Menactra Mechanism of Action

Pharmacology: Mechanism of Action: The presence of bactericidal anti-capsular meningococcal antibodies has been associated with protection from invasive meningococcal disease. Menactra vaccine induces the production of bactericidal antibodies specific to the capsular polysaccharides of serogroups A, C, Y and W-135.
Clinical Studies: 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). The response to Menactra vaccination administered to children 9 months through 10 years of age was evaluated by the proportion of participants 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 Menactra vaccination was evaluated by the proportion of participants with a 4-fold or greater increase in baseline 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).
Immunogenicity: Immunogenicity in Children 9 through 23 Months of Age: In a randomized, US, multi-center trial, children received Menactra at 9 months and 12 months of age. The first Menactra dose was administered alone, followed by a second Menactra dose given alone (N=404), or with MMRV (N=302), or with PCV7 (N=422). For all participants, sera were obtained approximately 30 days after last vaccination. There were no substantive differences in demographic characteristics between the vaccine groups. The median age for administration of the first dose of Menactra was approximately 9 months. In the primary immunogenicity study, children received Menactra at 9 and 12 months of age, the majority of the participants in groups that received the second dose of Menactra alone or with concomitant pediatric vaccine(s), achieved SBA-HC titers ≥1:8 for all serogroups. Groups that received the second dose of Menactra alone had ≥91% of subjects achieving an SBA-HC titer ≥1:8 for serogroups A, C, and Y and ≥86% for serogroup W-135. When the second dose of Menactra was given concomitantly with MMRV (or MMRV+Hib) or with PCV, the percentages of subjects with SBA-HC titers ≥1:8 were high (>90% for serogroups A, C, and Y and >81% for serogroup W-135). SBA-HC geometric mean titers (GMTs) were high for all serogroups.
An additional study evaluating responses to a 2-dose series of Menactra administered at either 9 and 15 months or at 12 and 15 months of age was conducted. Following the second dose of Menactra in the 9-15 months group, the percentages of participants with hSBA titer ≥1:8 were high for all of the serogroups (>96% for C, Y and W-135 and >85.2% for serogroup A). Similar responses were observed in the 12-15 months group. The percentages of participants with an hSBA titer ≥1:8 were: 85.2% for A; 100.0% for C and >96% for both Y and W-135 serogroups.
Individuals 2 through 55 Years of Age: Immunogenicity was evaluated in three comparative, randomized, US, multicenter, active controlled clinical trials that enrolled children (2 through 10 years of age), adolescents (11 through 18 years of age), and adults (18 through 55 years of age). Participants received a single 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.)
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.
Immunogenicity in Children 2 through 10 Years of Age: Of 1408 enrolled children 2 through 10 years of age, immune responses evaluated by hSBA in a subset of Menactra vaccine participants (2 through 3 years of age, N=52; 4 through 10 years of age, N=84) and Menomune - A/C/Y/W-135 vaccine participants (2 through 3 years of age, N=53; 4 through 10 years of age, N=84), the percentages of subjects with a titer ≥1:8 were constantly higher in the Menactra group for all four serogroups. In the evaluated subset of participants 2 through 3 years of age, the percentage of participants with an hSBA titer ≥1:8 at Day 28 were 73%, Serogroup A; 63%, Serogroup C; 88%, Serogroup Y; 63%, Serogroup W-135 in the Menactra group and 64%, Serogroup A; 38%, Serogroup C; 73%, Serogroup Y; and 33%, Serogroup W-135 in the Menomune group.
In the evaluated subset of participants 4 through 10 years of age, the percentage of participants with an hSBA titer ≥1:8 at Day 28 were 81%, Serogroup A; 79% Serogroup C; 99%, Serogroup Y; 85%, Serogroup W-135 in the Menactra group and 55%, Serogroup A; 48%, Serogroup C; 92%, Serogroup Y; and 79%, Serogroup W-135 in the Menomune group.
