Maternal vaccination against group B Streptococcus glyceraldehyde-3-phosphate dehydrogenase leads to gut dysbiosis in the offspring

Group B Streptococcus (GBS) remains a major neonatal life-threatening pathogen. We initially identified glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a promising vaccine candidate against GBS. Since GAPDH is highly conserved, we investigate whether GBS GAPDH maternal vaccination interferes with the intestinal colonization of the offspring and the development of its mucosal immune system and central nervous system. An altered gut microbiome with increased Proteobacteria is observed in pups born from vaccinated dams during early life. These pups present decreased relative expression of IL-1β, IL-17A, RegIIIγ and MUC2 in the distal colon. They also display increased CD11b, F4/80 and MHC class II expression on microglia in early life and marked reduction of Ly6C⁺ cells and neutrophils. Importantly, male mice born from vaccinated mothers present behavioral abnormalities during adulthood, including decreased exploratory behavior, a subtle anxious-like phenotype and global alterations in spatial learning and memory strategies, and higher sensitivity to a stressful stimulus. Our study highlights the danger of using ubiquitous antigens in maternal human vaccines against neonatal pathogens.