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RSV Vaccine Pipeline
A Snapshot of the RSV Vaccine Pipeline

Released: March 27, 2023

Angela Branche
Angela Branche, MD, FIDSA
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Key Takeaways
  • For older adults, several RSV vaccines are under investigation, with many completing or having recently completed phase III clinical trials.
  • Some younger adults are also at risk for severe RSV disease, such as those with underlying cardiopulmonary comorbidities and immunocompromising conditions; more data are needed to determine if RSV vaccines will be effective in these specific populations.  

Respiratory syncytial virus (RSV) disease burden in older adults is substantial. In fact, most RSV-related deaths in the United States occur in older adults. For these reasons, it is clear we need ways to prevent disease in this population, just like we try to prevent influenza.

Research and development for RSV vaccines started in the 1960s and was largely unsuccessful after a formalin-inactivated vaccine was found to cause worse disease after vaccination in infants.

Research into the development of RSV vaccines largely stalled thereafter until the 21st century and was boosted by isolation of the fusion glycoprotein (F protein) and a better understanding of its configurations (prefusion [preF] and postfusion [postF] forms). The preF form was found to stimulate a strong immune response and elicit antibodies that then could neutralize the virus or stop it in its tracks, preventing it from infecting cells and making more copies of itself. The ability to stabilize the F protein in its preF form helped relaunch RSV vaccine development and allowed us to develop effective candidate vaccines.

Vaccines in the Pipeline

Three types of RSV vaccines are under investigation in phase III trials. First, we have viral vector vaccines that use a carrier to deliver the RSV F protein, such as the Ad26.RSV.preF and MVA-BN RSV vaccines. Then we have protein subunit vaccines, another type where a stabilized preF version of the F protein is used to stimulate immune responses; examples include the RSVpreF and RSVPreF3-AS01E vaccines. Finally, we have mRNA-based vaccines (eg, mRNA-1345), which contain the mRNA code to make the stabilized preF protein in our own cells.

Phase III studies have been completed for 2 RSV vaccines in older adults: RSVpreF (RENOIR), and RSVPreFOAE (AReSVI-006). Each has demonstrated efficacy in preventing lower respiratory tract disease (eg, pneumonia and bronchitis) in more than 80% of study participants. Several other RSV vaccines are undergoing phase III studies (eg, Ad26.RSV.preF, mRNA-1345, MVA-BN RSV), with recent news earlier this year that the mRNA-1345 vaccine met primary efficacy endpoints in ConquerRSV, a randomized, placebo-controlled phase III study; similar efficacy against pneumonia and bronchitis resulted as the other 2 RSV vaccines that completed their phase III studies.

Of interest, many of these trials were conducted at the height of the COVID-19 pandemic, when several mitigation strategies were in place, such as mask wearing, social distancing, and quarantining/isolating. During this time, we saw a drastic reduction in all respiratory viruses, including RSV, for at least 2 seasons. Even when mitigation strategies were reduced and RSV returned, we still had lower than usual rates of RSV, but efficacy of the RSV vaccine was still demonstrated in these studies.

Anticipated Approvals

In the United States, the Vaccines and Related Biological Products Advisory Committee (VRBPAC) met on February 28 and March 1 to vote on the first 2 RSV vaccines, RSVpreF and RSVPreF3-AS01E, respectively. Both vaccines were voted as safe and efficacious in preventing RSV diseases in adults aged 60 years or older and recommended for licensure to the FDA. Based on voting by the VRBPAC, I anticipate licensure for both vaccines will be granted by the end of 2023.

In the meantime, while we wait to hear back about licensure by the FDA, the CDC’s American College of Immunization Practices (ACIP) will assess the benefit to public health and cost-effectiveness of deploying these vaccines in the United States. They will consider the burden of RSV disease and will make a recommendation for how these vaccines should be used.

Vaccine Recommendations, Target Populations

I predict that ACIP will recommend vaccines in adults aged 60 years or older because that is who was studied in phase III clinical trials. But there are still several outstanding questions. Should the recommendation be universal for all adults aged 60 years or older, or at a different age threshold? We know the risk of RSV disease and complications increases as people age. Does a healthy 60-year-old adult really need to be vaccinated, or is it more the 60-year-old adult with underlying cardiopulmonary disease? These are questions that the ACIP will be weighing before they give more nuanced recommendations.

Although age is certainly one of the most important independent risk factors, it is not the only one. Younger adults who have underlying cardiopulmonary diseases are also at risk for poor outcomes with RSV infection. During the next few years, we have a lot of work to do to understand if these vaccines should be licensed in people younger than 60 years with these underlying medical conditions—people who may be at even higher risk than a healthy 60-year-old adult.

There are other populations for whom the vaccines have not yet been studied, such as patients with immunocompromising conditions. In some immunocompromising conditions, if one becomes infected with RSV and have lower respiratory tract disease, mortality can be as high as 60%. Research will be needed to examine if these vaccines will be effective for these patients, too.

Finally, another group we need to protect against RSV is young children. RSV is the leading cause of hospitalization for respiratory illnesses in children 2 years of age or younger. For those aged 6 months or younger, we need to immunize their mothers so that they can transfer antibodies to their infants. Further data are needed, but studies of pediatric and maternal RSV vaccines are underway.  

It is a very exciting time for those of us who study and treat patients with RSV because soon we will have tools to prevent what is often a debilitating and potentially life-threatening illness in some of our most vulnerable populations.

Your Thoughts?

Which patients would benefit the most from an RSV vaccine? Join the discussion by posting a comment.