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Nat Commun . Redirecting antibody responses from egg-adapted epitopes following repeat vaccination with recombinant or cell culture-based versus egg

tetano

Editor, Senior Moderator
Nat Commun


. 2024 Jan 4;15(1):254.
doi: 10.1038/s41467-023-44551-x. Redirecting antibody responses from egg-adapted epitopes following repeat vaccination with recombinant or cell culture-based versus egg-based influenza vaccines

Feng Liu[SUP] 1 [/SUP], F Liaini Gross[SUP] 1 [/SUP], Sneha Joshi[SUP] 1 [/SUP], Manjusha Gaglani[SUP] 2 3 4 [/SUP], Allison L Naleway[SUP] 5 [/SUP], Kempapura Murthy[SUP] 4 [/SUP], Holly C Groom[SUP] 5 [/SUP], Meredith G Wesley[SUP] 1 6 [/SUP], Laura J Edwards[SUP] 6 [/SUP], Lauren Grant[SUP] 1 [/SUP], Sara S Kim[SUP] 1 [/SUP], Suryaprakash Sambhara[SUP] 1 [/SUP], Shivaprakash Gangappa[SUP] 1 [/SUP], Terrence Tumpey[SUP] 1 [/SUP], Mark G Thompson[SUP] 1 [/SUP], Alicia M Fry[SUP] 1 [/SUP], Brendan Flannery[SUP] 1 [/SUP], Fatimah S Dawood[SUP] 1 [/SUP], Min Z Levine[SUP] 7 [/SUP]



Affiliations
Abstract

Repeat vaccination with egg-based influenza vaccines could preferentially boost antibodies targeting the egg-adapted epitopes and reduce immunogenicity to circulating viruses. In this randomized trial (Clinicaltrials.gov: NCT03722589), sera pre- and post-vaccination with quadrivalent inactivated egg-based (IIV4), cell culture-based (ccIIV4), and recombinant (RIV4) influenza vaccines were collected from healthcare personnel (18-64 years) in 2018-19 (N = 723) and 2019-20 (N = 684) influenza seasons. We performed an exploratory analysis. Vaccine egg-adapted changes had the most impact on A(H3N2) immunogenicity. In year 1, RIV4 induced higher neutralizing and total HA head binding antibodies to cell- A(H3N2) virus than ccIIV4 and IIV4. In year 2, among the 7 repeat vaccination arms (IIV4-IIV4, IIV4-ccIIV4, IIV4-RIV4, RIV4-ccIIV4, RIV4-RIV4, ccIIV4-ccIIV4 and ccIIV4-RIV4), repeat vaccination with either RIV4 or ccIIV4 further improved antibody responses to circulating viruses with decreased neutralizing antibody egg/cell ratio. RIV4 also had higher post-vaccination A(H1N1)pdm09 and A(H3N2) HA stalk antibodies in year 1, but there was no significant difference in HA stalk antibody fold rise among vaccine groups in either year 1 or year 2. Multiple seasons of non-egg-based vaccination may be needed to redirect antibody responses from immune memory to egg-adapted epitopes and re-focus the immune responses towards epitopes on the circulating viruses to improve vaccine effectiveness.


 
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