New clinical trial is first to describe concomitant administration of any vaccine with either an adenoviral vector or mRNA COVID-19 vaccine.
The first clinical trial to assess concomitant administration of any vaccine with either an adenoviral vector or mRNA COVID-19 vaccine found the combination with influenza vaccine is safe, produces immunogenicity associated with separate vaccination, and supports the combination as an efficient intervention against the possible "twindemic."
Validation of a more efficient means to vaccinate against these viral infections is particularly welcome as flu season has commenced in the US and northern hemisphere countries, and a recent survey from the National Foundation for Infectious Diseases (NFID) shows that 44% of the US population are unsure or do not plan to get vaccinated against influenza.
Rajeka Lazarus, DPhil, Department of Microbiology, University Hospitals Bristol and Weston, NHS Foundation Trust, Bristol, UK, and colleagues of the ComFluCOV Trial Group anticipate that concomitant administration would reduce burden on healthcare systems, and report, "concomitant vaccination raises no safety concerns and preserves the immune response to both vaccines."
The investigators recruited 679 participants who had received the first dose of either the adenoviral vector SARS-CoV-2 vaccine ChAd0x1 (AstraZeneca) or the mRNA vaccine BNT162b2 (Pfizer-BioNTech) and randomized 1:1 to receive either placebo or an age-appropriate dosed influenza vaccine (adjuvanted trivalent or cellular or recombinant quadrivalent) with their second COVID-19 vaccine dose.Follow-up monitoring was available for 665 participants.
The study monitored for adverse effects and assessed laboratory indicators of immunogenicity from April 1 through June 26, 2021, outside influenza season.The study was interrupted April 8 when notice was received of thomboembolic events associated with ChAd0x1, and resumed April 9 with exclusion of participants with risk factors for thrombotic events.
The primary outcome was one or more solicited reports of systemic reaction within 7 days after vaccination such as fever, chills, or joint pains. Secondary outcomes involving safety and adverse response included solicited local reactions such as pain or tenderness and unsolicited adverse events, including medically-attended adverse events.
The secondary outcome of immune response was determined from measures including SARS-CoV-2 S-protein immunoglobulin G (anti-S IgG) concentration in serum collected on day of vaccination (D0) and day 21; and hemagglutinin antibody inhibition (HAI) against the 4 strains of influenza contained in the 2020/21 formulations, on D0, day 21 and day 42. Other immunological measures that will be in a subsequent report include neutralizing antibodies against SARS-CoV-2 on D0 and day 21 and mucosal immune responses to COVID-19 vaccines in saliva.
Lazarus and colleagues reported that, overall, 555/665 (83.5%) of participants had at least one solicited local adverse reaction after vaccination on DO; in 85.2% of those receiving concomitant vaccinations and 81.7% with placebo in lieu of influenza.The numbers with local reactions 7 days after injection were similar in both groups, although higher among those receiving the active combination at day 21.Rates of medically assisted adverse events were similar between groups following both D0 and day 21.
The Anti-S IgG geometric mean units (GMU) at day 21 were similar between those who received either SARS-CoV-2 vaccine alone or with concomitant influenza vaccine.Seroconversion rates (SCR) ranged from 89-100% and 79-93% 21 days after either BNT162b2 or CHAd0x1, respectively, whether administered alone or in combination with influenza vaccine.There were no significant differences in the HAI GMR for any influenza strain 21 days after influenza concomitant vaccination with SARS-CoV-2 vaccine compared to previously studied cohorts receiving influenza vaccination alone.
"By performing the trial in relation to the second rather than the first dose of COVID-19 vaccine, we have evaluated safety and immunogenicity in primed individuals," Lazarus and colleagues point out."Therefore, the findings are also likely to be more relevant to the question of concomitant administration of booster doses and seasonal influenza vaccines, which over time may become the 'norm' in many parts of the world."