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Human immune response to various doses of group Y and W135 meningococcal polysaccharide vaccines
Abstract:
A divalent vaccine containing equal weights of Neisseria meningitidis group Y and group W135 capsular polysaccharides was inoculated subcutaneously into groups of 32 military recruit volunteers at doses of 10, 25, 50, and 100 micrograms in 10-microliter/microgram volumes. At 4 weeks, the two higher doses induced significantly greater binding antibody responses than did the two lower doses. Differences in response were not found between the two higher doses or between the two lower doses. An additional 32 volunteers received a dose of 25 micrograms in a 20-microliter/microgram volume. Binding antibody response to this vaccine did not differ from the response to doses of 10 and 25 microgram in 10-microliter/microgram volumes. In contrast, bactericidal antibody responses did not differ among doses. Bactericidal antibody was induced in 100% of individuals with low (greater than 4 log2) preexisting serum bactericidal activity, regardless of dose. Bactericidal antibody nonresponse was restricted to individuals with high preexisting serum bactericidal titers. The discrepant dose response between binding and bactericidal antibody resulted from the induction of nonlytic antibody by the higher doses. We conclude that there are no advantages to doses in excess of 5 micrograms of these two chemically similar polysaccharides for the target population of young adult military recruits.
Insights
Higher doses of a meningococcal vaccine showed increased binding antibodies but not bactericidal antibodies in military recruits. Doses over 5 micrograms offer no additional benefit for this population.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- Neisseria meningitidis poses a significant threat, particularly to young adults in close-proximity settings like military training.
- Meningococcal vaccines targeting serogroups Y and W135 are crucial for preventing invasive disease.
Purpose of the Study:
- To evaluate the dose-response relationship of a divalent Neisseria meningitidis vaccine (groups Y and W135) in military recruits.
- To assess both binding and bactericidal antibody responses to varying vaccine doses.
Main Methods:
- A subcutaneous inoculation study involving 64 military recruits.
- Administration of a divalent vaccine at doses of 10, 25, 50, and 100 micrograms.
- Measurement of binding and bactericidal antibody titers at 4 weeks post-vaccination.
Main Results:
- Higher vaccine doses (50 and 100 micrograms) induced significantly greater binding antibody responses compared to lower doses (10 and 25 micrograms).
- No significant differences in binding antibody responses were observed between the two higher doses or the two lower doses.
- Bactericidal antibody responses did not differ significantly across the tested doses, with 100% response in individuals with low pre-existing titers.
Conclusions:
- Doses exceeding 5 micrograms of this divalent meningococcal polysaccharide vaccine do not provide additional advantages for young adult military recruits.
- The induction of nonlytic antibodies at higher doses may explain the discrepancy between binding and bactericidal antibody responses.
- Optimal dosing strategies should consider both binding and functional (bactericidal) antibody induction.