New Paper Shows RSV Shot for Infants May Worsen Infection

Nirsevimab, a monoclonal antibody, may cause more severe RSV infection and death in some infants due to a mechanism that enhances the virus’ ability to infect cells.

By Megan Redshaw

A recently approved shot to prevent Respiratory Syncytial Virus (RSV) in infants may actually worsen the very infection it’s supposed to prevent. According to a new peer-reviewed paper published in Current Issues in Molecular Biology by independent researcher Hélène Banoun, nirsevimab—sold as Beyfortus—could trigger antibody-dependent enhancement (ADE), a phenomenon where antibodies, instead of neutralizing a virus, enhance its ability to infect cells, leading to more severe disease.

Nirsevimab, a monoclonal antibody produced by AstraZeneca and marketed by Sanofi, was approved by the U.S. Food and Drug Administration in July 2023 for preventing RSV in newborns and infants entering their first RSV season, marking the first time synthetic antibodies have ever been injected into infants on their first day of life.

“All mothers should read my article before accepting the Beyfortus they will be offered at the maternity hospital for their newborn,” Banoun, with the French Institute of Health and Medical Research, told Reform Pharma. 

While clinical trials initially showed that nirsevimab reduced hospitalizations, closer analysis raises serious concerns about the safety and efficacy of the shot. Clinical trial data show that in some cases, children who received the treatment experienced more severe outcomes, including deaths, compared to placebo groups. A significant number of participants were excluded from the final analysis, further calling into question the reliability of the safety data.

Data Show RSV Shot May Lead to More Severe Infections

According to the review, the Phase 1b/2a trial on preterm infants raises red flags. Of the 69 infants who received nirsevimab, five developed lower respiratory tract infections (LRTIs), and three had febrile convulsions—none of which occurred in the placebo group. Additionally, more children in the treated group developed LRTIs than in the placebo group, with one requiring hospitalization. Shockingly, 14.1% of treated children developed respiratory infections compared to 5.6% in the placebo group, suggesting that nirsevimab isn’t as effective as claimed and could lead to more severe infections.

An open-label study involving over 8,000 infants also showed that while "grade 3 serious adverse events" occurred at the same rate in treated and placebo groups, infections in the treated group were more severe. This raises further doubts about the drug's efficacy and safety, particularly in newborns.

Of the children treated with nirsevimab, only 500 out of 4,037 (12%) were less than seven days old, even though the shot is recommended for newborns. Additionally, 0.22% of the treated children were withdrawn from the study, though the reasons for these withdrawals were not specified. Moreover, RSV PCR tests were not routinely performed; they were only performed after hospitalization, and 16 of the hospitalized children did not undergo an RSV PCR test at all.

More Deaths in Infants Who Received RSV Jab 

The review also showed an imbalance in deaths between the nirsevimab-treated group and the control group. Twelve deaths occurred among the 3,710 treated participants (0.32%) compared to four deaths in the 1,797 control participants (0.22%). While these numbers are small, the discrepancy is concerning, especially since deaths after the study's end in the treated group were not fully reported. This raises significant safety questions, particularly for preterm infants.

In another study focused on preterm and medically fragile infants, five out of six deaths occurred in the nirsevimab group, and all were linked to pneumonia or bronchiolitis, suggesting the possibility that the drug may worsen these conditions.

These findings indicate that nirsevimab may be less effective and potentially more dangerous than its predecessor, palivizumab. Notably, RSV testing was not routinely performed, and no autopsies were conducted, leaving important questions about the role of immunopathological reactions, such as ADE, unanswered. With a notable percentage of treated children withdrawn from the study, it remains impossible to rule out ADE as a contributing factor to these deaths. 

The EudraVigilance database, which tracks adverse events for nirsevimab in Europe, recorded 140 reports as of April 15, 2024, primarily from healthcare professionals. Of these, 89 were related to "bronchiolitis," 129 were linked to "RSV," and 56 involved reports of the drug being ineffective. 

Only 26 reports concerned non-respiratory events. Bronchiolitis was the most frequently reported issue, which raises the possibility that these cases could be tied to ADE. Additionally, the Île de France pharmacovigilance center has indicated a theoretical risk that RSV infection could be worsened by non-neutralizing antibodies, which might explain the increased reports of bronchiolitis.

Alarmingly, several countries, including France, observed significant peaks in neonatal deaths during mass vaccination campaigns with nirsevimab. In France, deaths among infants aged two to six days surged in September and October 2023, coinciding with the vaccine rollout. Although mortality dipped in November, it rose again in December and January, aligning with continued immunization efforts. Similar trends were seen in the U.S., Luxembourg, and Spain, with increased hospitalizations for RSV and respiratory illnesses among vaccinated infants, further fueling concerns that the vaccine might exacerbate, rather than prevent, infections.

Nirsevimab-Induced ADE Can Worsen RSV

In the U.S., nirsevimab “immunization” coverage for children under 20 months of age was about 20% as of Oct. 1, 2023, with the CDC claiming a 90% effectiveness rate in preventing RSV-related hospitalizations. However, it’s unclear how the CDC calculated this percentage, and significant issues undermine its claim.

The study excluded hospitalizations occurring within seven days of vaccination, resulting in the omission of 20 children, which would have dramatically reduced the claimed effectiveness. Worryingly, 77% of RSV hospitalizations occurred within the first week after injection, raising suspicions of ADE.

According to Banoun, nirsevimab’s interaction with the neonatal Fc receptor (FcRn)—which helps extend the lifespan of antibodies—could be working against its intended protective effects. Rather than neutralizing the virus, FcRn may allow it to infect cells more easily, particularly in the lungs, leading to more severe respiratory infections. These concerns, combined with gaps in clinical data, suggest that nirsevimab may carry risks that were not fully explored before approval.

In other words, even though newborns have antibodies passed from their mothers, these antibodies don’t always protect them from severe RSV infections. In fact, babies with maternal RSV antibodies sometimes get sicker than those without. This could be due to the virus’s ability to escape the antibodies or the body's inflammatory response to infection.

While breastfeeding seems to lower the severity of RSV infections, maternal antibodies decrease significantly after two months, reaching their lowest point around six months—coinciding with the highest rates of hospitalizations for RSV. These antibodies also don’t stop reinfection, partly because they don't last long, and the virus can mutate. In some severe cases, like those linked to earlier RSV vaccines, the immune system's overreaction can cause severe lung inflammation, further complicating the infection.

In conclusion, while nirsevimab was touted as a breakthrough in RSV prevention, mounting evidence points to potential dangers, including more severe infections and even death. The drug’s association with ADE, along with the alarming spikes in neonatal mortality during vaccine campaigns, calls for a thorough re-evaluation of its safety and effectiveness.