Researchers have discovered that individuals aged 60 and above with compromised immune systems do not have as strong of a response to vaccines for the respiratory syncytial virus (RSV) compared to their peers with normal immune function.
Researchers at Johns Hopkins Medicine have found that individuals aged 60 and older with weakened immunity—especially organ transplant recipients on immunosuppressive drugs intended to prevent organ rejection, as well as others with immune system disorders—exhibit a weaker response to RSV vaccines compared to those in the same age bracket with healthy immune systems.
This research, carried out by a team from the Johns Hopkins Transplant Research Center, was published today in the Journal of the American Medical Association (JAMA). It builds on previous studies aiming to understand how the immune systems of immunocompromised individuals react to vaccines for SARS-CoV-2, the virus responsible for COVID-19.
RSV is a highly contagious virus that infects the respiratory system. While it predominantly affects infants and young children, it can pose serious risks to individuals of all ages, especially the elderly and those with compromised immune systems, leading to conditions like pneumonia.
According to Andrew Karaba, M.D., Ph.D., the lead author and assistant professor of medicine at the Johns Hopkins University School of Medicine, “We found that, on average, older adults who are immunocompromised produced fewer antibodies against RSV following vaccination compared to the strong responses observed in healthy individuals over 60 during clinical trials.” He added, “Additionally, antibody levels in those with weakened immunity varied greatly, with some participants showing significant improvements while others had minimal responses.”
The team followed 38 participants (ages 64 to 72) enrolled in an ongoing national study titled Emerging Pathogens of Concern in Immunocompromised Persons (EPOC). These participants self-identified as immunocompromised and received either the RSVPreF3-AS01 (Arexvy) or RSVpreF (Abrysvo) vaccine, with a participant group comprised of 50% males and females, 82% of whom were solid organ transplant recipients and 74% on multiple immunosuppressive medications.
The two vaccines stimulate the immune system to recognize a vital protein on RSV, known as the F protein, in its pre-infection state (pre-fusion F). High levels of antibodies targeting pre-fusion F, especially those that neutralize the virus and prevent its entry into cells, play a crucial role in avoiding RSV infections. Natural infections typically do not provide enough virus-neutralizing anti-pre-fusion F antibodies to prevent reinfection or serious illness.
Both RSV vaccines aim to address this gap, and indeed, they have been clinically proven to induce high levels of pre-fusion F antibodies in healthy adults. This raises the question for the authors of the JAMA study: why do immune responses differ among immunocompromised individuals?
“We hypothesized that a fundamental distinction between the two vaccines—the presence or absence of an immune-boosting component called an adjuvant—could influence immune responses, so we investigated this,” said study senior 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.
Werbel noted, “In comparing antibody responses between participants who received Arexvy and those who received Abrysvo, we found that the group that received the adjuvant vaccine generally had higher levels of RSV-neutralizing, anti-pre-fusion F antibodies. Thus, exploring adjuvant-enhanced vaccines to boost immune response among the immunocompromised warrants further research in larger studies.”
Nonetheless, both Karaba and Werbel emphasize that this study does not imply that RSV vaccines will be ineffective in reducing RSV disease among individuals with weakened immune systems.
The U.S. Centers for Disease Control and Prevention (CDC) currently recommends that everyone aged 75 and older receive a single dose of an RSV vaccine, along with individuals aged 60 or older in high-risk categories, including those who are immunocompromised.
“Similar to our previous research with COVID-19 vaccines—which led to the recommendation for immunocompromised individuals to receive additional doses for enhanced protection—we anticipate further investigation into RSV vaccine responses for guidance on the optimal timing and vaccine selection for those with weakened immunity,” stated Karaba.
Alongside Karaba and Werbel, additional team members from Johns Hopkins Medicine included Prasanthy Balasubramanian, Sc.M.; Camille Hage, M.D.; Isabella Sengsouk; and Aaron Tobian, M.D., Ph.D. The study also had a co-author from New York University Grossman School of Medicine, Dorry Segev, M.D., Ph.D., who previously worked at Johns Hopkins Medicine.
This research was financially supported by several National Institute of Allergy and Infectious Diseases grants and a subaward from the COVID Protection After Transplant Data Coordinating Center.
Karaba disclosed receiving consulting fees from Hologic Inc. and speaking fees from PRIME Education. Werbel reported receiving consulting fees from the CDC/Infectious Diseases Society of America and AstraZeneca, as well as advisory board fees from AstraZeneca and Novavax. Segev has received consulting fees from various pharmaceutical companies and speaker fees from several healthcare organizations.
