People who are immunocompromised may not produce enough protective antibodies against RSV after vaccination

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Johns Hopkins Medicine researchers have shown that 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 vaccines against the respiratory syncytial virus (RSV) as people in the same age group with normal immune function. 

The study, conducted by a research team at the Johns Hopkins Transplant Research Center, was published today in the Journal of the American Medical Association (JAMA). It parallels earlier work done at the center to better understand how the immune systems of people who are immunocompromised respond to vaccines against SARS-CoV-2, the virus that causes COVID-19. 

RSV is a contagious pathogen that causes infections of the respiratory tract. It is most commonly seen in infants and young children, but poses a threat to all age groups and may lead to more serious respiratory illnesses, such as pneumonia, in the elderly and those who are 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,” says study lead author Andrew Karaba, M.D., Ph.D., assistant professor of medicine at the Johns Hopkins University School of Medicine. “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.” 

The researchers used an ongoing, Johns Hopkins Medicine-led national study — the Emerging Pathogens of Concern in Immunocompromised Persons (EPOC) — to follow 38 people (between ages 64 and 72) who self-reported that they are immunocompromised and received either the RSVPreF3-AS01 (also known as Arexvy) or RSVpreF (also known as Abrysvo) vaccine. The study group was evenly split between males and females, with 82% being solid organ transplant recipients and 74% taking two or more immunosuppressive medications. 

The two vaccines induce the immune system to target a critical protein on the surface of RSV, the F protein, in its pre-infection form, known as pre-fusion F. High levels of antibodies against pre-fusion F, particularly those that neutralize and block RSV from entering cells, are a major contributor in preventing RSV infections. Although most people are infected by RSV many times in their lives, natural infections do not lead to a sufficient level of virus-neutralizing, anti-pre-fusion F antibodies to prevent reinfections, and perhaps, prevent serious illness. 

Both RSV vaccines were designed to solve that shortcoming, and in fact, they have been shown to successfully generate large amounts of pre-fusion F antibodies in trials with healthy adults. So why, the authors of the JAMA study asked, do immune responses to the vaccines vary in people who are immunocompromised? 

“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, both Karaba and Werbel point out that this study does not suggest RSV vaccines will not reduce RSV disease in people who are immunocompromised. 

The U.S. Centers for Disease Control and Prevention (CDC) currently recommends that everyone 75 and older receive a single dose of an RSV vaccine, as well as people 60 or older in groups at high risk of infection by the virus — including people 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 other members of the research team from Johns Hopkins Medicine are Prasanthy Balasubramanian, Sc.M.; Camille Hage, M.D.; Isabella Sengsouk; and Aaron Tobian, M.D., Ph.D. The study co-author from the New York University Grossman School of Medicine is Dorry Segev, M.D., Ph.D., formerly with Johns Hopkins Medicine. 

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

Karaba reports receiving consulting fees from Hologic Inc. and 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. 

No other authors had disclosures to report.

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