Waning intra-season vaccine effectiveness against influenza A(H3N2) underlines the need for more durable protection

ABSTRACT

Background

The question of whether influenza vaccine effectiveness (VE) wanes over the winter season is still open and some contradictory findings have been reported. This study investigated the possible decline in protection provided by the available influenza vaccines.

Research design and methods

An individual-level pooled analysis of six test-negative case-control studies conducted in Italy between the 2018/2019 and 2022/2023 seasons was performed. Multivariable logistic regression analyses were performed to estimate weekly change in the odds of testing positive for influenza 14 days after vaccination.

Results

Of 6490 patients included, 1633 tested positive for influenza. Each week that had elapsed since vaccination was associated with an increase in the odds of testing positive for any influenza (4.9%; 95% CI: 2.0–8.0%) and for A(H3N2) (6.5%; 95% CI: 2.9–10.3%). This decline in VE was, however, significant only in children and older adults. A similar increase in the odds of testing positive was seen when the dataset was restricted to vaccinees only. Conversely, VE waning was less evident for A(H1N1)pdm09 or B strains.

Conclusions

Significant waning of VE, especially against influenza A(H3N2), may be one of the factors associated with suboptimal end-of-season VE. Next-generation vaccines should provide more durable protection against A(H3N2).

KEYWORDS:

• Influenza
• influenza vaccines
• vaccine effectiveness
• waning
• A(H3N2) subtype

Declaration of interests

A Domnich provided consultation and received speaker fees from CSL Seqirus, GSK and SD Biosensor. A Orsi provided consultation and/or received speaker fees from CSL Seqirus, Moderna, Novavax and SD Biosensor. D Panatto provided consultation for Pfizer and CSL Seqirus and received grants to conduct observational studies from Sanofi, Pfizer, GSK and Viatris. C Rizzo provided consultation and received speaker fees from CSL Seqirus, GSK, MSD, AstraZeneca and Sanofi. G Icardi provided consultation and/or received grants to conduct experimental and/or observational studies for GSK, Sanofi, MSD, CSL Seqirus and Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article. All authors contributed to study conception and design, data acquisition, analysis, and interpretation, drafting and revising of the manuscript.

Ethical approval and patient consent

All studies have been approved by the pertinent ethics committees. All participants have provided written informed consent.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14760584.2024.2331073.

Additional information

Funding

Part of this manuscript was funded by the DRIVE project, which has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777363. This Joint Undertaking receives support from the European Union’s Horizon 2020 Research and Innovation program and EFPIA.