Enhanced Influenza Vaccines Extend A(H3N2) Antibody Reactivity in Older Adults but Prior Vaccination Effects Persist

Abstract

<p>Background</p><p>Influenza vaccine effectiveness can be reduced in older adults and among repeatedly vaccinated groups. Results from year 1 of “PIVOT,” a randomized trial among adults aged ≥65 years in Hong Kong, showed that adjuvanted (Adj), high-dose (HD), and recombinant hemagglutinin (rHA) vaccines induced greater antibody responses against vaccine viruses than standard-dose (SD) influenza vaccine. Here, we examine the breadth of A(H3N2)-reactive antibodies induced during the first 2 study years (2017/2018, 2018/2019), and compare participants who received influenza vaccination annually, or not at all, for 5 years preceding enrollment.</p><p>Methods</p><p>14–20 PIVOT participants per vaccine and prior vaccination group (0/5 or 5/5 prior years) who provided sera on days 0, 30, and 182 in year 1 and days 0 and 30 in year 2 were assessed. Hemagglutination inhibition (HAI) antibody titers were measured against 30 viruses spanning 1968 to 2018.</p><p>Results</p><p>In year 1, rHA and Adj but not HD vaccines induced titers ≥40 and titer rises ≥4-fold (seroconversion) against significantly more strains than SD vaccine among participants vaccinated 0/5 prior years. Only rHA and Adj vaccines induced titers ≥40 against post-vaccine strains. Antibody responses were poor among participants vaccinated 5/5 compared with 0/5 prior years and only rHA increased the breadth of seroconversion compared with the SD vaccine in this group. Antibody responses were weaker across groups in year 2.</p><p>Conclusions</p><p>The results suggest that Adj and particularly rHA vaccines may improve the breadth of protection against A(H3N2) viruses but may not overcome attenuating effects of repeated vaccination in older adults.</p>