AbstractA novel Group B Streptococcus (GBS) vaccine, based upon the GBS alpha‐like surface proteins, is being developed by MinervaX for administration to pregnant women. The vaccine is intended to generate antibodies (IgG) capable of crossing the placenta, in order to passively immunize the baby and provide protection in utero and up to 3 months after birth. An initial vaccine candidate, GBS‐NN (based on the N‐terminal domains of Rib and AlphaC surface proteins) was replaced, due to insufficient cross‐reactivity with the two other N‐terminal proteins (Alp1 and Alp2/3), by a modified vaccine candidate designated GBS‐NN/NN2 that included all four AlpNs. Preclinical studies raised no safety concerns and the subsequent Phase I clinical trial demonstrated that the vaccine was well tolerated and strongly immunogenic. As the vaccine is intended for use during pregnancy for maternal immunization, an embryofetal study in rats and a fertility and embryofetal study in rabbits were performed, in both cases using GBS‐NN/NN2. Vaccination of female rats or rabbits did not adversely affect embryofetal development or survival in either species, or mating or fertility in rabbits. In both studies, the pregnant animals developed immune responses to GBS‐NN and GBS‐NN2 proteins and concentrations of antibodies to both fusion proteins were detected in the fetuses and in the amniotic fluid. Data generated during these reproductive studies indicated a suitable safety margin (approximately 40‐fold clinical dose) considered appropriate to support a subsequent human trial of GBS‐NN/NN2 administered in the second and third trimesters of pregnancy.
