Forward and reverse translational approaches to predict efficacy of neutralizing respiratory syncytial virus (RSV) antibody prophylaxis

Respiratory syncytial virus prevention within reach: the vaccine and monoclonal antibody landscape

“…108 A human challenge trial 109 (n=80) showed reduced viral load after viral challenge and reduced RSV symptomatic infection rates. A meta-analysis 110 was done to assess the relationship between serum neutralising antibodies and clinical endpoints; the study estimated a single 75 mg dose would have more than 75% efficacy lasting 5 months in term infants. The company developing this agent has committed to helping navigate uncertainty and improving issues of access through ongoing research and innovation to help address the burden of potentially preventable childhood diseases (Andrew W Lee, Merck, personal communication).…”

Upper and lower respiratory tract correlates of protection against respiratory syncytial virus following vaccination of nonhuman primates

“…Specifically, prophylaxis with neutralizing mAb therapeutics has been associated with a reduction in hospitalizations while higher neutralizing-antibody titers are associated with the greatest reduction in disease (Claydon et al, 2017;Piedra et al, 2003). Additionally, recent meta-analyses integrating data related to antibody-binding titers, serum-neutralization titers, and T cell immunity from various prophylactic treatments found neutralization to be a predictor of protection against RSV (Maas et al, 2021), although prediction does not imply mechanistic causality. However, even though several RSV vaccines have been developed that are able to induce neutralizing antibodies, no licensed vaccine is currently available, perhaps related to the strict focus on antibody titers and neutralizing antibodies.…”

Monoclonal antibodies for prophylaxis and treatment of respiratory viral infections

“…Neutralization potency is traditionally considered one of the strongest correlates of protection against respiratory viral infection, particularly in the upper respiratory tract [17 ▪ –19 ▪ ]. Neutralizing antibody titers can predict clinical efficacy of mAbs against RSV and potentially other respiratory viruses [20 ▪ ]. Therefore, high neutralization potency – in which a relatively low concentration of mAb is needed to prevent viral infection in vitro – is considered a desirable property.…”