Immunocompromised adults have a lower response to RSV vaccines

Scientists from Johns Hopkins Medicine have shown that people aged 60 and older with weakened immune systems -; primarily organ transplant recipients taking immunosuppressive drugs to reduce the risk of rejection and other people with immune system disorders -; do not respond as strongly to respiratory syncytial virus (RSV) vaccines 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 (). This is consistent with previous work at the center to better understand how the immune systems of immunocompromised people respond to vaccines against SARS-CoV-2, the virus that causes COVID-19.

RSV is a contagious pathogen that causes respiratory infections. It most often occurs in infants and young children, but it poses a risk to all age groups and can lead to more serious respiratory diseases, such as pneumonia, in older people and people with weakened immune systems.

We found that immunocompromised older adults, on average, developed fewer antibodies to RSV after vaccination, compared with the very strong responses in healthy people over 60 years of age observed in clinical trials used to validate vaccines. “In addition, antibody levels in immunocompromised people were highly variable, with some study participants showing a significant increase in immunity after vaccination, while others barely responded.”

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

The researchers used an ongoing national study led by Johns Hopkins Medicine: Emerging Pathogens of Concern in Immunocompromised Persons (EPOC) -; We followed 38 people (aged 64 to 72 years) who self-reported that they were immunocompromised and received the RSVPreF3-AS01 (also known as Arexvy) or RSVpreF (also known as Abrysvo) vaccine. The study group was equally divided into men and women, with 82% being solid organ transplant recipients and 74% taking two or more immunosuppressive drugs.

Both vaccines induce the immune system to attack a critical protein on the surface of the RSV virus, the F protein, in its pre-infection form, called pre-fusion F. High levels of prefusion F antibodies, especially those that neutralize and block RSV entry into cells, play a major role in preventing RSV infection. Although most people become infected with RSV multiple times in their lives, natural infections do not produce sufficient levels of virus-neutralizing anti-fusion F antibodies to prevent reinfection and possibly prevent serious disease.

Both RSV vaccines were developed to address this shortcoming and have been shown to be effective in generating large amounts of prefusion F antibodies in studies in healthy adults. So why, the study authors ask, is the immune response to vaccines different in immunocompromised people?

“We suspected that a fundamental difference between the two vaccines – the presence or absence of a chemical that stimulates the immune system called an adjuvant – might play a role in differences in immunity, so we looked into it,” says senior study author William Werbel, M.D., assistant professor of medicine at the School of Medicine Johns Hopkins University.

Arexvy contains an adjuvant, while Abrysvo does not.

“When we compared the antibody response of study participants who received the Arexvy vaccine to those who received Abrysvo, we found that the group receiving the adjuvanted vaccine had higher levels of RSV-neutralizing and prefusion-preventing F antibodies,” says Werbel. “Thus, adjuvanted vaccines as a way to improve the immune response in immunocompromised individuals deserve further investigation in larger, more comprehensive studies.”

However, both Karaba and Werbel note that this study does not suggest that RSV vaccines will not reduce RSV cases in immunocompromised people.

The U.S. Centers for Disease Control and Prevention (CDC) now recommends that all people age 75 and older receive a single dose of the RSV vaccine, as well as people age 60 and older who are at high risk for infection with the virus; including people with reduced immunity.

“Similar to 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 response that will provide guidance on optimized vaccine timing and selection for immunocompromised individuals,” Karaba says.

In addition to Karaba and Werbel, the other members of the Johns Hopkins Medicine research team are Prasanthy Balasubramanian, Sc.M.; Camille Hage, M.D.; Isabella Sengsouk; and Aaron Tobian, M.D., Ph.D. The co-author of the study from New York University’s Grossman School of Medicine is Dorry Segev, M.D., formerly of Johns Hopkins Medicine.

This work was supported by grants from the National Institute of Allergy and Infectious Diseases 3U01A11338897-04S1, K08A1156021, and K23A1157893; and supplemental award 3UM1AI109565 from the COVID Post-Transplant Protection Data Coordinating Center, Immune Tolerance Network at the Benaroya Research Institute at 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 Infectious Diseases Society of America CDC/Infectious Diseases Society 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.