Older Immunocompromised Folks May Need More From RSV Vaccines

Immune responses to respiratory syncytial virus (RSV) vaccines tended to fall short in older people with weakened immunity, a study found.

In 38 immunocompromised persons who received either the RSVPreF3-AS01E (RSVA-AS01E; Arexvy) or RSVpreF (Abrysvo) vaccine, preF IgG antibody titers rose a median 4.21-fold by 4 weeks — with 61% of the group meeting seroconversion, or criteria for immune response to RSV vaccination, reported William Werbel, MD, PhD, of the Johns Hopkins University School of Medicine in Baltimore, and colleagues.

“This study demonstrated heterogeneous antibody response to RSV vaccines among immunocompromised persons. In contrast to universal seroconversion and preF IgG fold rises greater than 10 in immunocompetent persons, approximately 40% of immunocompromised participants did not seroconvert or achieve a conservative neutralization threshold postvaccination,” according to the group’s research letter, published in JAMA.

The report also showed that preF and NT50 values were positively correlated. Overall, the NT50 rose from 395 at baseline to 2,978 at 4 weeks post-vaccine. The 19 study participants with high-titer neutralization and known vaccine type turned out to have received RSVPreF3-AS01E in four out of five cases.

“Better neutralization was seen among RSVA-AS01E recipients, suggesting possible augmentation by the vaccine adjuvant. Low antibody titers may indicate a role for additional vaccine doses to enhance immune response among immunocompromised persons,” Werbel and colleagues surmised.

CDC guidelines recommend a single dose of an RSV vaccine for people 75 and older, or people as young as 60 if they are immunocompromised or otherwise at high risk of RSV infection.

The adjuvanted RSV prefusion F protein-based vaccine RSVPreF3-AS01E Arexvy was first FDA approved for older adults in May 2023, followed by the approval of the unadjuvanted, bivalent RSV prefusion F protein vaccine Abrysvo a month later.

“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,” according to a statement by 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.”

The present study was based on the Emerging Pathogens of Concern in Immunocompromised Persons prospective cohort. Included were 38 adults age 64-72 with self-reported immunocompromising conditions who also reported RSV vaccination. They had to have paired baseline and 4-week post-vaccination samples and no receipt of immunoglobulin products after RSV vaccination.

Median age was 66 years, with 50% of the cohort being women. The group largely comprised organ transplant recipients on immunosuppressive medications (82%). Three-quarters were taking at least two immunosuppressive medications.

Study authors reported that preF IgG antibody titers rose from 87,292 AU/mL at baseline to 626,280 AU/mL at 2 weeks, 439,086 AU/mL at 4 weeks, and 464,170 AU/mL at 12 weeks.

Median 4-week NT50 fold rise was 6.97 and 58% achieved high-titer neutralization.

“Study limitations include the small convenience sample, absence of cellular data, and lack of correlations with vaccine effectiveness,” Werbel’s group acknowledged.

Also on the market, the mRNA-1345 RSV vaccine mRESVIA was not covered in the present report.