Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Oct 5;77(7):1032-1042.
doi: 10.1093/cid/ciad322.

High-Dose Influenza Vaccine Is Associated With Reduced Mortality Among Older Adults With Breakthrough Influenza Even When There Is Poor Vaccine-Strain Match

Sandra S Chaves  1 , Sarah Naeger  1 , Kahina Lounaci  2 , Yue Zuo  2 , Matthew M Loiacono  3 , Quentin Pilard  2 , Joshua Nealon  4 , Marie Genin  2 , Cedric Mahe  1
Affiliations

High-Dose Influenza Vaccine Is Associated With Reduced Mortality Among Older Adults With Breakthrough Influenza Even When There Is Poor Vaccine-Strain Match

Sandra S Chaves et al. Clin Infect Dis. .

Abstract

Background: High-dose (HD) influenza vaccine offers improved protection from influenza virus infection among older adults compared with standard-dose (SD) vaccine. Here, we explored whether HD vaccine attenuates disease severity among older adults with breakthrough influenza.

Methods: This was a retrospective cohort study of US claims data for influenza seasons 2016-2017, 2017-2018, and 2018-2019, defined as 1 October through 30 April, among adults aged ≥65 years. After adjusting the different cohorts for the probability of vaccination conditional on patients' characteristics, we compared 30-day mortality rate post-influenza among older adults who experienced breakthrough infection after receipt of HD or SD influenza vaccines and among those not vaccinated (NV).

Results: We evaluated 44 456 influenza cases: 23 109 (52%) were unvaccinated, 15 037 (33.8%) received HD vaccine, and 6310 (14.2%) received SD vaccine. Significant reductions in mortality rates among breakthrough cases were observed across all 3 seasons for HD vs NV, ranging from 17% to 29% reductions. A significant mortality reduction of 25% was associated with SD vaccination vs NV in the 2016-2017 season when there was a good match between circulating influenza viruses and selected vaccine strains. When comparing HD vs SD cohorts, mortality reductions were higher among those who received HD in the last 2 seasons when mismatch between vaccine strains and circulating H3N2 viruses was documented, albeit not significant.

Conclusions: HD vaccination was associated with lower post-influenza mortality among older adults with breakthrough influenza, even during seasons when antigenically drifted H3N2 circulated. Improved understanding of the impact of different vaccines on attenuating disease severity is warranted when assessing vaccine policy recommendations.

Keywords: breakthrough influenza; disease attenuation; high-dose influenza vaccine; influenza; severe influenza.

PubMed Disclaimer

Conflict of interest statement

Potential conflicts of interest. S. S. C., S. N., M. M. L., and C. M. are employees of Sanofi. K. L., M. G., Q. P., and Y. Z. report consulting fees from Sanofi (Quinten Health was contracted by Sanofi). C. M., J. N., and M. M. L may hold Sanofi shares. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Patient cohort selection process. Abbreviations: HD, high-dose influenza vaccine; NV, not vaccinated; SD, standard-dose influenza vaccine.
Figure 2.
Figure 2.
Box plot showing distribution of the absolute standard mean differences for the raw data compared with PSM, PTW, and entropy balancing. Each comparison group is represented by high-dose vs nonvaccinated (A), high-dose vs standard-dose (B), and standard-dose vs not vaccinated (C). The first panel represents the 2016–2017 season, the second panel represents the 2017–2018 season, and the last panel represents the 2018–2019 season. Abbreviations: IPTW, inverse probability treatment weighting; PSM, propensity score matching.
Figure 3.
Figure 3.
Absolute standard mean difference for each covariate using the entropy balancing method. The columns represent the 2016–2017, 2017–2018, and 2018–2019 seasons. The rows represent high-dose vs no vaccine, high-dose vs standard-dose, and standard-dose vs no vaccine.
Figure 4.
Figure 4.
A, Forest plot showing the relative risk (RR), 95% CI, P value, and percentage reduction in risk of death for each season after entropy balancing for each comparison cohorts. B, The distribution of influenza viruses by type and subtype in each study season [28, 31, 32]. Abbreviations: CI, confidence interval; HD, high-dose influenza vaccine; IRR, incidence rate ratio; LL, lower limit; NV, not vaccinated; SD, standard-dose influenza vaccine; UL, upper limit.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Centers for Disease Control and Prevention. Disease burden of flu. Available at: https://www.cdc.gov/flu/about/burden/index.html#:∼:text=While%20the%20ef.... Accessed 9 June 2022.
    1. Belongia EA, Simpson MD, King JP, et al. . Variable influenza vaccine effectiveness by subtype: a systematic review and meta-analysis of test-negative design studies. Lancet Infect Dis 2016; 16:942–51. - PubMed
    1. Falsey AR, Treanor JJ, Tornieporth N, Capellan J, Gorse GJ. Randomized, double-blind controlled phase 3 trial comparing the immunogenicity of high-dose and standard-dose influenza vaccine in adults 65 years of age and older. J Infect Dis 2009; 200:172–80. - PubMed
    1. DiazGranados CA, Dunning AJ, Kimmel M, et al. . Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med 2014; 371:635–45. - PubMed
    1. Grohskopf LA, Alyanak E, Ferdinands JM, et al. . Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices, United States, 2021–22 influenza season. MMWR Recomm Rep 2021; 70:1–28. - PMC - PubMed

Publication types

Substances