RECOMBINANT ATTENUATED SALMONELLA VACCINE (RASV) VACCINATION in NEONATAL MICE is ENHANCED by ANTIGEN SPECIFIC ANTIBODIES

We have developed a live oral recombinant attenuated Salmonella vaccine (RASV) encoding a Streptococcus pneumoniae antigen that is safe, immunogenic, and provides protection to lethal challenge in adult mice and pups (neonates and infants). Vaccinated adult female mice produce antigen-specific antibodies on mucosal surfaces, blood, and, after birthing pups, in their milk. Immunogenicty of the RASV in pups is linked to the mother’s immunization state; RASV vaccinated pups of RASV vaccinated mothers resulted in higher levels of antigen-specific antibodies at 3 and 5 weeks post vaccination in fecal pellets and blood compared to RASV vaccinated pups of vector-control vaccinated mothers.  The antigen-specific antibodies measured in the pups are produced by the pups, not maternal antibody from the mothers, as demonstrated by the buffer control pups of RASV vaccinated mothers. We evaluated the respective contributions of prenatal and postnatal antibody transfer on the immunogenicity of the RASV in pups by swapping pups from the litters of RASV vaccinated and vector-control mothers. Our findings indicate that immunity in pups is associated more strongly with receiving postnatal antibodies than prenatal antibodies, and we propose that the postnatal SIgA against the RASV is responsible. These findings have several implications for successful vaccination of neonates.