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.
