Maternal Vaccination to Prevent Neonatal and Infant Infection

Despite recent declines in childhood mortality, approximately 7 million children under 5 years of age die each year; almost half occur in the first 28 days of life. It is estimated that close to 1 million of these neonatal deaths are due to infection and are largely concentrated in developing regions. For infections occurring so early in life, before a window of vaccination for the infant, vaccination of the mother is pursued. This strategy is best exemplified for neonatal tetanus with resulting near eradication in many target nations. Millions of women worldwide have received tetanus vaccination during pregnancy with significant benefit and without systemic or reproductive toxicity to mother or fetus. Novartis Vaccines & Diagnostics (NVD) is pursuing maternal vaccination for the prevention of key neonatal pathogens including group B streptococcus (GBS). GBS is a leading cause of newborn bacterial infections in developed regions and studies in Southern Africa, Kenya and Asia have similarly demonstrated the importance of GBS in global locations. Accordingly, NVD has developed a vaccine consisting of GBS capsular polysaccharide glycoconjugates intended for administration to mothers during the second half of pregnancy. Initial clinical trials have shown the vaccine to be well-tolerated and immunogenic in non-pregnant women, supporting advancement to studies in pregnant women. Ph II studies in pregnant women are ongoing in Europe, Canada, South Africa and Malawi. These studies will examine GBS-specific antibody responses induced in pregnant women and their infants, including women with and without HIV infection. These studies are intended to support a large Ph III trial to determine the efficacy of the Novartis GBS vaccine in the prevention of newborn GBS infection. By harnessing the potential of the mother to passively protect her infant, maternal vaccination strategies are expected to be a critical factor in reducing infant mortality in the youngest infants.