Nanoparticle display of neuraminidase elicits enhanced antibody responses and protection against influenza A virus challenge

M N Pascha; M Ballegeer; M C Roelofs; L Meuris; I C Albulescu; F J M van Kuppeveld; D L Hurdiss; B J Bosch; T Zeev-Ben-Mordehai; X Saelens; C A M de Haan

doi:10.1038/s41541-024-00891-3

Nanoparticle display of neuraminidase elicits enhanced antibody responses and protection against influenza A virus challenge

M N Pascha, M Ballegeer, M C Roelofs, L Meuris, I C Albulescu, F J M van Kuppeveld, D L Hurdiss, B J Bosch, T Zeev-Ben-Mordehai, X Saelens^*, C A M de Haan^*

^*Corresponding author for this work

VIB Center for Medical Biotechnology

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Current Influenza virus vaccines primarily induce antibody responses against variable epitopes in hemagglutinin (HA), necessitating frequent updates. However, antibodies against neuraminidase (NA) can also confer protection against influenza, making NA an attractive target for the development of novel vaccines. In this study, we aimed to enhance the immunogenicity of recombinant NA antigens by presenting them multivalently on a nanoparticle carrier. Soluble tetrameric NA antigens of the N1 and N2 subtypes, confirmed to be correctly folded by cryo-electron microscopy structural analysis, were conjugated to Mi3 self-assembling protein nanoparticles using the SpyTag-SpyCatcher system. Immunization of mice with NA-Mi3 nanoparticles induced higher titers of NA-binding and -inhibiting antibodies and improved protection against a lethal challenge compared to unconjugated NA. Additionally, we explored the co-presentation of N1 and N2 antigens on the same Mi3 particles to create a mosaic vaccine candidate. These mosaic nanoparticles elicited antibody titers that were similar or superior to the homotypic nanoparticles and effectively protected against H1N1 and H3N2 challenge viruses. The NA-Mi3 nanoparticles represent a promising vaccine candidate that could complement HA-directed approaches for enhanced potency and broadened protection against influenza A virus.

Original language	English
Article number	97
Number of pages	14
Journal	npj Vaccines
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41541-024-00891-3
Publication status	Published - 31 May 2024

Bibliographical note

Publisher Copyright:
© The Author(s) 2024.

Funding

This study was done within the framework of the research program of the Netherlands Centre for One Health (www.ncoh.nl) and co-funded by the PPP Allowance made available by Health~Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships. This work was supported in part by the ENDFLU project that has received funding from the European Union\u2019s Horizon 2020 research and innovation program under Grant agreement No. 874650. The authors would like to thank Tony Smits and Laura Blekkenhorst for technical assistance with recombinant protein expression and MUNANA assays.

Funders	Funder number
Health~Holland, Top Sector Life Sciences & Health
Horizon 2020 Framework Programme	874650
Horizon 2020 Framework Programme

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Pascha, M. N., Ballegeer, M., Roelofs, M. C., Meuris, L., Albulescu, I. C., van Kuppeveld, F. J. M., Hurdiss, D. L., Bosch, B. J., Zeev-Ben-Mordehai, T., Saelens, X., & de Haan, C. A. M. (2024). Nanoparticle display of neuraminidase elicits enhanced antibody responses and protection against influenza A virus challenge. npj Vaccines, 9(1), Article 97. https://doi.org/10.1038/s41541-024-00891-3

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Nanoparticle display of neuraminidase elicits enhanced antibody responses and protection against influenza A virus challenge

Abstract

Bibliographical note

Funding

UN SDGs

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