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Meningococcal(Groups A, C,Y and W-135)Polysaccharide
2015-07-27 10:24:56 来源: 作者: 【 】 浏览:371次 评论:0
Meningococcal (Groups A, C, Y and W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine
Menactra®

 

 

AHFS Category: 80:12

MCV4

Rx only

FOR INTRAMUSCULAR INJECTION

 

DESCRIPTION

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 agar (1) and grown in Watson Scherp(2) 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 (3) 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 2.66mcg (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.

 

CLINICAL PHARMACOLOGY

 

Background

The meningococcus bacterium, N meningitidis, causes both endemic and epidemic disease, principally meningitis and meningococcemia. At least 13 meningococcal serogroups have been identified based on antigenic differences in their capsular polysaccharides. Five serogroups (A, B, C, Y and W-135) are responsible for nearly all cases of meningococcal disease worldwide. (4) (5) Early clinical manifestations of meningococcal disease are often difficult to distinguish from other, more common but less serious illnesses. (6) Onset and progression of disease can be rapid; in most cases (60%), infected individuals are symptomatic for less than 24 hours before seeking medical care. Even with administration of appropriate antimicrobials and other adjunctive therapies, the case-fatality rate has remained at approximately 10%. (6) (7) (8) (9) In cases of fulminant septicemia, the case fatality rate may reach 40%. (6) Approximately 11-19% (5) of meningococcal disease survivors have sequelae such as hearing loss and neurologic disability, or loss of skin, digits or limbs as a result of ischemia.

 

Mechanism of Action

The presence of bactericidal anti-capsular meningococcal antibodies has been associated with protection from invasive meningococcal disease. (10) (11) Menactra vaccine induces the production of bactericidal antibodies specific to the capsular polysaccharides of serogroups A, C, Y and W-135.

 

Clinical Studies

Vaccine efficacy was inferred from the demonstration of immunologic equivalence to a US-licensed meningococcal polysaccharide vaccine, Menomune®–A/C/Y/W-135, Meningococcal Polysaccharide Vaccine, Groups A, C, Y and W-135 Combined as assessed by Serum Bactericidal Assay (SBA). The SBA used to test sera contained an exogenous complement source that was either human (SBA-H) or, when correlated to SBA-H, baby rabbit (SBA-BR). (12)

The response to vaccination in children 2–10 years old was eva luated by the proportion of subjects having an SBA-H antibody titer of 1:8 or greater, for each serogroup. In adolescents and adults, the response to vaccination 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.

Immunogenicity was eva luated in three comparative, randomized, US, multi-center, active controlled clinical trials that enrolled children (2–10 years old), adolescents (11–18 years old), and adults (18–55 years old). Participants received a dose of Menactra vaccine (N=2526) or Menomune–A/C/Y/W-135 vaccine (N=2317). For all age groups studied, sera were obtained before and approximately 28 days after vaccination. (Blinding procedures for safety assessments are described in ADVERSE REACTIONS section.)

In each of the trials, there were no substantive differences in demographic characteristics between the vaccine groups, between immunogenicity subsets or the overall study population. In the study of children 2–10 years old, the median age of participants was 3 years old; 95% completed the study. In the adolescent trial, the median age for both groups was 14 years; 99% completed the study. In the adult trial, the median age for both groups was 24 years; 94% completed the study.

 

Immunogenicity in Children

Of 1408 enrolled children 2–10 years old, immune responses eva luated in a subset of Menactra vaccine participants (2–3 years old, n=52; 4–10 years old, n=84) and Menomune–A/C/Y/W-135 vaccine participants (2–3 years old, n=53; 4–10 years old, n=84) were comparable for all four serogroups (Table 1 and Table 2).

Table 1: Comparison of Bactericidal Antibody Responses * to Menactra vaccine and Menomune–A/C/Y/W-135 vaccine 28 Days After Vaccination for a Subset of Participants Aged 2–3 Years
    Menactra vaccine
N=48-52
Menomune–A/C/Y/W-135 vaccine
N
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