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Randomized Controlled Trial
. 2020 Oct 23;71(7):1704-1714.
doi: 10.1093/cid/ciz1034.

Comparative Immunogenicity of Several Enhanced Influenza Vaccine Options for Older Adults: A Randomized, Controlled Trial

Benjamin J Cowling  1 , Ranawaka A P M Perera  1 , Sophie A Valkenburg  1   2 , Nancy H L Leung  1 , A Danielle Iuliano  3 , Yat Hung Tam  1 , Jennifer H F Wong  1 , Vicky J Fang  1 , Athena P Y Li  1   2 , Hau Chi So  1 , Dennis K M Ip  1 , Eduardo Azziz-Baumgartner  3 , Alicia M Fry  3 , Min Z Levine  3 , Shivaprakash Gangappa  3 , Suryaprakash Sambhara  3 , Ian G Barr  4   5 , Danuta M Skowronski  6   7 , J S Malik Peiris  1 , Mark G Thompson  3
Affiliations
Randomized Controlled Trial

Comparative Immunogenicity of Several Enhanced Influenza Vaccine Options for Older Adults: A Randomized, Controlled Trial

Benjamin J Cowling et al. Clin Infect Dis. .

Abstract

Background: Enhanced influenza vaccines may improve protection for older adults, but comparative immunogenicity data are limited. Our objective was to examine immune responses to enhanced influenza vaccines, compared to standard-dose vaccines, in community-dwelling older adults.

Methods: Community-dwelling older adults aged 65-82 years in Hong Kong were randomly allocated (October 2017-January 2018) to receive 2017-2018 Northern hemisphere formulations of a standard-dose quadrivalent vaccine, MF59-adjuvanted trivalent vaccine, high-dose trivalent vaccine, or recombinant-hemagglutinin (rHA) quadrivalent vaccine. Sera collected from 200 recipients of each vaccine before and at 30-days postvaccination were assessed for antibodies to egg-propagated vaccine strains by hemagglutination inhibition (HAI) and to cell-propagated A/Hong Kong/4801/2014(H3N2) virus by microneutralization (MN). Influenza-specific CD4+ and CD8+ T cell responses were assessed in 20 participants per group.

Results: Mean fold rises (MFR) in HAI titers to egg-propagated A(H1N1) and A(H3N2) and the MFR in MN to cell-propagated A(H3N2) were statistically significantly higher in the enhanced vaccine groups, compared to the standard-dose vaccine. The MFR in MN to cell-propagated A(H3N2) was highest among rHA recipients (4.7), followed by high-dose (3.4) and MF59-adjuvanted (2.9) recipients, compared to standard-dose recipients (2.3). Similarly, the ratio of postvaccination MN titers among rHA recipients to cell-propagated A(H3N2) recipients was 2.57-fold higher than the standard-dose vaccine, which was statistically higher than the high-dose (1.33-fold) and MF59-adjuvanted (1.43-fold) recipient ratios. Enhanced vaccines also resulted in the boosting of T-cell responses.

Conclusions: In this head-to-head comparison, older adults receiving enhanced vaccines showed improved humoral and cell-mediated immune responses, compared to standard-dose vaccine recipients.

Clinical trials registration: NCT03330132.

Keywords: influenza; public health; vaccination.

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Conflict of interest statement

Potential conflicts of interest. B. J. C. has received honoraria from Sanofi and Roche for advisory committees. All other authors report no potential conflicts. 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.
Flow chart of participants through the study, and selection of 200 participants per group for serologic analysis. Abbreviations: D, day; HA, hemagglutinin; QIV, quadrivalent influenza vaccine; TIV, trivalent influenza vaccine.
Figure 2.
Figure 2.
Comparisons of postvaccination geometric mean antibody titers in each of the enhanced vaccine groups, compared to the postvaccination geometric mean titer in the standard-dose QIV group (n = 200 individuals per group). Values significantly different from 1.0 are highlighted in bold. Note that a B/Yamagata lineage virus was not included in the MF59-adjuvanted TIV and the high-dose TIV. Antigens used were A/Singapore/GP1908/2015 (A/Michigan/45/2015[H1N1]-like virus); A/Hong Kong/4801/2014(H3N2), with both egg-propagated and cell-propagated variants; B/Brisbane/60/2008; and B/Phuket/3073/2013. Abbreviations: CI, confidence interval; GMT, geometric mean titer; GMTR, geometric mean titer ratio comparing post-vaccination geometric mean titers between enhanced vaccine groups and the standard dose group; HA, hemagglutinin; HAI, hemagglutination inhibition assay; MN, microneutralization assay; QIV, quadrivalent influenza vaccine; TIV, trivalent influenza vaccine.
Figure 3.
Figure 3.
The mean and standard deviations of the fold changes of Days 7 and 30 IFN-γ+ T cells, compared to Day 0 responses for A/Michigan/45/2015(H1N1), A/Switzerland/9715293/2013(H3N2), and B/Brisbane/60/2008 viruses after in vitro stimulation for (A) CD8+ and (B) CD4+ IFN-γ+ T cells (n = 20 individuals per group). Values marked with a # symbol indicate a statistically significant difference (P < .05), compared to the response in the standard-dose vaccine group at the same time point. Values marked with an * indicate a statistically significant difference (P < .05), compared to the baseline (Day 0) response within the same vaccine group. Abbreviations: D, day; HA, hemagglutinin; IFN, interferon.
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