Race for RSV vaccine approval: URMC researchers lead the way

The US Food & Drug Administration (FDA) is currently reviewing two candidates for a vaccine to prevent respiratory syncytial virus (RSV) in the elderly. Researchers at the University of Rochester Medical Center (URMC) are helping to develop one of them – a vaccine developed by Pfizer that is detailed in a new study just published in the New England Journal of Medicine (NEJM). Of the four adult RSV vaccine candidates (two under review by the FDA and two with late-stage clinical trials), URMC participated in the study of three of them.

RSV in the elderly has become a growing concern. There are about 60,000 to 120,000 hospitalizations and 6,000 to 10,000 deaths in adults 65 or older each year due to RSV infection, according to the CDC. The severity of RSV disease may increase with age and comorbidities, such as chronic obstructive pulmonary disease, congestive heart failure, and asthma. Along with COVID and influenza, RSV has contributed to the “triple epidemic” that has strained the country’s health system in recent months.

Previous research has shown that RSV infection does not give a person long-lasting immunity afterwards, and reinfection can occur throughout life. There is currently no FDA-approved RSV vaccine, but after nearly five decades of vaccine development efforts, researchers are on the verge of approval.

Edward Walsh, MD, a professor of medicine, has a long history with Pfizer, working on several viral pathogens over the years. This long-standing relationship led to URMC being named the lead site with Walsh as the national principal investigator for Pfizer’s Phase 3 RSV vaccine clinical trial for the elderly. In late February, Pfizer presented the efficacy and safety data from this clinical trial, available in the NEJM article, to the FDA and the Vaccines and Related Biologicals Advisory Committee (VRBPAC). Walsh was also the principal investigator of the preliminary trials that preceded the phase 3 study.

Promising results show Pfizer’s vaccine is 66.7% effective in preventing general illnesses, 85.7% effective in preventing lower respiratory tract infections with three or more symptoms, and 62.1 effective % to prevent acute respiratory infections. After presenting comprehensive data, the VRBPAC voted to recommend this vaccine to the FDA for approval.

“RSV is the worst disease that no one knows about,” said the co-researcher Ann Falsey, MDco-director of UR Vaccine Processing and Evaluation Unit, part of the National Institute of Allergy and Infectious Diseases (NIAID) network that was instrumental in studying the first FDA-approved COVID vaccine. “It started getting a lot of press last year after activity increased when COVID public health measures were relaxed, but every year it consistently causes a significant number of hospitalizations and deaths. deaths in people aged 65 and over.

Falsey plays a leading role in RSV vaccine development at URMC. It recently published the results of a phase 2 clinical trial in a New England Journal of Medicine article on the safety and effectiveness of an alternative RSV vaccine for the elderly. At another FDA/VRBPAC meeting to review a vaccine candidate from GlaxoSmithKline (GSK), Falsey, although not involved in their clinical trials, came to the meeting as an expert, testifying to the burden of RSV on the community.

Walsh and Falsey have been leading vaccine researchers for decades. Walsh has been researching RSV since the 1980s, describing the epidemiology and clinical features of RSV in adults, with an emphasis on high-risk elderly populations. His early work was the first to identify and characterize the RSV(F) fusion protein, which is used in current vaccine candidates. Falsey has been involved in clinical and translational vaccine research in respiratory viral infections in adults, including RSV, influenza, COVID, parainfluenza, and human metapneumovirus. She is a permanent member of the Clinical Studies and Field Research Section and a member of the steering committees of the Global Influenza Initiative, the Infectious Diseases Society of America, and the American Virology Society.

Walsh and Falsey were at the forefront of FDA approval of COVID vaccine. They took the lessons of this period and applied them to the development of the RSV. “We could do bigger clinical trials faster,” Walsh said, “we knew how to get everyone on board.”

Like most current flu and COVID vaccines, this RSV vaccine does not contain live virus. Instead, it contains this fusion protein that “protrudes” from the surface of RSV and helps it fuse with host cells, as the name suggests. As a backup, this version of the vaccine also contains a small piece of viral DNA that tells cells how to make the RSV fusion protein. RSVpreF is a bivalent recombinant protein subunit vaccine that consists of equal amounts of stabilized prefusion F (preF) antigens from the two major RSV subgroups: RSV A and RSV B.

Unlike flu and COVID vaccines, which must be updated frequently to keep pace with mutating viruses, the Pfizer RSV vaccine candidate has broad immunity. The RSV fusion protein used in the vaccine can protect against many different strains of RSV. There are two forms of proteins that change shape before and after fusing with a cell. Previous clinical trials have shown that post-fusion-based vaccines were insufficient to produce a robust immune response and did not protect against RSV disease. Later trials showed that pre-fusion vaccines elicited stronger immune responses, so this current vaccine is based on the pre-fusion protein.

A decision from the FDA is expected in the coming months.