Ryan et al. Bifidobacteria support optimal infant vaccine responses

Additional code and data for the publication: Bifidobacteria support optimal infant vaccine responses. Ryan et al. AbstractMounting evidence suggests that antibiotic exposure leads to impaired vaccine responses, however the mechanisms remain poorly understood. Here we prospectively followed 191 healthy, vaginally-born, term infants from birth to 15 months, implementing a systems vaccinology approach to assess the effects of antibiotic exposure on immune responses to vaccination in these infants. Exposure to direct neonatal, but not intrapartum, antibiotics was associated with significantly lower antibody titres against multiple different polysaccharides in the 13-valent pneumococcal conjugate vaccine (PCV13) and the Haemophilus influenzae type b polyribosylribitol phosphate and diphtheria toxoid antigens in the combined 6-in-1 Infanrix hexa® vaccine, at 7 months of age. Infants exposed to neonatal antibiotics had an inflammatory transcriptional profile in blood pre-vaccination and faecal metagenomics revealed reduced Bifidobacteriumin these infants at the time of vaccination, which correlated with reduced vaccine antibody titres 6 months later. In preclinical models, responses to PCV13 were strongly dependent on an intact microbiota but could be restored in germ-free mice by administering a consortium of Bifidobacterium species, or a probiotic already widely used in neonatal units. Our data suggest that microbiota-targeted interventions could mitigate the detrimental effects of early-life antibiotics on vaccine immunogenicity.