Correlates of Protection Against Respiratory Syncytial Virus Infection in Infancy

The highest morbidity and mortality from respiratory syncytial virus (RSV) infection occurs in young infants. Immunization of expectant mothers during pregnancy has the potential to substantially reduce the burden of RSV disease in a majority of infants. Correlates of protection (COP) are important in guiding the development of maternal RSV vaccines and the design of maternal RSV vaccine trials, as immune response to candidate vaccines should mirror protective RSV immunity at birth. Here, we review the literature reporting correlations between RSV immune measures at birth and clinical RSV outcomes during infancy. Less than a dozen studies have investigated immunological COP with RSV disease or related hospitalization, yielding inconsistent findings overall. The differences in findings between studies could be due to differences in inclusion/exclusion criteria (e.g., the inclusion of older infants who may benefit less from maternal antibodies or infants followed during inter-seasonal periods where RSV is absent), differences in semi-quantitative RSV antibody neutralization assays, or differences in RSV outcome measures such as the sensititivity/specificity of diagnostic tests. Future research in this field should seek to standardize RSV immunological measures and outcomes, expand the breadth of functional RSV measures beyond antibody neutralization, and consider infants’ age and seasonality of RSV infection.