Toxic Exposures
Infant RSV Shots May Cause RSV, Other Infections or Death in Some Babies, Study Finds
French scientist Hélène Banoun, Ph.D., author of the preprint study that analyzed outcomes from the 2023-2024 RSV immunization campaign in four countries, found a “significant increase in mortality” among newborns between 2 and 6 days of age in France. Banoun’s findings suggest that antibody-dependant enhancement may be to blame.
The results from the first immunization campaign for nirsevimab, the monoclonal antibody shot approved to protect infants from RSV-related illness, raise questions about mass infant vaccination with the drug, according to a new preprint study.
The study by French scientist Hélène Banoun, Ph.D., which analyzed outcomes from the 2023-2024 respiratory syncytial virus (RSV) immunization campaign in the U.S., France, Spain and Luxembourg, contradicts some claims of success by U.S. public health agencies and medical associations.
In France in particular, Banoun told The Defender, “a significant increase in mortality among newborns between 2 and 6 days of age was observed from the start of the campaign: babies were injected before leaving the maternity ward.”
Deaths from nirsevimab also have been identified elsewhere. In clinical trials for the drug, 12 infants died. However, a spokesperson for the U.S. Food and Drug Administration (FDA) told CNBC when the drug was approved that “none of the deaths appeared to be related to nirsevimab.”
Yet according to Banoun’s study, both the FDA and the European Medicines Agency (EMA) noted a slightly higher death rate in treated groups in clinical trials of the drug, although the number of deaths was low.
Earlier this week, The Defender reported that documents obtained through a Freedom of Information Act from the Centers for Disease Control and Prevention (CDC) showed at least two infant deaths reported to the Vaccine Adverse Event Reporting System (VAERS) were linked to Beyfortus, the brand name for nirsevimab.
Regarding the increase in mortality, Banoun told The Defender, “All this was to be expected, and was undoubtedly due to the antibody-dependent-enhancement, or ADE, known to affect RSV antibodies, particularly those directed against the RSV F surface protein,” the viral protein targeted by RSV drugs.
ADE occurs when antibodies bind to a pathogen but can’t prevent infection. Instead, the antibodies do the opposite of what was intended — they act as a “trojan horse,” facilitating the pathogen’s entry into cells and exacerbating the immune response, according to the Children’s Hospital of Philadelphia.
According to Banoun, even though it was known that ADE could be a problem, the drug companies “incompletely assessed” the potential in their nirsevimab preclinical trials.
She stressed that ADE needs further study, but said it could explain why the all-cause hospitalization rate didn’t decrease in treated groups. Monoclonal antibodies can bind to a key receptor in infant cells and have the effect of increasing RSV infections like bronchiolitis.
ADE from monoclonal antibodies also can promote other infections. They also lead to immunosuppression, have an inflammatory effect in the lungs and cause thrombotic pneumonia, all of which could drive up hospitalization numbers.
Banoun’s analysis couldn’t draw conclusions about the drug’s efficacy in the U.S. campaign because coverage rates were only about 20%. In the three European countries, where coverage exceeded 80%, the drug did appear to be effective in reducing hospitalizations for RSV itself, Banoun found.
She also said that observational studies, like the one published today in the New England Journal of Medicine on the French campaign consistently exclude babies hospitalized for RSV illness within seven days of their shot.
But those illnesses may be due to ADE from the shot. So while that study reported similar efficacy findings to Banoun’s, it doesn’t account for some potential serious safety issues.
However, there was no reduction in the overall number of infants admitted to the hospitals and clinical trials similarly showed no reduction in hospitalizations.
Additionally, Banoun reported, in some cases, nirsevimab — marketed by Sanofi and AstraZeneca as Beyfortus — was also found to aggravate or increase RSV infection. This was evident in both the observational data and the clinical trials.
Banoun’s paper is undergoing peer review at the International Journal of Molecular Sciences. Her work has no industry funding or conflicts of interest.
Is mass immunization with Beyfortus scientifically and economically justified?
Previous attempts to develop an RSV vaccine failed after vaccine-antibody-enhanced RSV disease resulted in infant deaths, according to Banoun’s paper.
This led to vaccines being replaced with the prophylactic use of monoclonal antibodies.
While vaccines stimulate the immune system to trigger an immune response, monoclonal antibodies are proteins cloned in a lab. Delivered as a shot, they act like antibodies, seeking out antigens in the body to destroy. This is similar to how a human’s own antibodies work.
