Serologic response to sequential vaccination with enhanced influenza vaccines: Open label randomized trial among adults aged 65-74 years

Background: The effects of sequential vaccination with enhanced influenza vaccines are poorly under-stood. We conducted an exploratory open-label study to assess serologic response to sequential vaccina-tion in older adults. Methods: 160 adults aged 65 through 74 years were randomized (1:1:1) to receive trivalent inactivated standard dose (SD), high-dose (HD), or MF59-adjuvanted (AD) vaccine in 2016/17. In 2017/18, HD and AD recipients received the same vaccine; SD recipients were re-randomized to HD or AD. Hemagglutination inhibition assays were performed using turkey erythrocytes against A/California/7/2009(H1N1)-like and B/Brisbane/60/2008(B/Victoria)-like in both seasons, and A/Michigan/45/2015(H1N1)-like in season 2. Microneutralization assays were performed against cell-propagated A/Hong Kong/4801/2014(H3N2)-like using MDCK-SIAT1 cells. Postvaccination geometric mean titer (GMT), percent with titer > 40, and mean fold rise (MFR, ratio of postvaccination versus prevaccination titer) in season 2 were compared across groups, and ratio of MFR in season 2 versus season 1 was assessed for each strain. Results: Analysis included 152 participants (55 HD-. HD, 58 AD-. AD, 19 SD-. HD, and 20 SD-. AD). Season 2 postvaccination GMTs and percent with titer > 40 did not differ between HD-. HD and AD-. AD recipients for vaccine strains examined. However, a higher percent of HD-. HD and AD-. AD recipients had postvaccination titer > 40 than SD-. AD recipients for A/H1N1 (86%-89% versus 60%) and SD-. AD and SD-. HD recipients for A/H3N2 (83%-87% versus 40%-53%). GMTs were higher in AD-. AD versus SD-. AD recipients for A/H1N1 (p = .01) and A/H3N2 (p = .002). MFRs in season 2 were low in all groups for A/H3N2 (1.5-2.2) and B/Victoria (1.7-2.3). MFR was lower in season 2 versus 1 for HD-. HD and AD-. AD recipients for all vaccine strains (1.6-3.7 versus 2.6-6.2). Conclusions: Sequential vaccination with enhanced vaccines did not reduce immunogenicity in adults aged 65 through 74 years. Serologic response to cell-propagated A/H3N2 was suboptimal for all vaccines. ClinicalTrials.gov identifier. NCT02872311 (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).