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.⁶Onset 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 (polysaccharide diphtheria toxoid conjugate vaccine) 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 evaluated 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 evaluated 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 evaluated 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 (polysaccharide diphtheria toxoid conjugate vaccine) 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 evaluated in a subset of Menactra (polysaccharide diphtheria toxoid conjugate vaccine) 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 (polysaccharide diphtheria toxoid conjugate vaccine) vaccine and Menomune-A/C/Y/W-135 vaccine 28 Days After Vaccination for a Subset of Participants Aged 2-3 Years

Table 2: Comparison of Bactericidal Antibody Responses* to Menactra (polysaccharide diphtheria toxoid conjugate vaccine) vaccine and Menomune-A/C/Y/W-135 vaccine 28 Days After Vaccination for a subset of Participants Aged 4-10 Years

In the subset of participants 2-3 years of age with undetectable pre-vaccination titers (ie, < 4 at Day 0), seroconversion rates (defined as ≥ 8 at Day 28) were similar between the Menactra (polysaccharide diphtheria toxoid conjugate vaccine) vaccine and Menomune-A/C/Y/W-135 vaccine recipients. Menactra (polysaccharide diphtheria toxoid conjugate vaccine) vaccine participants achieved seroconversion rates of: 57%, Serogroup A (n=12/21); 62%, Serogroup C (n=29/47); 84%, serogroup Y (n=26/31); 53%, serogroup W-135 (n=20/38). The seroconversion rates for Menomune-A/C/Y/W-135 vaccine recipients were 55%, Serogroup A (n=16/29); 30%, Serogroup C (n=13/43); 57%, serogroup Y (n=17/30); 26%, serogroup W-135 (n=11/43).

In the subset of participants 4-10 years of age, percentages of participants that achieved seroconversion were similar between the Menactra (polysaccharide diphtheria toxoid conjugate vaccine) vaccine and Menomune-A/C/Y/W-135 vaccine recipients. Menactra (polysaccharide diphtheria toxoid conjugate vaccine) vaccine participants achieved seroconversion rates of: 69%, Serogroup A (n=11/16); 81%, Serogroup C (n=50/62); 98%, serogroup Y (n=45/46); 69%, serogroup W-135 (n=27/39). The seroconversion rates for Menomune-A/C/Y/W-135 vaccine recipients were 48%, Serogroup A (n=10/21); 38%, Serogroup C (n=19/50); 84%, serogroup Y (n=38/45); 68%, serogroup W-135 (n=26/38).

Immunogenicity in Adolescents

Results from the comparative clinical trial conducted in 881 adolescents aged 11-18 years showed that the immune responses to Menactra (polysaccharide diphtheria toxoid conjugate vaccine) vaccine and Menomune-A/C/Y/W-135 vaccine were similar for all four serogroups (Table 3).

Table 3: Comparison of Bactericidal Antibody Responses* to Menactra (polysaccharide diphtheria toxoid conjugate vaccine) Vaccine and Menomune-A/C/Y/W-135 Vaccine 28 Days after Vaccination for Participants Aged 11-18 Years

In participants with undetectable pre-vaccination titers (ie, less than 8 at Day 0), seroconversion rates (defined as a ≥ 4-fold rise in Day 28 SBA titers) were similar between the Menactra (polysaccharide diphtheria toxoid conjugate vaccine) vaccine and Menomune-A/C/Y/W-135 vaccine recipients. Menactra (polysaccharide diphtheria toxoid conjugate vaccine) vaccine participants achieved seroconversion rates of: 100%, Serogroup A (n=81/81); 99%, Serogroup C (n=153/155); 98%, Serogroup Y (n=60/61); 99%, Serogroup W-135 (n=161/164). The seroconversion rates for Menomune-A/C/Y/W-135 vaccine recipients were 100%, Serogroup A (n=93/93); 99%, Serogroup C (n=151/152); 100%, Serogroup Y (n=47/47); 99%, Serogroup W-135 (n=138/139).

Immunogenicity in Adults

Results from the comparative clinical trial conducted in 2554 adults aged 18-55 years showed that the immune responses to Menactra (polysaccharide diphtheria toxoid conjugate vaccine) vaccine and Menomune-A/C/Y/W-135 vaccine were similar for all four serogroups (Table 4).

Table 4: Comparison of Bactericidal Antibody Responses* to Menactra (polysaccharide diphtheria toxoid conjugate vaccine) Vaccine and Menomune-A/C/Y/W-135 Vaccine 28 Days After Vaccination for Participants Aged 18-55 Years

In participants with undetectable pre-vaccination titers (ie, less than 8 at Day 0), seroconversion rates (defined as a ≥ 4-fold rise in Day 28 SBA titers) were similar between the Menactra (polysaccharide diphtheria toxoid conjugate vaccine) vaccine and Menomune-A/C/Y/W-135 vaccine recipients. Menactra (polysaccharide diphtheria toxoid conjugate vaccine) vaccine participants achieved seroconversion rates of: 100%, Serogroup A (n=156/156); 99%, Serogroup C (n=343/345); 91%, Serogroup Y (n=253/279); 97%, Serogroup W-135 (n=360/373). The seroconversion rates for Menomune-A/C/Y/W-135 vaccine recipients were 99%, Serogroup A (n=143/144); 98%, Serogroup C (n=297/304); 97%, Serogroup Y (n=22½28); 99%, Serogroup W-135 (n=325/328).

