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. 2022 Jan 28;15(5):4181–4190. doi: 10.1007/s12274-021-4011-x

Bioengineered pseudovirus nanoparticles displaying the HA1 antigens of influenza viruses for enhanced immunogenicity

Ming Xia 1,#, Md Rejaul Hoq 2,#, Pengwei Huang 1,#, Wen Jiang 2, Xi Jiang 1,3, Ming Tan 1,3,✉
PMCID: PMC8795936  PMID: 35106126

Abstract

Even with implementation of current influenza vaccines, influenza still claims up to 500,000 lives worldwide annually, indicating a need for a better vaccine strategy. We have developed a technology to generate unique S60-HA1 pseudovirus nanoparticles (PVNPs) that display the receptor-binding HA1 domains of influenza viruses. Each self-assembled S60-HA1 PVNP consists of a T = 1 icosahedral S60 nanoparticle that resembles the inner shell of norovirus capsid and 60 surface-displayed HA1 antigens that are excellent vaccine targets. Soluble S60-HA1 PVNPs presenting HA1 antigens of H7N9 influenza virus subtypes have been produced efficiently in large amount. Their three-dimensional (3D) structures have been solved by cryogenic electron microscopy. The PVNP-displayed HA1 antigens react with HA-specific antibody, and retain authentic sialic acid binding specificity and hemagglutinate human erythrocytes. The PVNPs are highly immunogenic, eliciting high titers of HA1-specific antibodies in mice and the mouse sera strongly inhibited hemagglutinations of homologous and heterologous influenza virus HA proteins. Therefore, the S60-HA1 PVNPs may provide useful reagents to study influenza viruses and offer a potential new vaccine tactic to fight the deadly influenza disease.

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Keywords: S60 nanoparticle, pseudovirus nanoparticle, influenza virus, influenza vaccine, hemagglutinin, norovirus

Acknowledgment

The research described in this study was supported by the National Institute of Allergy and Infectious Diseases (NIAID, No. R56 AI148426-01A1 to M.T.), Cincinnati Children Hospital Medical Center (CCHMC, Innovation Funds 2018–2020, GAP Fund 2020–2021, and Research Innovation and Pilot Grant 2020–2021 to M.T.), and the Center for Clinical and Translational Science and Training (CCTST) of the University of Cincinnati College of Medicine (Pilot Collaborative Studies Grant 2018–2019 to M.T.) that was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (No. UL1TR001425). We thank the Purdue Cryo-EM Facility (http://cryoem.bio.purdue.edu) for help in the 3D structure reconstruction of the PVNPs.

Footnotes

Ming Xia, Md Rejaul Hoq, and Pengwei Huang contributed equally to this work.

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