Biological factors that may impair transplacental transfer of RSV antibodies: Implications for maternal immunization policy and research priorities for low- and middle-income countries

Respiratory syncytial virus (RSV) is the leading viral cause of acute lower respiratory tract infection (ALRI), including bronchiolitis and pneumonia, in infants and children worldwide. Protection against RSV is primarily antibody mediated and passively acquired RSV neutralizing antibody can protect infants from RSV ALRI. Maternal immunization is an attractive strategy for the prevention of RSV in early infancy when immune responses to active immunization may be suboptimal and most severe RSV disease and death occur. However, several biologic factors have been shown to potentially attenuate or interfere with the transfer of protective naturally acquired antibodies from mother to fetus and could therefore also reduce vaccine effectiveness through impairment of transfer of vaccine-induced antibodies. Many of these factors are prevalent in low- and middle-income countries (LMIC) which experience the greatest burden of RSV-associated mortality; more data are needed to understand these mechanisms in the context of RSV maternal immunization. This review will focus on what is currently known about biologic conditions that may impair RSV antibody transfer, including preterm delivery, low birthweight, maternal HIV infection, placental malaria, and hypergammaglobulinemia (high levels of maternal total IgG). Key data gaps and priority areas for research are highlighted and include improved understanding of the epidemiology of hypergammaglobulinemia and the mechanisms by which it may impair antibody transfer. Key considerations for ensuring optimal vaccine effectiveness in LMICs are also discussed.