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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 1 , F Liaini Gross 1 , Sneha Joshi 1 , Manjusha Gaglani 2 3 4 , Allison L Naleway 5 , Kempapura Murthy 4 , Holly C Groom 5 , Meredith G Wesley 1 6 , Laura J Edwards 6 , Lauren Grant 1 , Sara S Kim 1 , Suryaprakash Sambhara 1 , Shivaprakash Gangappa 1 , Terrence Tumpey 1 , Mark G Thompson 1 , Alicia M Fry 1 , Brendan Flannery 1 , Fatimah S Dawood 1 , Min Z Levine 7
Affiliations
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.
. 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 1 , F Liaini Gross 1 , Sneha Joshi 1 , Manjusha Gaglani 2 3 4 , Allison L Naleway 5 , Kempapura Murthy 4 , Holly C Groom 5 , Meredith G Wesley 1 6 , Laura J Edwards 6 , Lauren Grant 1 , Sara S Kim 1 , Suryaprakash Sambhara 1 , Shivaprakash Gangappa 1 , Terrence Tumpey 1 , Mark G Thompson 1 , Alicia M Fry 1 , Brendan Flannery 1 , Fatimah S Dawood 1 , Min Z Levine 7
Affiliations
- PMID: 38177116
- DOI: 10.1038/s41467-023-44551-x
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.