RSV Vaccine Breakthrough Examined at AAAS Meeting

Barney Graham at the AAAS annual meeting, 5 Mar. 2023 (A. Kotok)

5 Mar. 2023. As three vaccines against respiratory syncytial virus reach FDA review, a scientific conference explored a key breakthrough researchers achieved to get to this point. Immunologist Barney Graham, former deputy director of the Vaccine Research Center at National Institutes of Health, and now at Morehouse College medical school in Atlanta, described the journey today in a session of the American Association for Advancement of Science or AAAS annual meeting in Washington, D.C.

Respiratory syncytial virus or RSV is an enigmatic viral pathogen that affects people in all age groups from infants to older adults, where for all but the very young and very old, infections rare usually cause more than mild symptoms resembling the common cold. But for infants, older individuals, and people with chronic diseases, RSV can result in severe infections and symptoms. In severe cases, RSV can spread to the lower respiratory tract, causing inflammation in the airways from pneumonia or bronchiolitis. RSV is responsible for some 58,000 hospitalizations in children under the age of five years, and 14,000 annual deaths among people over the age of 65 in the U.S. Worldwide, some 64 million RSV cases each year lead to 160,000 deaths.

Graham noted that respiratory disease researchers have known for decades that antibodies can diminish the severity of RSV infections, but clinical trials of an early vaccine in the 1960s resulted in two patient deaths and limited effectiveness among more vulnerable patients. He pointed out that original antibodies bound to but did not neutralize the viruses. And T-cells generated by the early vaccine produced damaging inflammatory cytokine enzymes in the immune response.

Freeze protein target in pre-fusion state

Graham began working in 1985 to better understand the mysterious structure of RSV, which led to discovery of a key protein target on the viral surface known as protein F. In their research, Graham and colleagues at the Vaccine Research Center revealed that upon infection, the virus fuses with the cell and the F protein rearranges its structure, changing binding site targets from the protein’s pre-fusion state. The F protein’s pre-fusion state is critical for vaccine development, said Graham, since antibodies have much higher potency before the virus fuses with cells.

By 2013, the RSV team found they could freeze F proteins in their pre-fusion state before it changes its structure, presenting solid targets for vaccine developers. As a result, said Graham, new vaccine candidates produce antibodies with “10- to 20-fold more immediate potency” sustained with four- to five-fold more potency for at least a year. And by 2022, several drug makers reported successful clinical trials of RSV vaccine candidates for vulnerable populations, leading Science magazine, published by AAAS, to include Graham’s work with RSV among the finalists for breakthrough of the year in 2022.

Since the start of 2023, said Graham, the Food and Drug Administration accepted for final review or received advisory committee recommendations to begin review of three RSV candidate vaccines for vulnerable populations. In January, FDA agreed to review the biologics license for an RSV vaccine candidate for newborns and infants developed by drug makers AstraZeneca and Sanofi. And in just last week, an FDA advisory committees recommended approval of two RSV vaccines for older adults made by Pfizer and GSK, formerly GlaxoSmithKline, as well as a version of the Pfizer vaccine for pregnant women to protect infants.

Two other vaccine candidates, by Janssen, a division of Johnson & Johnson, and Moderna, are in late-stage clinical trials to protect older adults. Graham noted that Moderna’s vaccine is based on messenger RNA, like its Covid-19 vaccine.

More from Science & Enterprise:

• Clinical Trial Underway Testing Influenza Vaccine Patch
• Nasal Spray Vaccine Shown to Stop Gonorrhea Infections
• CEPI Assessing Advanced RNA Nanoparticle Vaccine
• Covid-19 Vaccine Patch Clinical Trial Begins
• RSV Nose Drops Vaccine Gets FDA Fast Track Tag

Disclosure: The author owns shares in Pfizer and Johnson & Johnson

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