Immunocompromised adults have a weaker response to RSV vaccines

Johns Hopkins Medicine researchers have shown that people 60 and older with weakened immunity -? especially organ transplant recipients who take immunosuppressive drugs 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 group with normal immune function.

The study, conducted by a research team at the Johns Hopkins Transplant Research Center, was published today in Journal of the American Medical Association (GLASS). 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 respiratory tract infections. It occurs most often in infants and young children, but is a threat to all age groups and can lead to more serious respiratory illnesses, such as pneumonia, in the elderly and immunocompromised.

We found that on average, the elderly who are immunocompromised developed fewer antibodies to RSV after vaccination compared to the very strong responses for healthy people over 60 years of age seen in the clinical trials used to validate the vaccines. In addition, antibody levels in immunocompromised individuals were highly variable, with some study participants showing strong increases in immunity due to the vaccines, while others barely responded at all.”

Andrew Karaba, MD, Ph.D., lead author of the study, Assistant Professor of Medicine, Johns Hopkins University School of Medicine

The researchers used an ongoing national study of Johns Hopkins Medicine -. emerging pathogens of concern in immunocompromised individuals (EPOC) -; to follow 38 people (between 64 and 72 years of age) who self-reported being 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 men and women, with 82% being solid organ transplant recipients and 74% taking two or more immunosuppressive drugs.

The two vaccines stimulate the immune system to target a critical protein on the surface of RSV, the F protein, in its pre-infection form, known as F pre-fusion. and prevent RSV from entering cells, contribute significantly to the prevention of RSV infections. Although most people are infected with RSV several times in their lives, natural infections do not lead to a sufficient level of virus-neutralizing, anti-fusion F antibodies to prevent reinfection and perhaps prevent serious disease.

Both RSV vaccines were designed to solve this drawback, and in fact, have been shown to successfully produce large amounts of pre-fusion F antibodies in trials with healthy adults. Why then, its editors GLASS the study asked, do immune responses to vaccines differ 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 variation in immunity, so we looked at it,” says senior study author William Werbel, MD, 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 the study participants who received Arexvy and those who received Abrysvo, we found that the group that received the adjuvant vaccine tended to have higher levels of RSV-neutralizing, anti-fusion F antibodies,” says Werbel. . “Thus, adjuvanted vaccines as a means of improving the immune response in immunocompromised individuals warrant further investigation in larger, more comprehensive studies.”

However, both Karaba and Werbel point out that this study does not suggest that RSV vaccines will not reduce RSV disease in immunosuppressed people.

The US Centers for Disease Control and Prevention (CDC) currently recommends that everyone 75 and older receive a single dose of RSV vaccine, as well as people 60 and older in high-risk groups for infection with 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 selection of vaccines for immunocompromised individuals,” 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, MD; Isabella Sengsouk? and Aaron Tobian, MD, Ph.D. Study co-author from New York University Grossman School of Medicine is Dorry Segev, MD, Ph.D., formerly of 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 Post-Transplant Protection COVID-19 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 fees and speaker fees from AstraZeneca, CareDx, Houston Methodist, Northwell Health, Optum Health Education, Sanofi, and WebMD.