Novel virus-like nanoparticle vaccine effectively protects animal model from SARS-CoV-2 infection

Qibin Geng; Wanbo Tai; Victoria K. Baxter; Juan Shi; Yushun Wan; Xiujuan Zhang; Stephanie A. Montgomery; Sharon A. Taft-Benz; Elizabeth J. Anderson; Audrey C. Knight; Kenneth H. Dinnon; Sarah R. Leist; Ralph S. Baric; Jian Shang; Sung Wook Hong; Aleksandra Drelich; Chien Te K. Tseng; Marc Jenkins; Mark Heise; Lanying Du; Fang Li

doi:10.1371/journal.ppat.1009897

Novel virus-like nanoparticle vaccine effectively protects animal model from SARS-CoV-2 infection

Qibin Geng, Wanbo Tai, Victoria K. Baxter, Juan Shi, Yushun Wan, Xiujuan Zhang, Stephanie A. Montgomery, Sharon A. