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

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.

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.

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.

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.