Immunogenicity in Adolescents 11 through 18 Years of Age: Results from the comparative clinical trial conducted in 881 adolescents (aged 11 through 18 years) showed that the immune responses measured by SBA-BR to Menactra vaccine and Menomune - A/C/Y/W-135 vaccine were similar for all four serogroups. The percentage of participants with an SBA-BR titer with a ≥4-fold rise from the baseline were 93%, Serogroup A; 92%, Serogroup C; 82%, Serogroup Y; 97%, Serogroup W-135 in the Menactra group and 92%, Serogroup A; 89%, Serogroup C; 80%, Serogroup Y; and 95%, Serogroup W-135 in the Menomune group.
In participants with undetectable pre-vaccination titers (ie, less than 1:8 at Day 0), seroconversion rates (defined as a ≥4-fold rise in Day 28 SBA-BR titers) were similar between the Menactra vaccine and Menomune - A/C/Y/W-135 vaccine recipients. Menactra vaccine participants achieved seroconversion rates of: 100%, Serogroup A; 99%, Serogroup C; 98%, Serogroup Y; 99%, Serogroup W-135. The seroconversion rates for Menomune - A/C/Y/W-135 vaccine recipients were: 100%, Serogroup A; 99%, Serogroup C; 100%, Serogroup Y; 99%, Serogroup W-135.
Immunogenicity in Adults 18 through 55 Years of Age: Results from the comparative clinical trial conducted in 2554 adults aged 18 through 55 years showed that the immune responses measured by SBA-BR to Menactra vaccine and Menomune - A/C/Y/W-135 vaccine were similar for all four serogroups. The percentage of participants with an SBA-BR titer with a ≥4-fold rise from the baseline were 81%, Serogroup A; 89%, Serogroup C; 74%, Serogroup Y; and 89%, Serogroup W-135 in the Menactra group and 85%, Serogroup A; 90%, Serogroup C; 79%, Serogroup Y; and 94%, Serogroup W-135 in the Menomune group. In participants with undetectable pre-vaccination titers (ie, less than 1:8 at Day 0), seroconversion rates (defined as a ≥4-fold rise in Day 28 SBA-BR titers) were similar between the Menactra vaccine and Menomune - A/C/Y/W-135 vaccine recipients.
Menactra vaccine participants achieved seroconversion rates of: 100%, Serogroup A; 99%, Serogroup C; 91%, Serogroup Y; and 97%, Serogroup W-135. The seroconversion rates for Menomune - A/C/Y/W-135 vaccine recipients were: 99%, Serogroup A; 98%, Serogroup C; 97%, Serogroup Y; and 99%, Serogroup W-135.
Concomitant Vaccine Administration: Td: In a double-blind, randomized, controlled trial, 1021 participants aged 11 through 17 years received Td and Menactra vaccines concomitantly (N=509), or Td followed one month later by Menactra vaccine (N=512). Sera were obtained approximately 28 days after each respective vaccination. The proportion of participants with a 4-fold or greater increase in SBA-BR titer to meningococcal Serogroups C, Y and W-135 was higher when Menactra vaccine was given concomitantly with Td (86-96%) than when Menactra vaccine was given one month following Td (65-91%). Anti-tetanus and anti-diphtheria antibody responses were similar in both study groups.
Typhim Vi (Typhoid Vi Polysaccharide Vaccine): In a double-blind, randomized, controlled trial, 945 participants aged 18 through 55 years received Typhim Vi and Menactra vaccines concomitantly (N=469), or Typhim Vi vaccine followed one month later by Menactra vaccine (N=476). Sera were obtained approximately 28 days after each respective vaccination. The antibody responses to Menactra vaccine and to Typhim Vi vaccine components were similar in both study groups.
Non-Clinical Toxicology: Carcinogenesis, Mutagenesis, Impairment of Fertility: Menactra vaccine has not been evaluated for carcinogenic or mutagenic potential or for impairment of male fertility. A developmental animal toxicity study showed that Menactra had no effects on female fertility in mice (see Use in Pregnancy & Lactation).