A randomized trial to determine the tolerability and immunogenicity of a quadrivalent meningococcal glycoconjugate vaccine in healthy adolescents.

ABSTRACT

BACKGROUND: Because of the well-documented increased risk of meningococcal disease among adolescents, vaccination is recommended for this population in many countries, including the United States. This study compared the tolerability and immunogenicity in adolescents of a candidate quadrivalent meningococcal CRM197 glycoconjugate vaccine against serogroups A, C, W-135, and Y (MenACWY-CRM) with that of the licensed unconjugated quadrivalent polysaccharide vaccine (MPSV4). METHODS: This phase II study was conducted in the United States among 524 adolescents aged 11-17 years in 2 stages, with different randomization schemes. The first 334 participants, enrolled in Stage 1, were randomized (11) to receive either MenACWY-CRM(+) (with adjuvant) or MPSV4. The next 190 participants, enrolled in Stage 2, were randomized (41) to receive either MenACWY-CRM(-) (without adjuvant) or MPSV4. Safety data were collected using diary cards and active surveillance. Human complement serum bactericidal activity (hSBA) titers were measured 1 and 12 months postvaccination. RESULTS: MenACWY-CRM and MPSV4 vaccines were well tolerated (local reactions, 63%-71% vs. 60%-62%; systemic reactions, 44%-56% vs. 46%-59%, respectively). One month postvaccination, similar hSBA titers were observed with the adjuvanted and nonadjuvanted MenACWY-CRM. The immunogenicity of MenACWY-CRM(-), measured by geometric mean titer, was significantly (P < 0.05) greater than that of MPSV4 for all 4 vaccine serogroups at 1 month. The percentage of subjects with hSBA titers > or =14 was also significantly greater (P < 0.01) for MenACWY-CRM(-) recipients for serogroups A, C, and Y and noninferior for W-135. The proportions of MenACWY-CRM(-) recipients with hSBA titers > or =14 to the vaccine serogroups at 1 month were 84% to 96% and geometric mean titers were 34 to 100. The percentage of subjects with hSBA titers > or =14 was significantly (P < 0.01) greater than MPSV4 for serogroups C, W-135, and Y 12 months postvaccination. CONCLUSIONS: MenACWY-CRM was well tolerated and immunogenic, with evidence of persistence of bactericidal antibodies for at least 12 months postvaccination.