Global analysis of more than 60,000 RSV viral sequences reveals that resistance to monoclonal antibodies remains rare.
RT’s Three Key Takeaways:
- Low Resistance Levels: An analysis of more than 60,000 viral sequences found that mutations linked to resistance against current respiratory syncytial virus prevention tools appear in less than 1% of circulating strains.
- Sustained Treatment Protection: The findings indicate that preventive monoclonal antibodies, including nirsevimab and clesirovimab, continue to safeguard infants against severe respiratory infections without evidence of sustained resistance spread.
- Enhanced Viral Surveillance: Researchers incorporated mutation libraries into an open-access platform to enable real-time tracking of viral evolution and help healthcare professionals monitor potential future resistance.
An analysis of more than 60,000 respiratory syncytial virus (RSV) sequences from around the globe revealed that viral variants associated with resistance to existing RSV prevention methods remain rare, according to a study published in Nature.
According to researchers from Fred Hutch Cancer Center, the findings support the continued clinical value of preventive antibodies and vaccines designed to shield infants and vulnerable patient populations from severe RSV illness, while offering valuable data to inform future preventive strategies.
Current RSV prevention strategies include monoclonal antibodies for infants and vaccines for older adults, which reduce disease severity and prevent hospitalization when administered prior to exposure. In addition, vaccines administered during the third trimester of pregnancy transfer protective antibodies to the fetus that persist after birth. Infants, immunocompromised patients, and older adults with weakened immune systems face heightened vulnerability to severe lower respiratory tract disease.
“It’s so incredible as a pediatrician, and as a mom, that we now have these prevention tools for RSV,” said Cassandra Simonich, MD, PhD, a research associate at Fred Hutch Cancer Center and a pediatric infectious diseases physician at Seattle Children’s. “We know these tools work really well in reducing severe RSV infections in babies. We want to ensure that these tools stay effective, and this study is a step toward ensuring our prevention methods keep working.”
Deep Mutational Scanning Evaluates Viral Evolution
Historically, researchers identified antibody resistance by passaging active viruses alongside antibodies in laboratory settings. In this study, investigators utilized a laboratory approach known as deep mutational scanning to build an expansive library of potential RSV mutations that could diminish the efficacy of preventive therapies.
“In the past, scientists have mostly identified RSV antibody resistance mutations by passaging the actual virus in the lab in the presence of antibodies,” said Jesse Bloom, PhD, an evolutionary virologist and professor at Fred Hutch Cancer Center. “With new techniques like the one in this paper, we can systematically characterize the effects of mutations to the key viral protein outside the context of actual pathogenic virus. We can then combine these measurements with biophysical modeling of antibody escape and analysis of natural viral sequences to understand the extent to which evolution might impact the effectiveness of these important antibodies.”
The investigative team reviewed 60,000 public RSV sequences spanning global cases and encompassing both RSV A and RSV B subtypes, which frequently co-circulate during respiratory illness seasons. Using deep mutational scanning, they systematically evaluated how thousands of mutations across the RSV fusion protein influenced antibody neutralization, scoring sequences for escape capability.
Monoclonal Antibodies Maintain Neutralization Capacity
Simonich estimated that fewer than 1% of circulating RSV sequences feature mutations linked to resistance, demonstrating that current infant immunizations remain robust.
“Our findings show that it was rare to find resistance to the RSV antibodies currently used for prevention,” said Simonich, in a news release. “So that’s encouraging for nirsevimab and clesirovimab because for both of these antibodies, it doesn’t seem like there’s any sort of sustained spread of resistance mutations.”
To aid ongoing tracking efforts across global healthcare networks, the investigators uploaded the mutation dataset into Nextstrain, an open-source pathogen surveillance platform. This integration allows researchers and clinicians to track RSV sequence data in real time and evaluate whether resistant strains increase in prevalence.
“The progress we’ve made in preventing severe RSV disease, especially among infants, has been remarkable,” said Simonich, in a news release. “We hope these findings will help researchers continue to improve prevention tools and maintain their effectiveness over the long term.”
The research was supported by the National Institutes of Health (NIH), and the Bill & Melinda Gates Foundation, with guidance from study coauthor Helen Y. Chu, MD, MPH, a professor of medicine at the University of Washington School of Medicine.
