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.

Avidity of Serogroup A Meningococcal IgG Antibodies after Immunization with Different Doses of a Tetravalent A/C/Y/W135 Polysaccharide Vaccine

“…Although there are practical challenges to the use of reduced doses in the field, our findings suggest that reduced doses of polysaccharide vaccine are able to elicit antibodies of as good avidity against serogroup A polysaccharide as a full dose. young adults in the United States in the 1970s and 1980s showed that lower doses of polysaccharide were as effective as 50 lg in inducing serum bactericidal antibody levels that are assumed to be protective against meningococcal disease [10,11]. We have previously shown that the same is true in African children and teenagers for serogroup A, Y and W135 [12], with 1 ⁄ 5 of the dose (10 lg) inducing similar levels of bactericidal antibodies as a full dose (50 lg).…”

Protection against meningococcal serogroup ACYW disease in complement-deficient individuals vaccinated with the tetravalent meningococcal capsular polysaccharide vaccine

“…Because of the high risk of (recurrent) meningococcal disease, it has been recommended to vaccinate complement-deficient individuals against meningococcal disease [2][3][4]. The meningococcal vaccine available, consisting of polysaccharides from serogroups A, C, W135 and Y, provides protection for a restricted period of about 3 years in complement-sufficient persons, since it is unable to activate T helper cells and to induce memory [8][9][10][11][12][13]. A polysaccharide vaccine against meningococcus serogroup B, the most frequent isolated meningococcal pathogen in Europe and the USA, is not available.…”

Elaboration of a 3.6-kilodalton lipooligosaccharide, antibody against which is absent from human sera, is associated with serum resistance of Neisseria gonorrhoeae

“…We modified a previously described solid-phase radioimmunoassay (39) to detect the presence of antibodies of the same specificities as those of the McAbs in the sera of 40 military recruits who declined to participate in a field trial of an experimental meningococcal vaccine (11). The method was essentially similar to the enzyme-linked immunosorbent assay inhibition technique of Sarafian et al (24).…”