In the four countries in Banoun’s study, two monoclonal antibody treatments designed to bind to the RSV F protein are approved for infants.
Palivizumab, sold under the brand name Synagis, a short-acting monoclonal that must be administered monthly, was approved by the FDA in 1998 and the EMA in 1999, according to Banoun. It typically is used for high-risk infants. In 20 years of use, no ADE has been observed in association with the drug.
Nirsevimab was designed to get around the problem that palivizumab is very short-acting. However, the changes made to the monoclonal antibody treatment to create nirsevimab — changes that made the antibody more likely to recognize and bind to the RSV F protein — also made it bind more strongly to the receptors on other cells.
The improved binding capacity greatly increased the half-life of the antibody. However, it also increased its capability to promote ADE, facilitate the virus’s entry into cells and worsen the disease, Banoun wrote.
ADE produced by RSV monoclonal antibodies could disrupt the overall response to infections generally and make them worse. It also could damage the lungs and lead to inflammation in the advanced stages of the disease.
Not only has ADE been a problem in previous attempts to develop an RSV vaccine, but it occurred with some other monoclonal antibodies.
The study provided an exhaustive 36-page review of the various mechanisms by which ADE may function, evidence and gaps in the efficacy and safety data in the clinical trials that may be an indication of ADE issues, and evidence of ADE from animal studies that support this theory.
Banoun’s review concluded that it is unknown if nirsevimab can induce ADE at low concentrations, and studies of the phenomenon have been incomplete. However, scientific literature and indications from clinical trials and animal trials point to this distinct possibility, she said.
Banoun called for more rigorous research, made particularly urgent from the results of the 2023-2024 campaign where the drug reduced RSV hospitalizations, but overall hospitalizations of the target group remained constant.
And, she added, long-term follow-up of treated children is also needed to understand whether it is affecting them in the long term, even if the drug protects them against RSV in the short term.
The study closes with an economic cost-benefit analysis of the drug, set at 401.80 euros in France and $495 in the U.S. in 2023, increasing to $519.75 in 2024.
Existing cost-benefit analyses have shown that given waning immunity — babies are protected for only up to six months — and the evidence of the emergence of nirsevimab-resistant RSV strains, immunization is cost-effective only when given exclusively to at-risk infants.
She also noted that given the purpose of the immunization campaign is to reduce hospitalization, the cost-effectiveness of the mass campaigns is questionable.
“Is it therefore scientifically and economically reasonable to continue recommending immunization of all infants and young children for the following seasons?” Banoun asked. “Shouldn’t this expensive product be reserved for those at risk?”
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2023-2024 vaccination campaigns
RSV is a common respiratory virus that usually causes mild cold-like symptoms but can lead to hospitalization and, in rare cases, death in infants and the elderly.
By age 2, 97% of all babies have been infected with RSV, which confers partial immunity, making subsequent episodes less severe.
According to the CDC’s RSV webpage, approximately 58,000 to 80,000 children younger than age 5 are hospitalized due to RSV infection annually and 100 to 300 deaths occur annually in that group.
Different CDC data from 2021 showed that over 12 years, on average only 25 babies up to age 1 die annually in the U.S. from RSV.
Worldwide it is estimated that 33 million cases of RSV-associated acute respiratory infection occur each year in children under age 5 and hospitalization is required in 3% of the cases, Banoun wrote.
The EMA fast-tracked the approval of nirsevimab — aiming to reduce infant hospitalizations from RSV — and approved it on Oct. 31, 2022.
European countries have slightly different recommendations but generally the drug is recommended for infants and children under age 2.
The FDA approved nirsevimab in July 2023 and the CDC recommended it in August 2023.
The CDC recommends one dose of nirsevimab for infants younger than 8 months and born shortly before or who are entering their first RSV season if their mother didn’t receive the RSV maternal vaccine during pregnancy at least two weeks before the infant’s birth, or if her immunization status is unknown.
The CDC also recommends nirsevimab for infants and children ages 8-19 months at higher risk of severe RSV disease.
The four countries launched a campaign for mass vaccination of infants during the 2023-2024 RSV season.
The Biden administration rushed to work with Sanofi and AstraZeneca to make hundreds of thousands of doses of the antibodies available and has met with drugmakers to ensure more doses are available for next season.
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