisseria meningitidis, Group A, Group C, Group Y and Group W-135. N meningitidis are cultivated with Mueller Hinton agar1 and Watson Scherp2 media. The purified polysaccharide is extracted from the Neisseria meningitidis cells and separated from the media by procedures which include centrifugation, detergent precipitation, alcohol precipitation, solvent or organic extraction and diafiltration. No preservative is added during manufacture.

The 0.78 mL vial of diluent contains sterile, preservative-free, pyrogen-free distilled water and is used for reconstitution of product supplied in 1 mL vials. The 6 mL vial of diluent contains sterile, pyrogen-free distilled water to which thimerosal (mercury derivative) 1:10,000 is added as a preservative. The 6 mL vial is for reconstitution of product supplied in 10 mL vials.

After reconstitution with diluent as indicated on the label, the 0.5 mL dose is formulated to contain 50 μg of “isolated product” from each of Groups A, C, Y and W-135 in an isotonic sodium chloride solution.

 

 MCV4: Meningococcal (Groups A, C, Y and W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine Menactra®

 

Menactra®, Meningococcal (Groups A, C, Y and W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine, is a sterile, intramuscularly administered vaccine that contains Neisseria meningitidis serogroup A, C, Y and W-135 capsular polysaccharide antigens individually conjugated to diphtheria toxoid protein. N meningitidis A, C, Y and W-135 strains are cultured on Mueller Hinton agar1 and grown in Watson Scherp2 media. The polysaccharides are extracted from the N meningitidis cells and purified by centrifugation, detergent precipitation, alcohol precipitation, solvent extraction and diafiltration. To prepare the polysaccharides for conjugation, they are depolymerized, derivatized, and purified by diafiltration. Corynebacterium diphtheriae cultures are grown in a modified Mueller and Miller medium3 and detoxified with formaldehyde. The diphtheria toxoid protein is purified by ammonium sulfate fractionation and diafiltration. The derivatized polysaccharides are covalently linked to diphtheria toxoid and purified by serial diafiltration. The four meningococcal components, present as individual serogroupspecific glycoconjugates, compose the final formulated vaccine. No preservative or adjuvant is added during manufacture.

Potency of Menactra vaccine is determined by quantifying the amount of each polysaccharide antigen that is conjugated to diphtheria toxoid protein and the amount of unconjugated polysaccharide present.

Menactra vaccine is manufactured as a sterile, clear to slightly turbid liquid. Each 0.5 mL dose of vaccine is formulated in sodium phosphate buffered isotonic sodium chloride solution to contain 4 μg each of meningococcal A, C, Y, and W-135 polysaccharides conjugated to approximately 48 μg of diphtheria toxoid protein carrier.

 

 Advantages of Meningococcal Conjugate Vaccines (ACIP meeting May 27, 2005 / 54(RR07); 1-21)

Bacterial polysaccharides, including those comprising the capsule of N. meningitdis, are T-cell–independent antigens. T-cell–independent antigens do not elicit a memory response; they stimulate mature B-lymphocytes but not T-lymphocytes, thus inducing a response that is neither long-lasting nor characterized by an anamnestic response after subsequent challenge with the same polysaccharide antigen (72). Thus, meningococcal polysaccharide vaccines have inherent limitations. The serogroup C polysaccharide is poorly immunogenic among children aged <2 years (73–75). The A polysaccharide induces antibody response in infants, but vaccine efficacy declines rapidly (64). Meningococcal polysaccharide vaccines do not confer long-lasting immunity (61,64); they also do not cause a sustainable reduction of nasopharyngeal carriage of N. meningitdis (76,77) and therefore do not substantially interrupt transmission to elicit herd immunity. Finally, multiple doses of serogroup A and C polysaccharide vaccine might cause immunologic hyporesponsiveness to the group A (56,57) and C (58,59) polysaccharide, although clinical implications of this phenomenon are unknown.

Conjugation (i.e., covalent coupling) of polysaccharide to a protein carrier that contains T-cell epitopes changes the nature of immune response to polysaccharide from T-cell–independent to T-cell–dependent, leading to a substantial primary response among infants and a strong anamnestic response at re-exposure (78). Both conjugate Hib and conjugate S. pneumoniae vaccines (introduced for mass infant immunization in the United States in 1990 and 2000, respectively) have reduced incidence of disease caused by vaccine-preventable serotypes (1,79). In addition, both vaccines reduce asymptomatic carriage of respective bacteria (80–82), thus protecting unvaccinated persons through a herd immunity effect (1).

 

What was said in 1990 in regards to polysaccharide vaccine:

 Notice to Readers Availability of Meningococcal Vaccine in Single-Dose Vials for Travelers and High-Risk Persons (MMWR Weekly October 26, 1990 / 39(42);763)

The Food and Drug Administration has approved a single-dose vial of quadrivalent polysaccharide vaccine against Neisseria meningitidis serogroups A, C, Y, and W135. The single-dose vial replaces the previously available 10-dose vial, which, once reconstituted, has a 5-day shelf life. This limitation is obviated by the single-dose vial and should facilitate administration to persons at high risk.

Immunization is recommended for persons with anatomic or functional asplenia and deficiencies of the terminal components of the complement system. Additionally, travelers to areas with hyperendemic or epidemic meningococcal disease should be immunized (1). Updated travel advisories can be obtained from travelers’ clinics, county and state health departments, and CDC.

The vaccine is not recommended for routine use in the United States for three reasons: 1) meningococcal disease is infrequent (approximately 3000 cases per year); 2) no vaccine exists for serogroup B, which accounts for about 50% of cases in the United States; and 3) vaccine is not efficacious against group C disease in children less than 2 years of age (2). This age group accounts for 28% of the group C cases in the United States (CDC, unpublished data).

In adults, the protective efficacy of the vaccine is 85%-95% for disease caused by serogroups A or C (3, 4). Efficacy data are not available for serogroups Y and W135, but the vaccine is immunogenic for both of these serogroups (5-7). Side effects of the vaccine are mild and infrequent, consisting primarily of erythema and induration at the site of injection and low-grade fever. Protective immunity is achieved 10-14 days after vaccination.

Meningococcal lipopolysaccharides: virulence factor and potential vaccine component.  (Microbiol Rev. 1993 March; 57(1): 34–49. PMCID: PMC372900)

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