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Research Article

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

Ming Xia1,§Md Rejaul Hoq2,§Pengwei Huang1,§Wen Jiang2Xi Jiang1,3Ming Tan1,3( )
Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
Department of Biological Sciences, Purdue Cryo-EM Facility, Purdue University, IN 47907, USA
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA

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

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Graphical Abstract

A new technology has been developed to generate unique S60-HA1 pseudovirus nanoparticles (PVNPs) that display the receptor-binding HA1 antigens of influenza viruses (IVs). These PVNPs offer new reagents for IV study and provide a promising flu vaccine candidate to fight the deadly influenza.

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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Nano Research
Pages 4181-4190
Cite this article:
Xia M, Hoq MR, Huang P, et al. Bioengineered pseudovirus nanoparticles displaying the HA1 antigens of influenza viruses for enhanced immunogenicity. Nano Research, 2022, 15(5): 4181-4190. https://doi.org/10.1007/s12274-021-4011-x
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Received: 03 October 2021
Revised: 19 November 2021
Accepted: 22 November 2021
Published: 28 January 2022
© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2021
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