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MF59-adjuvanted A/Astrakhan influenza vaccine induces cross-neutralizing H5N1 antibodies in ferrets against circulating clade 2.3.4.4b viruses
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  • Published: 06 April 2026

MF59-adjuvanted A/Astrakhan influenza vaccine induces cross-neutralizing H5N1 antibodies in ferrets against circulating clade 2.3.4.4b viruses

  • Karen Segovia1 na1,
  • Raveen Rathnasinghe1 na1,
  • Christopher Patton1,
  • Byungjoon Kwon1,
  • Ray A. Longstaff2,
  • Dirk Hofmann3,
  • Kulwinder K. Banger4,
  • Howard Xu1,
  • Marc Lacey2,
  • Ethan Settembre1,
  • Giuseppe Palladino1,
  • Alexander T. Kennedy2 &
  • …
  • Nedzad Music1 

npj Vaccines , Article number:  (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Diseases
  • Immunology
  • Microbiology

Abstract

The continued global spread of highly pathogenic avian influenza A(H5N1) viruses, particularly clade 2.3.4.4b, has increased zoonotic spillover risk and underscored the urgency of pandemic preparedness. Human vaccination is a key strategy for mitigating severe disease and limiting transmission, especially in a setting where avian influenza viruses pose a zoonotic threat. We evaluated the immunogenicity of the MF59-adjuvanted, egg-derived A/Astrakhan/3212/2020 (H5N8) influenza vaccine (CBER-RG8A) in ferrets. To assess cross-reactivity, we generated pseudoviruses bearing HA and NA from circulating A(H5N1) 2.3.4.4b viruses, including North American (B1.13 and D1.1) and Eurasian (DI.2) genotypes. Immunogenicity was assessed using hemagglutination inhibition and microneutralization assays. A single dose elicited robust neutralizing titers (GMT ≥ 160), while a second dose increased titers by ≥3.3-fold. Cross-reactivity was maintained across most strains; however, responses were reduced up to 8-fold against strains harboring the A156T HA mutation, which may introduce a glycosylation site at antigenic site B. Limited responses were detected against divergent clades, with modest titers against clade 2.3.2.1a. These findings suggest broad protection induced by the CSL Seqirus pandemic vaccine against contemporary clade 2.3.4.4b A(H5N1) viruses and underscore the value of ferret immunogenicity data in informing strain selection and regulatory preparedness when human clinical data are unavailable.

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Data availability

The datasets generated and/or analyzed during the current study are not publicly available due to sponsor data sharing policies that restrict public release outside a controlled access process, but are available from the corresponding authors on reasonable request, subject to an appropriate data sharing agreement with the sponsor.

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Acknowledgements

This study and the associated publication costs were funded by Seqirus USA Inc. Editorial support for manuscript preparation was provided by Charlie Knox and Jamie Stirling (Seqirus Medical Publication and Communication team).

Author information

Author notes

  1. These authors contributed equally: Karen Segovia, Raveen Rathnasinghe.

Authors and Affiliations

  1. CSL Seqirus, Waltham, MA, USA

    Karen Segovia, Raveen Rathnasinghe, Christopher Patton, Byungjoon Kwon, Howard Xu, Ethan Settembre, Giuseppe Palladino & Nedzad Music

  2. CSL Seqirus, Maidenhead, UK

    Ray A. Longstaff, Marc Lacey & Alexander T. Kennedy

  3. CSL Seqirus, Basel, Switzerland

    Dirk Hofmann

  4. CSL Seqirus, Liverpool, UK

    Kulwinder K. Banger

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  1. Karen Segovia
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Contributions

Conceptualization: K.S., R.R., E.S., G.P., A.T.K., and N.M.; Methodology: K.S., R.R., E.S., G.P., A.T.K., and N.M.; Investigation: K.S., R.R., C.P., B.K., R.A.L., D.H., K.K.B., H.X., M.L., E.S., G.P., A.T.K., and N.M.; Writing original draft: K.S., R.R., and N.M.; Writing review & editing: K.S., R.R., C.P., B.K., R.A.L., D.H., K.K.B.,. H.X., M.L., E.S., G.P., A.T.K., and N.M.

Corresponding authors

Correspondence to Alexander T. Kennedy or Nedzad Music.

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All authors were permanently employed by the CSL Seqirus group of companies at the time the work described in this paper was performed. Some authors own CSL stocks.

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Segovia, K., Rathnasinghe, R., Patton, C. et al. MF59-adjuvanted A/Astrakhan influenza vaccine induces cross-neutralizing H5N1 antibodies in ferrets against circulating clade 2.3.4.4b viruses. npj Vaccines (2026). https://doi.org/10.1038/s41541-026-01438-4

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  • Received: 24 November 2025

  • Accepted: 26 March 2026

  • Published: 06 April 2026

  • DOI: https://doi.org/10.1038/s41541-026-01438-4

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