Two products to protect infants from respiratory syncytial virus (RSV) have the potential for federal approval in the coming months, but experts are continuing to grapple with unanswered questions and logistical hurdles.
The Centers for Disease Control and Prevention’s (CDC’s) Advisory Committee on Immunization Practices (ACIP) on Thursday discussed some of these outstanding issues regarding Pfizer’s RSVpreF vaccine for pregnant women and monoclonal antibody nirsevimab for infants and high-risk young children that was developed by AstraZeneca in partnership with Sanofi.
An FDA advisory committee voted in favor of RSVpreF in May, although several members were concerned about preterm births. Earlier this month, another FDA committee voted in favor of nirsevimab. The FDA could make decisions on both in the next few months, which would be followed by recommendations from ACIP, which did not vote on either RSV product Thursday.
RSV can cause severe lower respiratory tract disease such as bronchiolitis or pneumonia and is the leading cause of hospitalization in U.S. infants. There are about 58,000 to 80,000 hospitalizations and 100 to 300 deaths per year in children under 5 years, according to CDC data. No vaccines are licensed in the U.S. to prevent RSV in children. Another monoclonal antibody, palivizumab, is available only for certain high-risk infants and young children.
Clinical trial data show RSVpreF given to pregnant women is about 82% effective in preventing severe lower respiratory tract infection in infants at 3 months of age and 69% effective at 6 months. Effectiveness against medically attended infections of any severity was 57% at 3 months and 51% at 6 months.
Data on nirsevimab also are promising. In term and late preterm infants, efficacy was 74.9% against medically attended disease and 60.2% against hospitalization after five months, although the latter figure had broad confidence intervals that went below 0.
CDC officials said Thursday most infants likely would not need both products unless an infant is considered to have insufficient protection from the maternal vaccine or is at high risk of severe disease. They laid out the pros and cons of each product as well as preliminary clinical considerations.
The maternal vaccine may be more resilient to mutations, lower in price and provide protection at birth. However, the protection likely wanes more quickly than nirsevimab, according to the CDC. Some infants may not get full protection from maternal vaccination if they were born too soon after immunization, born prematurely or due to maternal disease. Maternal uptake of flu and tetanus, diphtheria and pertussis (Tdap) vaccines tends to be lower than routine childhood vaccines, and it’s unclear if pregnant people would accept multiple vaccines. There also are outstanding questions about whether RSVpreF would interfere with the effectiveness of Tdap if given together.
“There’s a very narrow window to give a bunch of vaccines to pregnant women,” said ACIP Chair Grace M. Lee, M.D., M.P.H., associate chief medical officer for practice innovation at Lucile Packard Children’s Hospital in Palo Alto, Calif. “Given that there are several on the table, what I would want to know is how to counsel them in terms of risk and benefit.”
Some ACIP members also are concerned about preterm births when pregnant women received RSVpreF. Clinical trials showed a preterm birth rate of 5.7% in the vaccine group compared to 4.7% in the placebo group. Pfizer representatives have said these differences were driven largely by data from South Africa and are not statistically significant. However, the CDC noted trials of a similar GSK maternal RSV vaccine were halted after finding an imbalance of preterm births.
“I don’t know that we have come to a sense of whether or not there is a biologically plausible mechanism, and I think our work group may remain conflicted on different hypotheses,” said Katherine Fleming-Dutra, M.D., FAAP, who works for the CDC’s National Center for Immunization and Respiratory Diseases and co-leads the ACIP’s RSV work group.
Nirsevimab could have the benefit of being given just as infants are entering RSV season. However, it has its own complications due to being characterized as a therapeutic, not a vaccine. This classification raises questions around insurance coverage and whether it would be included in the immunization schedule, immunization registries and Vaccines for Children program. It also would be monitored in a separate FDA safety system from vaccines, and some states would restrict which health care providers can administer it.
“When these monoclonal antibodies are considered therapeutics on a technical level, then that sends it down a pathway that makes it more complicated,” said Sarah Meyer, M.D., M.P.H., chief medical officer for the CDC’s Immunization Services Division. “… It’s those kinds of complications we acknowledge are going to be a barrier, and we are working very hard to try to mitigate them.”
If the CDC decides infants don’t need both products, determining whether an infant’s mother had been vaccinated may be an additional challenge in some settings.
ACIP is expected to continue to discuss both products when it meets in October and could vote on them if they have been approved by the FDA.
In other moves this week, the committee voted on changes to vaccines for pneumococcal disease and influenza. Visit https://publications.aap.org/aapnews/news/24881 for details.
- AAP policy Updated Guidance for Palivizumab Prophylaxis Among Infants and Young Children at Increased Risk of Hospitalization for Respiratory Syncytial Virus Infection
- Information from the AAP Red Book on RSV
- Information for clinicians from the CDC on RSV
- Information for parents from HealthyChildren.org on RSV symptoms and when to call a doctor