Protection against influenza hospitalizations from enhanced influenza vaccines among older adults: A systematic review and network meta-analysis

Abstract

Background: Influenza vaccines are available to help protect persons aged ≥65 years, who experience thousands of influenza hospitalizations annually. Because some influenza vaccines may work better than others, we sought to assess benefit of high-dose (HD), adjuvanted (ADJ), and recombinant (RIV) influenza vaccines ("enhanced influenza vaccines") compared with standard-dose unadjuvanted influenza vaccines (SD) and with one another for prevention of influenza-associated hospitalizations among persons aged ≥65 years.

Methods: We searched MEDLINE, Embase, CINAHL, Scopus, and Cochrane Library to identify randomized or observational studies published between January 1990 and October 2023 and reporting relative vaccine effectiveness (rVE) of HD, ADJ, or RIV for prevention of influenza-associated hospitalizations among adults aged ≥65 years. We extracted study data, assessed risk of bias, and conducted random-effects network meta-analysis and meta-regression.

Results: We identified 32 studies with 90 rVE estimates from five randomized and 27 observational studies (71,459,918 vaccinated participants). rVE estimates varied across studies and influenza seasons. Pooled rVE from randomized studies was 20% (95% CI -54 to 59) and 25% (95% CI -19 to 53) for ADJ and HD compared with SD, respectively; rVE was 6% (95% CI -109 to 58) for HD compared with ADJ; these differences were not statistically significant. In observational studies, ADJ, HD, and RIV conferred modestly increased protection compared with SD (rVE ranging from 10% to 19%), with no significant differences between HD, ADJ, and RIV. With enhanced vaccines combined, rVE versus SD was 18% (95% CI 3 to 32) from randomized and 11% (95% CI 8 to 14) from observational evidence. Meta-regression of observational studies suggested that those requiring laboratory confirmation of influenza reported greater benefit of enhanced vaccines.

Conclusions: HD, ADJ, and RIV provided stronger protection than SD against influenza hospitalizations among older adults. No differences in benefit were observed in comparisons of enhanced influenza vaccines with one another.

Keywords: adjuvanted influenza vaccine; adjuvants; administration and dosage; aged; high‐dose trivalent influenza vaccine; immunologic; influenza vaccines; network meta‐analysis; recombinant influenza vaccine.

FIGURE 1

PICO elements of this systematic review.

FIGURE 2

Network meta‐analysis plot of randomized evidence. The thickness of the line connecting a pair of vaccines is proportional to the number of direct comparisons between them and the size of the node is proportional to the total number of study participants in each vaccine group.

FIGURE 3

Forest plot of random‐effects network meta‐analysis results from (A) five randomized trials and (B) 27 observational studies, showing estimated mean relative vaccine effectiveness for prevention of influenza‐associated hospitalizations for pairwise comparisons of vaccine types. The 95% prediction intervals for each comparison are also shown. ADJ, adjuvanted inactivated influenza vaccine; HD, high‐dose inactivated influenza vaccine; RIV, recombinant influenza vaccine; SD, standard‐dose inactivated influenza vaccine; VE, vaccine efficacy/effectiveness.

FIGURE 4

Network meta‐analysis plot for observational evidence. The thickness of the line connecting a pair of vaccines is proportional to the number of direct comparisons between them and the size of the node is proportional to the total number of study participants in each vaccine group.