TOPLINE:

Egg- and non-egg-based influenza vaccines showed equivalent protection against laboratory-confirmed influenza‑like illness and related hospitalizations among healthy adults in the military health system. However, recombinant influenza vaccine achieved higher seroconversion rates across all influenza subtypes.

METHODOLOGY:

• Researchers conducted a randomized trial to compare the effectiveness of a cell culture-based inactivated influenza vaccine and a recombinant influenza vaccine with that of an egg-based inactivated influenza vaccine among military health system beneficiaries over four influenza seasons from 2018 to 2022.
• A total of 15,432 participants (32.1% women; 79% younger than 45 years) across ten US sites were randomly assigned to a control group that received the egg-based inactivated vaccine (n = 5148) or to test groups that received the cell culture-based inactivated vaccine (n = 5130) or the recombinant vaccine (n = 5154).
• Participants completed weekly text or email surveys beginning 2 weeks after vaccination, reporting any influenza-like illness symptoms over the past 7 days; a nasal swab and a blood sample were collected if influenza-like illness was reported.
• The primary outcome was laboratory-confirmed influenza, detected by reverse transcription polymerase chain reaction from study-collected swabs or positive clinical tests at least 14 days post-vaccination.
• A secondary aim of the study was to compare the immunogenicity of the cell culture-based and recombinant vaccines with that of the egg-based vaccine in a subset of 1087 participants, with samples taken before vaccination and 21-35 days post-vaccination.

TAKEAWAY:

• Influenza occurred in 1.7% of cell culture-based vaccine recipients, 1.5% of recombinant vaccine recipients, and 1.3% of egg-based vaccine recipients; most laboratory-confirmed cases were due to subtype influenza A.
• No significant difference in vaccine effectiveness was seen between the cell culture-based and egg-based vaccines (relative vaccine effectiveness [rVE], -26.53%; 95% CI, -73.13% to 7.53%) or between the recombinant and egg-based vaccines (rVE, -14.36%; 95% CI, -57.59% to 17.01%).
• Recombinant vaccine recipients achieved higher seroconversion rates than egg-based recipients across all subtypes, whereas cell culture-based vaccine recipients achieved higher seroconversion rates than egg-based recipients only for virus subtype A/H3N2.
• When egg-based vaccines were compared with either cell culture-based or recombinant vaccines, no significant differences in rVE were observed for influenza subtypes, influenza-like illness, or related hospitalizations.

IN PRACTICE:

“This study did not detect significant differential effectiveness of newer non-egg-based influenza vaccines compared to egg-based products in preventing influenza illness in a population of predominantly healthy, working-age adults with low influenza incidence,” the authors wrote.

SOURCE:

This study was led by Rhonda E. Colombo, MD, MHS, from the Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland. It was published online on September 18, 2025, in Clinical Infectious Diseases.

LIMITATIONS:

This study was limited by the small number of influenza cases, and the wide CIs around rVE point estimates indicated that a higher infection rate might have uncovered clinically meaningful differences. The open-label design may have introduced bias, and the largely young, healthy sample limited generalizability to older adults or those with comorbidities.

DISCLOSURES:

This study received federal funding from multiple sources, including the Defense Health Program, the US Department of Defense, the Defense Health Agency Immunization Healthcare Division, among others. Some authors disclosed receiving research funding or consulting fees from, being employed by, or serving as speakers for various pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.