Respiratory Syncytial Virus - A Long and Troubled Road

Respiratory syncytial virus (RSV) has recently gained much attention due to the approval of several drugs this year. 

On May 3, 2023, the U.S. Food and Drug Administration (FDA) authorized Arexvy, the first RSV vaccine for use in the United States. A few months later on July 17, 2023, they approved nirsevimab (Beyfortus), a monoclonal antibody (mAb) used to prevent RSV in babies and toddlers. 

Developed by Sanofi and AstraZeneca, Beyfortus is a single-dose long-acting human recombinant mAb that provides passive immunization against RSV by binding to the fusion protein on the surface of the virus. 

This month, a study by Wen et al. found a broadly neutralizing antibody, RSV-199, with the remarkable ability to cross-neutralize both RSV and Human Metapneumovirus (hMPV). RSV-199 engages both RSV and hMPV F proteins through conserved interactions of the antibody heavy-chain variable region. These infections pose a significant health burden in young children and the elderly, so it holds valuable potential as an antibody therapeutic.

Positive RSV detections in the US by week. Source: National Center for Immunization and Respiratory Diseases (NCIRD), Division of Viral Diseases

Before this year, only palivizumab (a humanized monoclonal anti-F antibody) and intravenous RSV-IVIG (polyclonal antibodies) were available to treat RSV. 

Motavizumab was derived from palivizumab as a second-generation mAb using affinity maturation, but was never FDA-approved. Similarly, suptavumab, a fully human mAb, was discontinued due to not meeting its primary endpoint. Thus, research into RSV antibodies remains highly active. 

RSV accounts for up to 60% of hospitalizations due to respiratory infections among young children in the US each year. The virus damages the bones, immune system, kidneys, and red blood cell count, and therapies are needed to overcome developed resistance and decreased effectiveness over time.

Image from DOI: 10.1016/j.vaccine.2016.09.026

As of now, there are two other antibodies in clinical trials for RSV. 

• ALX-0171 is a trivalent single-domain antibody (sdAb) targeting F-hRSV. Its potential lies in its superior in vitro and in vivo neutralizing capacity compared to palivizumab. 

• HNK20 is an IgA class recombinant antibody currently showing efficacy in animal models such as mice and rhesus monkeys. 

Other antibodies in preclinical research include: Anti-N-hRSV antibodies, 131–2 G, 3D3, and 2B11.