Intrapartum antibiotic prophylaxis (IPA) during labor for women identified as having recto-vaginal Groups B Streptococcus (GBS) colonization, has been successful in preventing early-onset invasive (<7 days of age) disease in new-borns in high income countries where implemented. Nevertheless, GBS remains a leading cause of neonatal sepsis in high-income settings, and is now also the leading cause of bacterial meningitis in USA. Also, the incidence of invasive GBS disease remains high in sub-Saharan African countries, where IAP is not feasible, whilst its contribution to neonatal sepsis is uncertain in South Asia. Furthermore, recent data indicate that the burden of GBS associated stillbirths might be similar to that for EOD in some African countries. Recent advances in the prevention of invasive GBS disease during early infancy, including the potential to prevent late onset disease (7-89 days age) which is not preventable by IAP, is the development of polyvalent polysaccharide protein conjugate vaccines. Recent studies have reported on the safety and immunogenicity of a trivalent (serotypes Ia, Ib and III) GBS polysaccharide protein conjugate vaccine (GBS-3CV). This vaccine elicits immune responses in pregnant women vaccinated during the last trimester, albeit less so among women in whom the pre-vaccination antibody titers were less than the lower detection limit of the assay. The ratio of antibody transfer to the newborns’ of these women was approximately 0.5-0.7, indicating less efficient transplacental transfer of polysaccharide targeted IgG than is observed for IgG targeted at protein antigens. Furthermore, vaccination of HIV-infected women, elicited lower quantitative antibody responses than in HIV-uninfected women, suggesting the need for different vaccine schedules in these women. Also, the GBS conjugate vaccine appears to be more immunogenic in African than European/North American women. The licensure of a GBS vaccine for pregnant women aimed at protection against invasive GBS disease of their newborns will, however, require sample size in excess of 70,000 participants for an invasive disease endpoint. An alternate licensure pathway, as is the case for meningococcal vaccine, could be premised on establishing a sero-correlate of protection against invasive disease and using this to license the vaccine based on immunogenicity and safety.