RSV Vaccine Response in Immunocompromised Adults

According to Johns Hopkins Medicine researchers, people 60 years or older with weakened immunity, primarily organ transplant recipients who take immunosuppressive medications to reduce the risk of rejection, and others with immune system disorders, do not respond as strongly to respiratory syncytial virus (RSV) vaccines as people of the same age with normal immune function.

A team of researchers at the Johns Hopkins Transplant Research Center conducted the study, which was published today in the Journal of the American Medical Association (JAMA). It builds on previous research at the center to better understand how the immune systems of immunocompromised people respond to immunizations against SARS-CoV-2, the virus that causes COVID-19.

RSV is a contagious bacterium responsible for respiratory tract illnesses. It is most frequent in newborns and young children, although it affects people of all ages and can progress to more serious respiratory disorders like pneumonia in the elderly and the immunocompromised.

We found that on average, older adults who are immunocompromised developed fewer antibodies against RSV following vaccination as compared with the very strong responses for healthy people over age 60 seen in the clinical trials used to validate the vaccines. Additionally, antibody levels in people who are immunocompromised were highly variable, with some study participants showing strong increases in immunity because of the vaccines while others barely responded.”

Andrew Karaba, M.D., Ph.D., study lead author, assistant professor of medicine, Johns Hopkins University School of Medicine

The researchers used an ongoing national study led by Johns Hopkins Medicine, the Emerging Pathogens of Concern in Immunocompromised Persons (EPOC), to follow 38 people (aged 64 to 72) who self-reported being immunocompromised and received either the RSVPreF3-AS01 (also known as Arexvy) or the RSVpreF (also known as Abrysvo) vaccine. The study population was evenly split between men and women, with 82% receiving solid organ transplants and 74% using two or more immunosuppressive medicines.

The two vaccinations cause the immune system to target a crucial protein on the surface of RSV, known as pre-fusion F. High levels of antibodies against pre-fusion F, particularly those that neutralize and prevent RSV from entering cells, play a significant role in preventing RSV infections. Although most people are infected with RSV multiple times in their lives, natural infections do not produce a sufficient amount of virus-neutralizing, anti-pre-fusion F antibodies to avoid reinfections and, potentially, significant illness.

“We suspected that a fundamental difference in the two vaccines -;the presence or absence of an immune-stimulating chemical called an adjuvant -; might play a role in the variance in immunity, so we looked at that,” says study senior author William Werbel, M.D., Ph.D., assistant professor of medicine at the Johns Hopkins University School of Medicine.

Arexvy contains an adjuvant while Abrysvo does not.

“When we compared the antibody responses between those study participants who received Arexvy with those who got Abrysvo, we found that the group receiving the adjuvanted vaccine tended to have higher levels of RSV-neutralizing, anti-pre-fusion F antibodies,” says Werbel. “So, adjuvant-enhanced vaccines as a means of improving immune response in people who are immunocompromised merits further investigation in larger, more comprehensive studies.”

However, Karaba and Werbel emphasize that this study does not imply that RSV immunizations will not reduce RSV disease in immunocompromised individuals.

The US Centers for Disease Control and Prevention (CDC) currently advises that everyone 75 and over receive a single dose of an RSV vaccine, as well as persons 60 and older in groups at high risk of virus infection, such as those who are immunocompromised.

“As with our previous work with COVID-19 vaccines [which led to recommendation that people who are immunocompromised getting additional vaccine doses to improve protection], we look forward to additional research on RSV vaccine responses that will provide guidance for optimized timing and vaccine selection for people who are immunocompromised,” says Karaba.

Along with Karaba and Werbel, the Johns Hopkins Medicine research team includes Prasanthy Balasubramanian, Sc.M., Camille Hage, M.D., Isabella Sengsouk, and Aaron Tobian, M.D., Ph.D. Dorry Segev, M.D., Ph.D., formerly of Johns Hopkins Medicine, is a study co-author from New York University’s Grossman School of Medicine.

The work was supported by National Institute of Allergy and Infectious Diseases grants 3U01A11338897-04S1, K08A1156021, and K23A1157893, as well as subaward 3UM1AI109565 from the COVID Protection After Transplant Data Coordinating Center, Immune Tolerance Network at the Benaroya Research Institute at Virginia Mason Medical Center.

Karaba discloses getting consultancy money from Hologic Inc., as well as speaking fees from PRIME Education. Werbel reports receiving consulting fees from the CDC/Infectious Diseases Society of America and AstraZeneca; and advisory board fees from AstraZeneca and Novavax. Segev reports receiving consulting fees from AstraZeneca, CareDx, Moderna Therapeutics, Novavax, Regeneron and Springer Publishing; and speaker fees and honoraria from AstraZeneca, CareDx, Houston Methodist, Northwell Health, Optum Health Education, Sanofi and WebMD.