ndividually conjugated to diphtheria toxoid protein. N meningitidis A, C, Y and W-135 strains are cultured on Mueller Hinton agar (2) and grown in Watson Scherp (3) 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 medium (4) 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 serogroup-specific glycoconjugates, compose the final formulated vaccine. No preservative or adjuvant is added during manufacture. Each 0.5 mL dose may contain residual amounts of formaldehyde of less than 2.66 mcg (0.000532%), by calculation. 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 mcg each of meningococcal A, C, Y and W-135 polysaccharides conjugated to approximately 48 mcg of diphtheria toxoid protein carrier.
There is no latex in any component of the vial.
12.CLINICAL PHARMACOLOGY
12.1.Mechanism of Action
The presence of bactericidal anti-capsular meningococcal antibodies has been associated with protection from invasive meningococcal disease. (5) (6) Menactra vaccine induces the production of bactericidal antibodies specific to the capsular polysaccharides of serogroups A, C, Y and W-135.
13. NON-CLINICAL TOXICOLOGY
13.1.Carcinogenesis, Mutagenesis, Impairment of Fertility
Menactra vaccine has not been eva luated for carcinogenic or mutagenic potential, or for impairment of fertility.
14.CLINICAL STUDIES
14.1. Efficacy
The Serum Bactericidal Assay (SBA) used to test sera contained an exogenous complement source that was either human (SBA-H) or baby rabbit (SBA-BR). (7)
The response to vaccination following two doses of vaccine administered to children 9 and 12 months of age and following one dose of vaccine administered to children 2 through 10 years of age was eva luated by the proportion of subjects having an SBA-H antibody titer of 1:8 or greater, for each serogroup. In individuals 11 through 55 years of age, the response to vaccination with a single dose of vaccine was eva luated by the proportion of subjects with a 4-fold or greater increase in bactericidal antibody to each serogroup as measured by SBA-BR. For individuals 2 through 55 years of age, vaccine efficacy was inferred from the demonstration of immunologic equivalence to a US-licensed meningococcal polysaccharide vaccine, Menomune – A/C/Y/W-135 vaccine as assessed by Serum Bactericidal Assay (SBA).
14.2.Immunogenicity
Children 9 through 12 Months of Age
In a randomized, US, multi-center trial, children received Menactra vaccine at 9 months and 12 months of age. The first Menactra dose was administe