Concomitant Vaccine Administration

Tetanus and Diphtheria

The concomitant use of Menactra (polysaccharide diphtheria toxoid conjugate vaccine) vaccine and Tetanus and Diphtheria Toxoids Adsorbed, For Adult Use (Td, manufactured by Sanofi Pasteur Inc., Swiftwater, PA) was evaluated in a double-blind, randomized, controlled clinical trial conducted in 1021 participants aged 11-17 years. One group received Td and Menactra (polysaccharide diphtheria toxoid conjugate vaccine) vaccines (at separate injection sites) at Day 0 and a saline placebo 28 days later (N=509). The other group received Td and a saline placebo at Day 0 and Menactra (polysaccharide diphtheria toxoid conjugate vaccine) vaccine 28 days later (N=512). Sera were obtained approximately 28 days after each respective vaccination. As shown in Table 5, for meningococcal serogroups C, Y and W-135, the proportion of participants with a 4-fold or greater rise in SBA-BR titer was higher when Menactra (polysaccharide diphtheria toxoid conjugate vaccine) vaccine was given concomitantly with Td than when Menactra (polysaccharide diphtheria toxoid conjugate vaccine) vaccine was given one month following Td. The clinical relevance of this finding has not been fully evaluated. No interference was observed in the immune response to the tetanus and diphtheria components following concomitant vaccination (see Table 5 and DOSAGE AND ADMINISTRATION section).¹³

Table 5:  Comparison of Antibody Responses for Td* and Menactra (polysaccharide diphtheria toxoid conjugate vaccine) Vaccinesfor Participants Aged 11-17 Years on Day 28 Following Respective Vaccinations

Typhoid Vi Polysaccharide Vaccine, Typhim Vi®

The concomitant use of Menactra (polysaccharide diphtheria toxoid conjugate vaccine) vaccine and Typhim Vi vaccine (recommended for certain travelers) was evaluated in a double- blind, randomized, controlled clinical trial conducted in 945 participants aged 18-55 years. One group received Typhim Vi vaccine and Menactra (polysaccharide diphtheria toxoid conjugate vaccine) vaccine (at separate injection sites) at Day 0 and a saline placebo 28 days later (N=469). The other group received Typhim Vi vaccine and a saline placebo at Day 0 and Menactra (polysaccharide diphtheria toxoid conjugate vaccine) vaccine 28 days later (N=476). Sera were obtained approximately 28 days after each respective vaccination. The immune response to Menactra (polysaccharide diphtheria toxoid conjugate vaccine) vaccine and to Typhim Vi vaccine when given concurrently was comparable to the immune response when Menactra vaccine or Typhim Vi vaccine was given alone (see Table 6 and DOSAGE AND ADMINISTRATION section).¹³

Table 6:  Comparison of Antibody Responses for Typhim Vi* and Menactra (polysaccharide diphtheria toxoid conjugate vaccine) † Vaccinesfor Participants Aged 18-55 Years on Day 28 Following Respective Vaccinations

REFERENCES

4. Granoff DM, et al. Meningococcal Vaccines. Plotkin SA, Orenstein WA, eds. Vaccines 4th ed. Philadelphia: WB Saunders Co 2004:960.

5. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Prevention and Control of Meningococcal Disease and Meningococcal Disease and College Students. MMWR 2000;49(RR-7).

6. Rosenstein NE, et al. Meningococcal Disease. N Engl J Med 2001;344:1378-1388.

7. World Health Organization (WHO). Group A and C meningococcal vaccines. Wkly Epidemiol Rec 1999;74:297-303.

8. Brassier N, et al. Meningococcal meningitis and meningococcemia: epidemiological study, France (1985-1991). Med Maklad Infect 1995;25:584-593.

9. Sorensen HT, et al. Outcome of Pre-hospital Antibiotic Treatment of Meningococcal Disease. J Clin Epidemiol 1998;51:717- 721.

10. Makela PH, et al. Evolution of conjugate vaccines. Expert Rev Vaccines 2002;1(3):399-410.

11. Goldschneider I, et al. Human immunity to the meningococcus. I. The Role of Humoral Antibodies. J Exp Med 1969; 129:1307-1326.

12. Maslanka SE, et al. Standardization and a Multilaboratory Comparison of Neisseria meningitidis Serogroup A and C Serum Bactericidal Assays. Clin and Diag Lab Immunol 1997;156-167.

13. Data on file, Sanofi Pasteur Inc. - 092503.

14. Department of Health and Human Services (DHHS), Food and Drug Administration (FDA). Biological Products; Bacterial vaccine and toxoids; Implementation of efficacy rule; Proposed Rule. Federal Register December 13, 1985;50(240);51002- 51117.

15. CDC. General recommendations on immunization. Recommendations of the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Family Physicians (AAFP). MMWR 2002;51(RR02):1-36.

Last reviewed on RxList: 10/30/2007
This monograph has been modified to include the generic and brand name in many instances.