Receiving COVID-19 and seasonal influenza vaccines at the same time was found to be both safe and effective, with little change in immune response reported in a sub-study of the phase III trial of the NVX-CoV2373 COVID-19 vaccine (Novavax). Co-administration of the NVX-CoV2373 vaccine and flu vaccine was associated with only a slight reduction in the COVID-19 vaccine’s efficacy, and no serious adverse events were reported in study participants receiving the two shots at the same time. The sub-study, published in Lancet Respiratory Medicine, is among the first to examine the safety, immunogenicity, and efficacy of co-administration of a COVID-19 vaccine and seasonal flu shot.

Co-Administration Endorsements

The CDC has endorsed the co-administration of COVID-19 vaccines and non-COVID vaccines, noting in a directive that “COVID-19 vaccines may be administered without regard to the timing of other vaccines.” In earlier guidance, however, CDC officials recommended a 2-week interval between administration of COVID-19 and influenza vaccines. Health agencies in other countries, including the UK, also advised against co-administration of the vaccines in the early months of COVID-19 vaccine availability. The WHO also weighed in, concluding that co-administration of any COVID-19 and inactivated seasonal flu vaccine is acceptable, “given that the known risk of serious illness for adults infected with influenza virus or SARS-CoV-2 is substantial.”

Writing in Lancet Respiratory Medicine, researcher Seth Toback, MD, and colleagues noted that the sub-study findings provide “much needed information to help guide national immunization policy decision making on the important issue of concomitant use of COVID-19 vaccines with influenza vaccines.”

Conferring the Confidence to Trial New Protocols

In accompanying commentary, immunologists Daniel Altmann, PhD, and Rosemary Boyton, PhD, of Imperial College London, wrote that the early caution regarding vaccine co-administration was understandable. “At the time of rolling out new vaccines at such a fast pace while trying to maintain a high bar for safety, a high degree of caution was warranted in the uncharted territory of vaccine co-administration,” they wrote. They added that the lessons learned from COVID-19 vaccine programs challenge “long held but poorly evidenced assumptions” about the risks associated with vaccine co-administration, including the theory that the immune system might be overloaded by exposure to simultaneous vaccines.

Drs. Altmann and Boyton wrote that the assumption, widely known by the term “vaccine interference… was always mystifying to basic immunologists used to thinking of a person’s immune repertoire as having the ability to generate several billion B-cell receptor sequences (each of which triggers production of specific antibodies).” The commentary writers concluded that COVID-19 vaccine development has “turbo-charged the whole of vaccinology, conferring the confidence to trial new protocols and protect against diverse pathogens—even if this means administering the different vaccines at the same time.”

Sub-Study Details

The newly published sub-study involved 431 of the original 2019nCoV-302 phase III study participants (N=15,187) randomized to receive the NVX-CoV2373 vaccine (N=217) or placebo (N=214) co-administered with a seasonal influenza vaccine. Compared with the overall study population, the sub-study participants tended to be younger, more racially diverse, and have fewer comorbidities. Primary study endpoints included safety, immunogenicity, and efficacy of the NVX-CoV2373 vaccine when given with seasonal flu vaccine.

Reactogenicity was analyzed in all participants who received at least one dose of the COVID-19 vaccine or placebo and had data collected for reactogenicity. Reactogenicity events—including tenderness at the injection site, fatigue, and muscle pain— were found to be more common in the co-administration group than in the NVX-CoV2373 alone group (tenderness, 64.9% vs 53.3%; fatigue, 27.7% vs 19.4%; muscle pain, 28.3% vs 21.4%), but serious adverse events were rare, with no significant difference reported between the two groups. No episodes of anaphylaxis or deaths were reported within the sub-study.

Co-administration resulted in no change to influenza vaccine immune response, although a slight reduction in antibody responses to the NVX-CoV2373 vaccine was noted. NVX-CoV2373 vaccine efficacy in the sub-study among adult participants younger than 65 was 87.5% (95% CI, –0.2-98.4), compared with 89.8% (95% CI, 79.7-95.5) in the main study.

“This substudy is the first to show the safety, immunogenicity, and efficacy profile of a COVID-19 vaccine when co-administered with a seasonal influenza vaccine,” the researchers wrote. “These data show no early safety concerns with the concomitant administration of NVX-CoV2373 with an influenza vaccine. Immunogenicity of the influenza vaccine was preserved with concomitant administration although a modest decrease in the immunogenicity of the NVX-CoV2373 vaccine was found.”

Dr. Toback and colleagues concluded that “future clinical trials and post-licensure studies of COVID-19 vaccines should include safety and immunogenicity data for co-administration with common adult and pediatric vaccines.More research on the concomitant administration of COVID-19 and influenza vaccines is needed, especially in those older than 65, to help guide national immunization policy on this important issue.”