Giving RSV and Flu Vaccines Together Led to Adequate Immune Responses

Administering the respiratory syncytial virus (RSV) prefusion F protein vaccine (Arexvy) at the same time as the adjuvanted seasonal quadrivalent influenza vaccine stimulated an adequate immune response and was safe in older adults, a phase III randomized trial showed.

Among adults ages 65 and older, co-administration of the RSV and influenza vaccines resulted in hemagglutination inhibition titers that were noninferior to those with sequential administration for three out of four influenza strains, as well as noninferior neutralization titers for the RSV-A and RSV-B subtypes, at 1 month after vaccination, reported Shady Kotb, PhD, of GSK in Wavre, Belgium, and colleagues in Clinical Infectious Diseases.

These vaccines can be co-administered in older adults “without clinically relevant interference with the immune responses to either vaccine and with a clinically acceptable safety and reactogenicity profile,” the authors wrote. “Given the seasonal overlap of these 2 infections, the ability to give both vaccines during a single doctor’s visit may improve convenience and increase uptake of both vaccines, ultimately reducing the high burden of both influenza and RSV disease among older adults.”

Titers were considered noninferior if the upper limit of the two-sided 95% confidence intervals (CIs) for the adjusted geometric mean titer (GMT) ratios was ≤1.50.

Immunogenicity with co-administration was noninferior for influenza strains A/Victoria(H1N1), B/Victoria, and B/Yamagata. However, noninferiority criteria were “marginally missed” for the A/Darwin(H3N2) influenza strain (95% CI upper limit 1.53), Kotb and team noted.

The low hemagglutination titers for H3N2 may have been due to rapid mutation of that strain, which might blunt the immune response, the authors said. Alternatively, the hemagglutination assay may have not accurately detected a response.

In a post-hoc analysis using a different type of assay (microneutralization), the researchers did observe higher titers for H3N2 than those observed with the hemagglutination inhibition assay at 1 month post-vaccination. Based on the microneutralization assay, responses for H3N2 were similar in the co-administration and sequential administration groups, “supporting an adequate immune response to the A/Darwin(H3N2) vaccine strain after co-administration,” Kotb and colleagues wrote.

With the microneutralization assay, the post-vaccination adjusted GMT ratio was 1.23 (95% CI 1.06-1.42), meeting the noninferiority criteria.

Seroconversion rates for hemagglutinin antibodies 1 month after co-administration for each influenza vaccine strain also met noninferiority criteria for all influenza strains — but, again, with the exception of H3N2, “suggesting that the signal of possible interference may be real,” wrote Angela Branche, MD, of the University of Rochester in New York, in an accompanying editorial.

“The authors suggest this may not be clinically meaningful, but further study is needed,” she noted.

The CDC has indicated that co-administration of flu and RSV vaccines, as well as COVID-19 vaccines, is safe.

Noting that uptake of the recently approved RSV vaccines in older adults has been slow in its first season, Branche pointed to low awareness of RSV as a serious illness, vaccine fatigue, and suboptimal vaccine access. “However, equally as likely is uncertainty around the safety and effectiveness of RSV vaccines and what groups might most benefit from its use,” she wrote.

“When coupled with the increasingly crowded field of older adults’ vaccinations that include shingles, pneumococcal, influenza, COVID-19, and RSV vaccines, it’s not hard to understand why many outside the RSV scientific community have outstanding questions on how to use these vaccines,” she added.

Giving the two shots at the same time appeared to be safe overall, with most solicited adverse events being grade 1 or grade 2. Pain at vaccine sites was the most common adverse event in both groups. However, systemic adverse events — fatigue and myalgia — were more common in the co-administration group, affecting about 46% and 39% of participants, respectively.

The most frequently reported grade 3 adverse event was erythema at the injection site for the RSV vaccine, occurring in 1.9% of participants in the co-administration group and 1.3% of those in the sequential group.

One serious adverse event — giant cell arteritis — occurred in the sequential group and was considered vaccine-related. It began 10 days after receipt of the influenza vaccine, but the participant had not received the RSV vaccine. There were six fatal serious adverse events, all in the sequential group, but none were considered to be vaccine related.

This open-label trial involved 37 centers in Belgium, Finland, France, Spain, and the U.K. Of a total of 1,045 participants, 523 were randomized to the co-administration arm (mean age 72.1, 51.2% women, 99.8% white) and 522 to the sequential administration arm (mean age 72.2, 52.7% men, 98.9% white). In the sequential arm, participants received influenza and RSV vaccines 1 month apart. Vaccines were injected in the deltoid muscle, and in opposite arms when co-administered.

Of note, the trial used only GSK’s RSV vaccine and Seqirus’ influenza vaccine.

Kotb and team acknowledged that the open-label study design could have led to detection bias for reactogenicity/safety. In addition, the trial excluded people with immunocompromising conditions who are at high risk for severe RSV and influenza.

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