Functional longevity of maternally derived antibodies against group B Streptococcus and respiratory syncytial virus in HIV-exposed uninfected and HIV-unexposed uninfected infants. - Group B streptococcus (GBS) and respiratory syncytial virus (RSV) are the primary causes of neonatal and infant deaths with HIV-exposed uninfected infants bearing the highest brunt of disease. Although there are no licensed vaccines against GBS and RSV, maternal vaccines are currently being developed and some promising candidates are completing phase III clinical trials. Maternal vaccines are considered the optimal strategy to prevent disease in both pregnant women and their respective infants. However, due to the low incident rate per study setting for GBS, determining vaccine efficacy via phase III clinical trials could be logistically infeasible. Therefore, to expedite vaccine licensure and implementation, an alternative pathway would be to conduct immuno-bridging studies to establish antibody concentrations correlated with disease protection as targets to measure vaccine immunogenicity in these vulnerable populations. HIV infection impairs B cell immunity leading to the generation of defective antibodies. This could therefore ultimately impact the efficacy of maternal vaccines against GBS and/or RSV in conferring protection to infants including those that are HIV-exposed but uninfected. Since 95-99% of infant mortality cases related to GBS and RSV occur in low-middle income countries (LMIC) where HIV infection is prevalent, it is crucially important to consider how this would impact antibody thresholds and functional longevity required to confer protection to the young. Moreover, clinical epidemiological studies report higher incidence of mortality cases amongst HIV- exposed uninfected infants (iHEU) attributable to GBS and RSV diseases compared to HIV-unexposed uninfected infants (iHUU). iHEU account for 20-30% of newborns in LMIC with ~1 million iHEU born each year. To ensure that this vulnerable infant population is protected by the maternal vaccines being developed, immunological parameters that could influence passive immunity in mother-infant pairs need to be established for consideration when evaluating GBS and RSV immunogenicity in clinical trials. Although there is consensus evidence that trans-placental antibody transfer is poor in iHEU compared to iHUU, there are a limited studies reporting the kinetic profile and functionality of these transferred antibodies, and with even fewer studies describing how HIV infection impacts breast milk antibodies against GBS and RSV. Using an existing longitudinal INFANT cohort consisting of plasma and breastmilk samples, we propose to quantify mother-infant antibody concentrations and functional kinetics to determine whether they are compromised by HIV-infection (mother) or HIV-exposure (infant); information that is currently missing in existing literature. Our study therefore proposes to use multiplex immunoassays to measure and compare antibody concentrations, avidity, and function against GBS and RSV between iHEU and iHUU to establish parameters to be achieved for an effective maternal vaccine in high HIV endemic regions.
