Johns Hopkins Medicine researchers have shown that people 60 years of age and older with weakened immunity (mainly organ transplant recipients who take immunosuppressive medications to reduce the risk of rejection and other people with immune system disorders) do not respond as strongly to vaccines against respiratory syncytial. virus (RSV) than 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 the journal Journal of the American Medical Association (JAM). It parallels previous work done 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 tract infections. It is most commonly seen in infants and young children, but poses a threat to all age groups and can cause more severe respiratory illnesses, such as pneumonia, in the elderly and those who are immunocompromised.
“We found that, on average, immunocompromised older adults developed fewer antibodies to RSV after vaccination compared to the very strong responses of healthy people over 60 years of age observed in clinical trials used to validate the vaccines,” says the lead author of the study, Andrew Karaba. , M.D., Ph.D., assistant professor of medicine at Johns Hopkins University School of Medicine. “In addition, antibody levels in immunocompromised people were highly variable: some study participants showed strong increases in immunity due to the vaccines, while others barely responded.”
Researchers used an ongoing national study led by Johns Hopkins Medicine, Emerging Pathogens of Concern in Immunocompromised People (COPD), to follow 38 people (ages 64 to 72) who reported they were immunocompromised and received either the vaccine. RSVPreF3-AS01 (aka Arexvy) or RSVpreF (aka Abrysvo). The study group was evenly divided between men and women: 82% were solid organ transplant recipients and 74% were taking two or more immunosuppressive medications.
The two vaccines induce the immune system to attack a critical protein on the surface of RSV, the F protein, in its pre-infection form, known as prefusion F. High levels of prefusion anti-F antibodies, particularly those that neutralize and block RSV entry into cells, contribute significantly to the prevention of RSV infections. Although most people become infected with RSV many times in their lives, natural infections do not lead to a sufficient level of virus-neutralizing anti-prefusion F antibodies to prevent reinfection and perhaps prevent serious illness.
Both RSV vaccines were designed to address that deficiency and, in fact, have been shown to successfully generate large amounts of prefusion F antibodies in trials with healthy adults. So why do the authors of the JAM The study asked: Do immune responses to vaccines vary in immunocompromised people?
“We suspected that a fundamental difference between the two vaccines (the presence or absence of an immune-stimulating chemical called adjuvant) might play a role in varying immunity, so we looked at that,” says the study’s lead author, William Werbel, M.D., Ph.D., assistant professor of medicine at Johns Hopkins University School of Medicine.
Arexvy contains an adjuvant while Abrysvo does not.
“When we compared antibody responses between study participants who received Arexvy with those who received Abrysvo, we found that the group that received the adjuvanted vaccine tended to have higher levels of anti-prefusion F antibodies that neutralize RSV,” he says Werbel. . “Therefore, adjuvant-enhanced vaccines as a means to improve the immune response in immunocompromised people deserve further investigation in larger and more comprehensive studies.”
However, both Karaba and Werbel point out that this study does not suggest that RSV vaccines do not reduce RSV disease in immunocompromised people.
The U.S. Centers for Disease Control and Prevention (CDC) currently recommends that everyone age 75 and older receive a single dose of RSV vaccine, as well as people age 60 and older in groups at high risk of infection with the virus, including people who are immunocompromised.
“As in 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 responses to the RSV vaccine that will provide guidance to optimize vaccine timing and selection for immunocompromised individuals,” Karaba says.
Along with Karaba and Werbel, the other members of the Johns Hopkins Medicine research team are Prasanthy Balasubramanian, Sc.M.; Camille Hage, MD; Isabella Sengsouk; and Aaron Tobian, M.D., Ph.D. The study’s co-author from New York University Grossman School of Medicine is Dorry Segev, M.D., 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 COVID Post-Transplant Protection Data Coordinating Center, Virginia Mason Medical Center Benaroya Research Institute Immune Tolerance Network.
Karaba reports receiving consulting fees from Hologic Inc. and speaking fees from PRIME Education. Werbel reports receiving consulting fees from 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 honoraria and speaker fees from AstraZeneca, CareDx, Houston Methodist, Northwell Health, Optum Health Education, Sanofi, and WebMD.