A “substantial proportion” of infants who received the monoclonal antibody shot nirsevimab, intended to prevent RSV, developed a shot-resistant strain of the illness, according to a French preprint study. The authors said the finding “highlights the need for extended genomic surveillance,” and the need to periodically reevaluate the efficacy of the monoclonal antibodies.

A “substantial proportion” of infants immunized against the RSV virus with the monoclonal antibody shot nirsevimab — marketed by Sanofi and AstraZeneca as Beyfortus — developed a nirsevimab-resistant strain of the illness, according to a French study.

Over 12.5% of infants with breakthrough cases of RSV following immunization had variants of the illness with “intermediate to high-level resistance” to nirsevimab, including new strains of the virus not seen previously.

“The emergence of RSV-resistance described by this paper is simply incredible,” Children’s Health Defense Senior Scientist Karl Jablonowski said. He added:

“Most studies that shed light on the emergence of pathogens resistant to prophylaxis are population-wide and after many years of their use. Examples include the pertussis vaccine, the pneumococcal vaccine and the meningitis vaccine.

“This paper appears to show, with a high degree of certainty, the genesis of resistance.”

The study, designed to monitor escape variants of the virus and published on The Lancet’s preprint server, was conducted by a team of researchers from hospitals and research institutions across France.

The preprint follows a peer-reviewed paper published in The Lancet earlier this year by some of the same authors showing escape variants among a smaller number of infants. However, that study concluded the emergence of mutated variants was rarer.

The RSV monoclonal antibody shots were approved by the European Union and the U.K. in November 2022 and by the U.S. Food and Drug Administration in July 2023.

In September 2023, France was one of the first countries to launch a national immunization campaign with nirsevimab for newborns.

Many countries, including the U.S., followed France’s lead. The Centers for Disease Control and Prevention (CDC) added the shots to the childhood immunization schedule, recommending that either pregnant mothers get vaccinated or newborns get the monoclonal antibody shot.

Findings confirm concerns raised during clinical trials

The researchers conducted a national observational study of 1,023 infants under age 1 from across France who developed RSV-related illnesses during the 2024-2025 RSV season.

They compared susceptibility to the virus among infants who received the shot and those who didn’t.

Nirsevimab works by binding to the RSV virus. It attaches to a specific protein on the virus — the fusion protein — and blocks the virus’s ability to enter and infect the cells.

The researchers sequenced the RSV genomes from children infected with the virus to determine whether there had been a genetic change in the virus that allowed it to infect the children despite having received the shot.

There are two subtypes of the RSV virus — A and B.

In the 2023-2024 season, most RSV cases in France were subtype A. In the most recent season, most were subtype B. This is significant because most RSV-resistant strains appear to occur within subtype B — a concern already raised during clinical trials and in post-marketing data.

Approximately half of the infants in the study had breakthrough infections — meaning they were treated with nirsevimab but got RSV anyway. About half of those infections were subtype A, and half were subtype B.

Almost all of the RSV-resistant strains occurred among children with subtype B (12.5%). Only 1% of the RSV-resistant strains occurred in children with subtype A.

The RSV-B resistance showed greater diversity than previously seen and occurred long after the shots were administered.

RSV-B resistance was also more common among infants born prematurely. One case involved a highly resistant form of the virus detected nearly a year after the child was immunized.

The researchers concluded that “RSV-B resistance to nirsevimab can emerge in real-world conditions, with greater diversity and complexity than was previously recognised.”

They said the finding “highlights the need for extended genomic surveillance,” and the need to periodically reevaluate the efficacy of the monoclonal antibodies because “ongoing selective pressure may drive viral adaptation.”

The findings also suggest the need for “personalised prophylactic approaches” that may include maternal vaccination along with the monoclonal antibodies, or the administration of multiple antibodies, the researchers said.

Dominance of RSV-B means situation ‘could become very worrying’

French scientist Hélène Banoun, Ph.D., who studies the RSV virus but was not involved in this paper, told The Defender the situation “could become very worrying” because subtype B has become the dominant strain of RSV in France.

“This could select for resistant mutants whose dangerousness is unknown,” she said.

Banoun said it was possible that the resistance that emerged in subtype B during the first RSV season could have given it a selective advantage over subtype A in the second season.

“The exact type of resistance that appeared in 2023-2024 and 2024-2025 should be carefully explored” to determine whether this was the case, she said.

None of the infants infected with RSV who hadn’t received the shot were infected with an RSV-resistant strain. The authors hypothesized that this indicates the nirsevimab-resistant strains aren’t being transmitted to other infants.

Jablonowski said this was highly unlikely, adding:

“RSV is an infectious virus that, by its nature, transmits from one person to another. It is biologically implausible that nirsevimab-resistant RSV transmits only to nirsevimab-treated infants, sparing the untreated infants.

“The most reasonable explanation we are left with is that we are observing the genesis of RSV-resistance in nirsevimab-treated infants.”

Lead authors have ties to Big Pharma

Sixty-seven of the infants in the study had mothers who were vaccinated against RSV, but none of those babies had the resistant strains.

“Though this would be a point in favor of maternal vaccinations over infant immunization, they both come with a mixed bag of adverse effects, leaving parents to balance the risks,” Jablonowski said.

The French Ministry of Health and Prevention and the French ANRS/Emerging Infectious Diseases funded the study.

According to the conflict of interest statement, the lead authors who designed the study have financial ties to major pharmaceutical companies, including Sanofi and AstraZeneca, which produce the shots.

The authors said the research “strongly supports the continued high efficacy of nirsevimab at the population level” because the mutations hadn’t been found in infants who hadn’t received the shot.

Banoun said, “The authors are all linked to the industry, so if they criticize Beyfortus, we can imagine that there really is a worrying problem.”

This article was originally published by The Defender — Children’s Health Defense’s News & Views Website under Creative Commons license CC BY-NC-ND 4.0. Please consider subscribing to The Defender or donating to Children’s Health Defense.