Comparison of neuraminidase inhibiting antibody responses elicited by egg- and cell-derived influenza vaccines

Esmeralda Alvarado-Facundo; Rachel Herrup; Wei Wang; Rhonda E Colombo; Limone Collins; Anuradha Ganesan; David Hrncir; Tahaniyat Lalani; Ana Elizabeth Markelz; Ryan C Maves; Bruce McClenathan; Katrin Mende; Stephanie A Richard; Kat Schmidt; Christina Schofield; Srihari Seshadri; Christina Spooner; Christian L Coles; Timothy H Burgess; Carol D Weiss; Maryna Eichelberger

doi:10.1016/j.vaccine.2024.126669

Comparison of neuraminidase inhibiting antibody responses elicited by egg- and cell-derived influenza vaccines

Vaccine. 2025 Jan 3:46:126669. doi: 10.1016/j.vaccine.2024.126669. Online ahead of print.

Authors

Esmeralda Alvarado-Facundo¹, Rachel Herrup¹, Wei Wang¹, Rhonda E Colombo², Limone Collins³, Anuradha Ganesan⁴, David Hrncir³, Tahaniyat Lalani⁵, Ana Elizabeth Markelz⁶, Ryan C Maves⁷, Bruce McClenathan³, Katrin Mende⁸, Stephanie A Richard⁹, Kat Schmidt⁹, Christina Schofield¹⁰, Srihari Seshadri³, Christina Spooner³, Christian L Coles⁹, Timothy H Burgess¹¹, Carol D Weiss¹, Maryna Eichelberger¹²

Affiliations

¹ Center for Biologics Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
² Infectious Diseases Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA; Madigan Army Medical Center, Tacoma, WA, USA; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
³ Immunization Healthcare Division, Defense Health Agency, Bethesda, MD, Falls Church, VA, Fort Liberty, NC, and San Diego, CA, USA.
⁴ Infectious Diseases Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA; Walter Reed National Military Medical Center, Bethesda, MD, USA.
⁵ Infectious Diseases Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA; Naval Medical Center Portsmouth, Portsmouth, VA, USA.
⁶ Brooke Army Medical Center, San Antonio, TX, USA.
⁷ Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Naval Medical Center San Diego, San Diego, CA, USA; Wake Forest University School of Medicine, Winston-Salem, NC, USA.
⁸ Infectious Diseases Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA; Brooke Army Medical Center, San Antonio, TX, USA.
⁹ Infectious Diseases Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA.
¹⁰ Madigan Army Medical Center, Tacoma, WA, USA; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
¹¹ Infectious Diseases Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
¹² Center for Biologics Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA. Electronic address: [email protected].

PMID: 39754936
DOI: 10.1016/j.vaccine.2024.126669

Abstract

Neuraminidase (NA)-specific antibodies contribute to immunity against influenza. While studies have demonstrated increased NA inhibiting (NAI) antibody titers after vaccination with egg-derived inactivated influenza vaccines (eIIV), the response to cell culture-derived (c) IIV has not been reported.

Methods: An immunogenicity sub-study was performed within a clinical trial comparing the effectiveness of egg, cell, and recombinant hemagglutinin (HA)-derived influenza vaccines during the 2018-2019 and 2019-2020 influenza seasons. NAI and neutralizing antibody titers against the A(H1N1)pdm09 and A(H3N2) components of the vaccines were measured in pre- and post-vaccination sera.

Results: Responses to the N1 component of eIIV and cIIV were different in both study years 1 and 2 whereas response rate and antibody titers to the N2 component of egg and cell culture-derived vaccines were similar. For example, 43.5 % of eIIV and no cIIV recipients had four-fold NAI titer increases in year 1. There was a weak positive correlation between responses to N1 and N2 for both vaccine types but no correlation between NAI and HA-specific neutralizing antibody responses. Recombinant HA vaccine that does not contain NA served as a specificity control; NAI antibody titers did not increase in recipients except in two individuals presumed to have subclinical infection.

Conclusion: Antibody responses to NA following vaccination with eIIV and cIIV were not the same; although the responses to the N1 and N2 components of eIIV were similar, there were fewer responders to N1 than N2 of cIIV. Studies to determine the impact of NA immunity on influenza vaccine effectiveness are warranted.

Keywords: Antibody titers; Egg- and cell-derived vaccines; Influenza vaccine; Neuraminidase; Recombinant hemagglutinin vaccine.

Published by Elsevier Ltd.