Week 3, November 2024: Infant RSV

Respiratory Syncytial Virus (RSV) is a leading cause of severe respiratory infections, particularly in infants, the elderly, and immunocompromised individuals. Despite its global prevalence, there has historically been a lack of effective therapeutic options for high-risk populations. Advances in antibody drug discovery have paved the way for innovative treatments, offering targeted approaches to neutralize RSV. Monoclonal antibodies, with their ability to bind specifically to the RSV fusion (F) protein, are transforming how we prevent and manage this virus. Here we highlight recent research advances.

Researchers from Fred Hutch Cancer Center have developed a new anti-idiotype antibody as a first step in possible strategy to build infant immunity during their vulnerable window. Antibodies derived from VH3-21/VL1-40 gene paring are hardwired to neutralize RSV without the need for affinity maturation, making them attractive to target through vaccination. Here, they develop a bispecific anti-idiotypic antibody (ai-mAb) to target VH3-21/VL1-40 B cell receptors (BCRs). The ai-mAb efficiently engages B cells encoding RSV-neutralizing antibodies. These results establish proof of concept for using an ai-mAb-derived vaccine to target B cells hardwired to produce RSV-neutralizing antibodies.

Meanwhile, a recent study reveals that maternal RSV vaccination timing is key to safeguarding newborns, with vaccination early in the approved window (≥ 5 weeks prior to delivery) allowing for the most efficient placental transfer of maternal antibody. This analysis adds needed data about transplacental antibody transfer efficiency week-by-week after maternal RSV vaccination, suggesting that clinical guidance for vaccination timing within the approved window may need to be refined to optimize neonatal protection.

In exciting news, Merck Group’s RSV shot for infants (Clesrovimab) showed promise from Phase 2b/3 trial results and could be available in 2025. Clesrovimab is an investigational RSV preventative extended half-life monoclonal antibody that was 91% effective at preventing medically attended lower respiratory tract infections vs. Placebo. It is designed to be administered as the same single dose, regardless of birth weight. One dose of clesrovimab performed similarly to five doses of palivizumab among high-risk infants.