The Maternal Group B Streptococcus Alpha-Like Protein Subunit Vaccine GBS-NN Targets Homotypic and Heterotypic Strains, Confers Opsonophagocytic Killing and Prevents <i>in vitro</i> Invasion of Human Epithelial Cells

Abstract

Maternal vaccination, resulting in transfer of protective IgG across the placenta, represents a promising strategy to prevent neonatal disease caused by group B Streptococcus (GBS). The prototype vaccine GBS-NN, a fusion protein consisting of the N-terminal domains of the alpha-like protein (Alp) family members AlphaC and Rib, has been shown to display a good safety profile and to elicit a strong antibody response against the intact GBS-NN protein in a randomized placebo-controlled double-blind phase 1 trial in healthy adult women. Here we show that the vaccinees achieve robust IgG and IgA responses against both AlphaC and Rib and that vaccination additionally gives rise to antibodies against the heterotypic Alp family members Alp1-3. Responses against the heterotypic N-domains were more variable between subjects and correlated strongly with levels of pre-existing antibodies. Postvaccination sera mediated opsonophagocytic killing that correlated strongly with IgG but not IgM responses elicited by the vaccine. These sera also consistently prevented bacterial invasion of human cervical epithelial cells. Like the vaccine-induced response, naturally acquired IgG against the N-domains of AlphaC and Rib was dominated by the IgG1 subclass. Consistent with the enhanced ability of IgG1 to cross the placenta, naturally acquired IgG against both domains accumulated in neonatal relative to maternal blood, as assessed in a separate group of non-vaccinated pregnant women and their babies.