A pediatric vaccine for respiratory syncytial virus (RSV) is proving to be elusive, according to news from the U.S. Food and Drug Administration.
RSV is a highly contagious, common respiratory virus that infects the nose, throat, and lungs. And while it does not usually cause severe illness in healthy adults and children, some people with RSV infection, especially older adults and infants younger than 6 months of age, can become very sick and may need to be hospitalized.
But enrollment for all clinical studies of infant RSV vaccines is now on hold due to safety concerns, explained a Dec. 11 briefing document from the FDA that was released ahead of a meeting of the FDA's Vaccine and Related Biologic Products Advisory Committee (VRBPAC) last week.
The document notes that a phase 1 trial of two experimental Moderna RSV vaccines in infants aged five to eight months was paused in July. The pause came after five cases of severe to very severe lower RSV respiratory tract infections were reported among the 40 babies who received the vaccine dose, compared with just one case in the placebo group of 20. Five infants required hospitalization, with one needing mechanical ventilation.
It all “has uncertain implications for the ongoing and future pediatric development of other non-live attenuated [inactivated] RSV vaccines," said the FDA, which put a hold on the trial after the July incident.
For adults aged 60 and older, mRNA-1345, marketed under the brand name mRESVIA, was approved by the FDA in May for use in adults aged 60 and older. It's one of three RSV vaccines—including GSK’s Arexvy and Pfizer’s Abrysvo—that have been licensed for adults and pregnant women within the past 2 years (with maternal immunization providing protection for a baby’s first six months of life).
And while 2023 brought the development of a monoclonal antibody for infants, a type of passive immunization that provides short-term protection from RSV, there has yet to be an actual RSV vaccine for children—despite those under 5 being the most vulnerable population, with RSV being the leading cause of infant hospitalization in the United States.
But scientists have been proceeding with caution, as the July incident was not the first time development of a pediatric RSV vaccine has prompted safety concerns, noted the FDA document. In the 1960s, two infants died during an RSV vaccine trial, and 80% were hospitalized, after it caused vaccine-associated enhanced respiratory disease (VAERD).
That “cast a decades long shadow over RSV vaccine development,” David Kaslow, who heads FDA’s vaccine branch, said at the VRBPAC meeting.
Researchers are now hoping the Moderna trial situation does not get exploited by those pushing anti-vaccine agendas, including president-elect Donald Trump’s nominee to head the Department of Health and Human Services, Robert F. Kennedy Jr., “We want this vaccine field to move forward and this is a great thing for them to jump on and say, ‘Oh, this is so toxic, scary, we can’t do this,” Coleen Cunningham, a pediatrician at the University of California, Irvine, told Science. “I think that would be a mistake.”
While Moderna will continue to monitor trial participants and gather additional data, there are no plans to restart the trial in children younger than 2.
Some VRBPAC members said they remained hopeful that an RSV vaccine will be developed for infants, and that more information was needed. In the meantime, Michael R. Nelson, M.D., PhD., chief of the asthma, allergy, and immunology division at the University of Virginia School of Medicine, said at the meeting, "The system worked, the safety signal was reached, the proper pause was put in place."
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