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Peer-reviewedCC BY-NC-ND 4.0NPJ Vaccines

Hemagglutination-inhibition and microneutralization antibody titers as mediators of protection for cell-based and recombinant influenza vaccines

  • Shuyi Zhong1
  • Wey Wen Lim1
  • Faith Ho1
  • Manjusha Gaglani2,3,4
  • Allison L. Naleway4
  • Fatimah S. Dawood5
  • Min Z. Levine5
  • Kelsey Sumner5
  • Brendan Flannery5
  • Benjamin J. Cowling1
5 affiliations
  1. 1School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region, China
  2. 2Baylor Scott & White Health, Temple, TX USA
  3. 3Baylor College of Medicine, Temple, TX USA
  4. 4Kaiser Permanente Center for Health Research, Portland, OR USA
  5. 5Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA USA
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Abstract

The proportion of relative influenza vaccine efficacy (rVE) mediated by post-vaccination hemagglutination inhibition (HAI) and microneutralization (MN) antibody titers has not been evaluated. We compared rVE by influenza vaccine type and HAI and MN antibody titer against symptomatic influenza A(H3N2) infection in a randomized immunogenicity trial of quadrivalent cell culture-based (ccIIV4), recombinant (RIV4), and egg-based (eIIV4) influenza vaccines in US healthcare personnel, and estimated proportions of rVE mediated by antibody titers using causal mediation analysis. Cumulative influenza A(H3N2) incidence was 3.2%, 1.3% and 1% among ccIIV, eIIV4 and RIV4 recipients, respectively. Age-adjusted rVE estimates were not statistically significant. Higher MN and HAI titers against A(H3N2) vaccine and circulating viruses explained 97.9% and 15.8%, respectively, of rVE for RIV4 compared with ccIIV4, versus 1.7% and 12.6% of rVE for eIIV4 compared with ccIIV4, indicating MN titers to be used as correlates of protection against A(H3N2) for comparisons between cell-based influenza vaccines.

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Cite

BibTeXRIS
BibTeX
@article{zhong2026hemagglutinationinhibition,
  title = {{Hemagglutination-inhibition and microneutralization antibody titers as mediators of protection for cell-based and recombinant influenza vaccines}},
  author = {Shuyi Zhong and Wey Wen Lim and Faith Ho and Manjusha Gaglani and Allison L. Naleway and Fatimah S. Dawood and Min Z. Levine and Kelsey Sumner and Brendan Flannery and Benjamin J. Cowling},
  journal = {NPJ Vaccines},
  year = {2026},
  month = jul,
  doi = {10.1038/s41541-026-01521-w},
  url = {https://doi.org/10.1038/s41541-026-01521-w},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Hemagglutination-inhibition and microneutralization antibody titers as mediators of protection for cell-based and recombinant influenza vaccines
AU  - Shuyi Zhong
AU  - Wey Wen Lim
AU  - Faith Ho
AU  - Manjusha Gaglani
AU  - Allison L. Naleway
AU  - Fatimah S. Dawood
AU  - Min Z. Levine
AU  - Kelsey Sumner
AU  - Brendan Flannery
AU  - Benjamin J. Cowling
PY  - 2026
DA  - 2026/07/09
JO  - NPJ Vaccines
DO  - 10.1038/s41541-026-01521-w
UR  - https://doi.org/10.1038/s41541-026-01521-w
AB  - The proportion of relative influenza vaccine efficacy (rVE) mediated by post-vaccination hemagglutination inhibition (HAI) and microneutralization (MN) antibody titers has not been evaluated. We compared rVE by influenza vaccine type and HAI and MN antibody titer against symptomatic influenza A(H3N2) infection in a randomized immunogenicity trial of quadrivalent cell culture-based (ccIIV4), recombinant (RIV4), and egg-based (eIIV4) influenza vaccines in US healthcare personnel, and estimated proportions of rVE mediated by antibody titers using causal mediation analysis. Cumulative influenza A(H3N2) incidence was 3.2%, 1.3% and 1% among ccIIV, eIIV4 and RIV4 recipients, respectively. Age-adjusted rVE estimates were not statistically significant. Higher MN and HAI titers against A(H3N2) vaccine and circulating viruses explained 97.9% and 15.8%, respectively, of rVE for RIV4 compared with ccIIV4, versus 1.7% and 12.6% of rVE for eIIV4 compared with ccIIV4, indicating MN titers to be used as correlates of protection against A(H3N2) for comparisons between cell-based influenza vaccines.
SN  - 2059-0105
ER  -