Redirecting antibody responses from egg-adapted epitopes following repeat vaccination with recombinant or cell culture-based versus egg-based influenza vaccines

Feng Liu, F. Liaini Gross, Sneha Joshi, Manjusha Gaglani, Allison L. Naleway, Kempapura Murthy, Holly C. Groom, Meredith G. Wesley, Laura J. Edwards, Lauren Grant, Sara S. Kim, Suryaprakash Sambhara, Shivaprakash Gangappa, Terrence Tumpey, Mark G. Thompson, Alicia M. Fry, Brendan Flannery, Fatimah S. Dawood and Min Z. Levine ()
Additional contact information
Feng Liu: Influenza Division, Centers for Disease Control and Prevention
F. Liaini Gross: Influenza Division, Centers for Disease Control and Prevention
Sneha Joshi: Influenza Division, Centers for Disease Control and Prevention
Manjusha Gaglani: Baylor Scott & White Health
Allison L. Naleway: Kaiser Permanente Northwest Center for Health Research
Kempapura Murthy: Texas A & M University, College of Medicine
Holly C. Groom: Kaiser Permanente Northwest Center for Health Research
Meredith G. Wesley: Influenza Division, Centers for Disease Control and Prevention
Laura J. Edwards: Abt Associates
Lauren Grant: Influenza Division, Centers for Disease Control and Prevention
Sara S. Kim: Influenza Division, Centers for Disease Control and Prevention
Suryaprakash Sambhara: Influenza Division, Centers for Disease Control and Prevention
Shivaprakash Gangappa: Influenza Division, Centers for Disease Control and Prevention
Terrence Tumpey: Influenza Division, Centers for Disease Control and Prevention
Mark G. Thompson: Influenza Division, Centers for Disease Control and Prevention
Alicia M. Fry: Influenza Division, Centers for Disease Control and Prevention
Brendan Flannery: Influenza Division, Centers for Disease Control and Prevention
Fatimah S. Dawood: Influenza Division, Centers for Disease Control and Prevention
Min Z. Levine: Influenza Division, Centers for Disease Control and Prevention

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-023-44551-x

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