Safety and Immunogenicity of the BNT162b2 Vaccine Coadministered with Seasonal Inactivated Influenza Vaccine in Adults

Abstract

Introduction: Vaccination is a critical tool for preventing coronavirus disease 2019 (COVID-19) and influenza illnesses. Coadministration of the COVID-19 vaccine, BNT162b2, with seasonal inactivated influenza vaccine (SIIV) can provide substantial benefits, including streamlining vaccine delivery.

Methods: In this phase 3 study, healthy 18- to 64-year-olds who had received three previous doses of BNT162b2 were randomized (1:1) to the coadministration group (month 0, BNT162b2 + SIIV; month 1, placebo) or the separate-administration group (month 0, placebo + SIIV; month 1, BNT162b2). The primary immunogenicity objective was to demonstrate that the immune responses elicited by BNT162b2 and SIIV [measured by full-length S-binding immunoglobulin G (IgG) levels and strain-specific hemagglutination inhibition assay (HAI) titers against four influenza strains 1 month post-vaccination, respectively] when coadministered were noninferior to those elicited by either vaccine administered alone, based on a prespecified 1.5-fold noninferiority margin [lower bound 95% CI for geometric mean ratio (GMR) > 0.67]. Reactogenicity and adverse event (AE) rates were evaluated.

Results: Randomized participants who received study vaccination (N = 1128; coadministration group, n = 564; separate-administration group, n = 564) had a median age of 39 years. Model-adjusted GMRs for coadministration to separate administration were 0.83 (95% CI 0.77, 0.89) for full-length S-binding IgG levels and 0.89-1.00 (lower bound of all 95% CIs > 0.67) for the four influenza strain-specific HAI titers, with all endpoints achieving the prespecified noninferiority criterion. Reactogenicity events were mostly mild or moderate when BNT162b2 was coadministered with SIIV. Serious AEs were reported in < 1% of participants within 1 month after any vaccination; none were considered vaccine-related.

Conclusions: BNT162b2 coadministered with SIIV elicited immune responses that were noninferior to those elicited by BNT162b2 alone and SIIV alone, and BNT162b2 had an acceptable safety profile when coadministered with SIIV. The results of this study support the coadministration of BNT162b2 and SIIV in adults.

Trial registration: ClinicalTrials.gov registration: NCT05310084.

Keywords: BNT162b2; COVID-19; Clinical trial; Coadministration; Immunogenicity; Influenza; Safety; Seasonal inactivated influenza vaccine; Vaccination.

Fig. 1

Study design. SIIV seasonal inactivated influenza vaccine

Fig. 2

Randomization and vaccine administration. AE adverse event, SIIV seasonal inactivated influenza vaccine

Fig. 3

Comparison of coadministration group to separate-administration group of model-adjusted GMRs for the SARS-CoV-2 full-length S-binding IgG levels and influenza strain-specific HAI titers. Data are for the evaluable BNT162b2 immunogenicity population and evaluable SIIV immunogenicity population (defined in Table S1); 95% CIs were based on analysis of logarithmically transformed assay results using a linear regression model that included vaccine group, age group, and corresponding baseline assay results as covariates. Assay results below the LLOQ were set to 0.5 × LLOQ (S-binding IgG and HAI) and results above the ULOQ were set to ULOQ + 1 (HAI only). The dotted line represents the prespecified noninferiority margin. The number of participants with valid and determinate results for the specified assay at both baseline and the given sampling timepoint was 499 in the coadministration group and 413 in the separate-administration group for full-length S-binding IgG levels, and 508–515 and 478–484, respectively, for HAI titers. GMR geometric mean ratio, HAI hemagglutination inhibition assay, IgG immunoglobulin G, LLOQ lower limit of quantitation, S spike protein, SIIV seasonal inactivated influenza vaccine, ULOQ upper limit of quantitation

Fig. 4

A GMCs and GMFRs for SARS-CoV-2 full-length S-binding IgG and B GMTs and GMFRs for strain-specific HAI titers from before vaccination to 1 month after vaccination. Data are for the evaluable BNT162b2 immunogenicity population and evaluable SIIV immunogenicity population. Two-sided 95% CIs for GMCs, GMTs, and GMFRs were based on the Student’s t-distribution. In each vaccine group, the number of participants with valid and determinate assay results for the specified assay was 413–499 in the evaluable BNT162b2 immunogenicity population and 478–520 in the evaluable SIIV immunogenicity population. GMC geometric mean concentration, GMFR geometric mean-fold rise, GMT geometric mean titer, HAI hemagglutination inhibition assay, IgG immunoglobulin G, SIIV seasonal inactivated influenza vaccine

Fig. 5

A Local reactions and B systemic events reported within 7 days of vaccination. Data are for the safety population. Severity grading of the specific local reactions and systemic events is provided in Table S4. Error bars represent 95% CIs, and numbers above the bars indicate the percentage of participants in each group reporting the specified event. Local reactions were assessed by participants at the BNT162b2 or placebo injection site only. Coadmin (vax 1) = BNT162b2 + SIIV (n = 564); coadmin (vax 2) = placebo (n = 557); separate (vax 1) = SIIV + placebo (n = 562–563); separate (vax 2) = BNT162b2 (n = 553). SIIV seasonal inactivated influenza vaccine

Fig. 6

Adverse events by category reported within 1 month after each vaccination. Data are for the safety population. The numbers above the bars show the percentage of participants who experienced ≥ 1 of the specified type of event after the respective vaccination. AE adverse event, SIIV seasonal inactivated influenza vaccine