Identification of a universal Group B streptococcus vaccine by multiple genome screen

Abstract

Group B Streptococcus (GBS) is a multiserotype bacterial pathogen representing a major cause of life-threatening infections in newborns. To develop a broadly protective vaccine, we analyzed the genome sequences of eight GBS isolates and cloned and tested 312 surface proteins as vaccines. Four proteins elicited protection in mice, and their combination proved highly protective against a large panel of strains, including all circulating serotypes. Protection also correlated with antigen accessibility on the bacterial surface and with the induction of opsonophagocytic antibodies. Multigenome analysis and screening described here represent a powerful strategy for identifying potential vaccine candidates against highly variable pathogens.

Fig. 1

Opsonophagocytic activity of sera specific for vaccine antigens. Live GBS bacteria of strain CJB111 were incubated for 1 hour with human PMNs in the presence of baby rabbit complement and specific antisera. The log₁₀ of the difference between bacterial colony forming units at time = 0 and time = 1 hour are shown. Values for preimmune sera are negative because of bacterial growth during the assay. The antigens used are recorded above each bar. Shaded bars represent specific immune sera; open bars, the corresponding preimmune sera from the same animals. Error bars indicate standard deviation.