Randomized Controlled Trial, Non-Randomized Trial
Study population and setting
Conducted as a substudy of the phase 3 trial for NVX-CoV2373 (Novavax; September-November 2020), this study assessed the safety and efficacy of open label influenza vaccine coadministration with the first dose of NVXCoV2373 (n= 217) vs. placebo (n=214). Rates of minor vaccine reactions (collected via electronic diary) and adverse events were compared to a reactogenicity cohort from the main study (n=2000). Immunogenicity against influenza was assessed using a hemagglutination inhibitor assay, while that against SARS-CoV-2 was assessed by quantifying anti-spike IgG with ELISA; results were compared to an immunogenicity cohort from the main study (n=900). The primary vaccine efficacy endpoint was based on PCR detection of symptomatic SARS-CoV-2 infection at least seven days after administration of the second vaccine dose in participants aged 18 to 64 years who had not been previously infected with SARS-CoV-2 (n=360). Results were compared to vaccine efficacy for the per-protocol population of the main study age 18 to 64 years (n= 10,129), as well as vaccine efficacy against the Alpha variant for the per-protocol population of the main study (n=14,040).
Summary of Main Findings
Participants who received both vaccines had an increased frequency of minor reactions, including pain at the injection site, muscle aches, and fatigue. True adverse events were infrequent and not associated with vaccine co-administration. There was no significant change in the immune response to the influenza vaccine as a function of co-administration. However, antibody responses generated to NVX-CoV2373 were reduced among participants who had received both vaccines, as compared to those who had received only NVX-CoV2373. Vaccine efficacy in the co-administration substudy was 87.5% (CI: -0.2 – 98.4%), as compared to 89.8% (95% CI: 79.7 – 95.5%) for the main study. All substudy breakthrough infections were due to the Alpha variant; vaccine efficacy in the main study against the Alpha variant was 86.3% (95% CI: 71.3 – 93.5%).
This study employed a placebo-controlled design to assess the safety and efficacy of coadministration of vaccines for SARS-CoV-2 and influenza. Influenza vaccines were assigned based on the public health guidelines for each age group. The study included laboratory measures of immunogenicity, as well as vaccine efficacy based on breakthrough infection events.
Participation in the co-administration substudy, the reactogenicity cohort, and the immunogenicity cohort was not randomized. Substudy participants were younger, more diverse, and had fewer comorbidities than those in the main study. Influenza vaccine was administered open label to allow participants to discriminate between vaccine sites for reaction documentation. NVX-CoV2373 immunogenicity was assessed based on total antibody titer to spike protein, not neutralizing antibody titer. Due to the small number of substudy endpoint cases, 95% confidence intervals for NVX-CoV2373 efficacy were quite broad and the lower bound contained zero. The small number of breakthrough infection events also prevented the assessment of co-administered vaccine efficacy in individuals age 65 or older.
This is the first study demonstrating the safety and efficacy of coadministration of vaccines for SARS-CoV-2 and influenza.