N19 polyepitope as a carrier for enhanced immunogenicity and protective efficacy of meningococcal conjugate vaccines

Abstract

N19, a string of human universal CD4 T-cell epitopes from various pathogen-derived antigens, was shown to exert a stronger carrier effect than CRM197 for the induction of anti-group C Neisseria meningitidis capsular polysaccharide (MenC), after immunization of mice with various dosages of N19-MenC or CRM-MenC conjugate vaccines. After two immunizations, the N19-based construct induced anti-MenC antibody and protective bactericidal antibody titers higher than those induced by three doses of the CRM-MenC conjugate and required lower amounts of conjugate. N19-based conjugates are superior to CRM-based conjugates to induce protective immune responses to MenC conjugates.

FIG. 1.

Serum anti-MenC IgG antibody responses. Groups of six BALB/c mice were immunized three times with decreasing amounts of N19-MenC or CRM-MenC (2.5, 0.625, 0.156, and 0.039 μg of MenC/dose) and 0.5 mg of aluminium hydroxide. Serum samples were collected before (pre) and after (post-1, -2, and -3) each immunization and tested individually to quantitate MenC-specific IgG antibody titers. Each point represents the mean antibody titer (± 1 SD) of each group at each time point.

FIG. 2.

Anti-carrier IgG antibody responses in single serum samples of mice immunized as described before. Since mice were immunized with equal amounts of MenC in either conjugate, the final amount of carrier protein is slightly different in the groups receiving the CRM-MenC and those that received the N19-MenC, due to the slight difference in the sugar-to-protein ratios in the two constructs. Serum samples were collected before (pre) and after (post-1, -2, and -3) each immunization and tested individually to quantitate carrier-specific IgG antibody titers. Each point represents the mean antibody titer (± 1 SD) of each group at each time point.

FIG. 3.

Bactericidal activity in serum samples of mice immunized three times with decreasing amounts of N19-MenC or CRM-MenC (2.5, 0.625, 0.156, and 0.039 μg of MenC/dose) and 0.5 mg of aluminium hydroxide. Bactericidal antibody titers from pooled serum samples collected before (pre) and after (post-1, -2, and -3) each immunization are shown. Results are expressed as reciprocal values of the highest serum dilution giving at least 50% bacterial killing.