Quantifying the association between neutralising antibodies and protection from RSV disease in infants and adults: A systematic review and meta-analysis

A number of vaccines and long-acting monoclonal antibodies have been shown to be effective in the prevention of respiratory syncytial virus (RSV) disease. However, an immune correlate of protection for RSV has not yet been identified. We conducted a systematic review to identify published reports of immunogenicity and/or efficacy in vaccines and long-acting monoclonal antibodies against RSV and performed a meta-analysis on extracted data to identify any relationship between antibody increase and protection against RSV disease. We identified 130 relevant reports which we classified into an open access evidence map of RSV immunisation products. We found a strong correlation between the immunisation induced rise in neutralising antibody titres and efficacy ({rho}>0.7 for all comparisons, Spearman). For infants, we estimated that each 10-fold increase in neutralising antibody titre rise provides an additional 31% [95% CI 10%-47%], 47% [95% CI 36%-56%] and 57% [95% CI 45%-66%] reduction in the relative risk of symptomatic, moderate and severe disease respectively. For older adults, a 10-fold rise in antibody levels was associated with a 34% [95% CI -2%-57%], 50% [95% CI 22%-67%] and 63% [95% CI 36%-79%] reduction in the relative risk of RSV disease with 1, 2 and 3 symptoms respectively. These results align extremely well with findings from natural history studies and individual-based analysis of correlates of protection studies. This work paves the way for use of neutralising antibodies as a correlate of protection to guide the development, approval, and deployment of RSV vaccines and monoclonal antibodies.