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

tetano

Editor, Senior Moderator
Clin Infect Dis


. 2025 Apr 3:ciaf060.
doi: 10.1093/cid/ciaf060. Online ahead of print. Enhanced Influenza Vaccines Extend A(H3N2) Antibody Reactivity in Older Adults but Prior Vaccination Effects Persist

Annette Fox[SUP] 1 2 [/SUP], Stephany Sánchez-Ovando[SUP] 1 2 [/SUP], Louise Carolan[SUP] 2 [/SUP], A Jessica Hadiprodjo[SUP] 1 2 [/SUP], Yuyun Chen[SUP] 3 [/SUP], Faith Ho[SUP] 3 [/SUP], Samuel M S Cheng[SUP] 3 [/SUP], Mark G Thompson[SUP] 4 [/SUP], A Danielle Iuliano[SUP] 4 [/SUP], Min Z Levine[SUP] 4 [/SUP], Sophie A Valkenburg[SUP] 5 6 [/SUP], Dennis K M Ip[SUP] 3 [/SUP], J S Malik Peiris[SUP] 3 7 [/SUP], Sheena G Sullivan[SUP] 1 2 8 [/SUP], Benjamin J Cowling[SUP] 3 9 [/SUP], Nancy H L Leung[SUP] 3 9 [/SUP]



Affiliations
Abstract

Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Clinical trials registration: NCT03330132.

Keywords: immunogenicity; influenza; older adults; public health; vaccination.

 
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