VaccineDec 11, 2025

Immune response to mRNA COVID-19 vaccine given at the same time or after flu shots: a randomized trial

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

Simultaneous inactivated influenza vaccination did not blunt measured mRNA COVID-19 vaccine antibody responses.

Evidence

This U.S. multisite randomized clinical trial compared simultaneous versus 7-14 day sequential IIV4 administration in 335 persons aged at least 5 years receiving an initial or booster mRNA COVID-19 vaccine dose.

Caveat

The abstract reports 28-day pseudovirus neutralization titers, not clinical protection or longer-term immune durability.

Simplified

BACKGROUND: A U.S. multisite trial was conducted and explored whether blunting of mRNA COVID-19 vaccine immunogenicity occurred when administered simultaneously with influenza vaccine.

METHODS: Persons ≥5 years of age received either quadrivalent inactivated influenza vaccine (IIV4) or saline placebo simultaneously with an initial or booster dose of mRNA COVID-19 vaccine. Those receiving placebo with mRNA COVID-19 vaccine received IIV4 7-14 days later. SARS-CoV-2 antibody was assessed by pseudovirus neutralization (D614G, BA.4/BA. 5, and XBB.1.5) at baseline and 28 days following mRNA COVID-19 vaccine primary series or booster dose.

RESULTS: Of 335 randomized participants, 157 were in the simultaneous group and 150 the sequential group. Post-vaccination geometric mean SARS-CoV-2 ID50 titers for the ancestral D614G strain and BA.4/5 variant (simultaneous versus sequential) were 4357.1 versus 4492.3(p = 0.79) and 1547.8 versus 1463.8(p = 0.69), respectively.

CONCLUSION: Blunting of mRNA COVID-19 vaccine immunogenicity was not observed when mRNA COVID-19 and influenza vaccines were administered simultaneously. TRIAL REGISTRATIONClinicalTrials.gov ID: NCT05028361.