Immunization with a single-repeat alpha C protein may prevent escape of lower repeat mutants of group B Streptococcus.

Abstract

Group B streptococci (GBS) are the leading cause of meningitis, pneumonia, and sepsis in neonates1. The alpha C protein, a protective surface protein is found in > 90% of non-serotype-III GBS. The prototype alpha C protein contains 9 identical tandem repeats5; clinical isolates of GBS showed variable number of repeats3. Previously, we showed in a mouse model that GBS with lower repeat number could escape the immune system when immunized with 9-repeat-elicited antiserum4. ELISA inhibition, using purified alpha C protein, indicated that 9- and 16-repeat-elicited antibodies recognize conformational epitopes present in higher repeat, but absent in lower repeat alpha C protein2. This may explain escape of the lower repeat mutants. Simultaneously, we observed equal binding affinities of 1- and 2-repeat-elicited antisera to all alpha C proteins, independent of their repeat number. This suggested that 1- and 2-repeat-elicited antibodies may prevent escape of lower repeat mutants. To study the importance of the repeat number for vaccine use, we immunized mice passively with rabbit antisera elicited to 1-, 2-, 9-, and 16-repeat alpha C protein and challenged their neonates with GBS strain A909 (expressing 9 repeats). We determined protection levels and analyzed the repeat number of the escape mutants, isolated from the spleens of these neonates, by western blotting.KeywordsRepeat NumberRabbit AntiserumStreptococcal InfectionBlood Agar PlateEscape MutantThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.