Multivalent group A streptococcal vaccine elicits bactericidal antibodies against variant M subtypes

Abstract

Group A streptococci cause a wide spectrum of clinical illness. One of several strategies for vaccine prevention of these infections is based on the type-specific M protein epitopes. A multivalent M protein-based vaccine containing type-specific determinants from 26 different M serotypes is now in clinical trials. Recent epidemiologic studies have shown that, within some serotypes, the amino-terminal M protein sequence may show natural variation, giving rise to subtypes. This raises the possibility that vaccine-induced antibodies against the parent type may not be as effective in promoting bactericidal killing of variant subtypes. In the present study we used rabbit antisera against the 26-valent M protein-based vaccine in bactericidal tests against M1, M3, and M5 streptococci, which were represented by multiple subtypes. We show that the vaccine antibodies effectively promoted in vitro bactericidal activity despite the fact that the M proteins contained naturally occurring variant sequences in the regions corresponding to the vaccine sequence. Our results show that the variant M proteins generally do not result in significant differences in opsonization promoted by rabbit antisera raised against the 26-valent vaccine, suggesting that a multivalent M protein vaccine may not permit variant subtypes of group A streptococci to escape in a highly immunized population.

FIG. 1.

In vitro bactericidal tests performed with rabbit antisera against the 26-valent M protein-based group A streptococcal vaccine and subtypes of M1 (A), M3 (B), and M5 (C). Percent kill (±standard error of the mean) was calculated based on the formula provided in Materials and Methods. The number within the base of each bar indicates the number of assays performed for each strain. *, statistically significant difference (P < 0.001) compared to the result obtained with M1.0 based on a one-way analysis of variance.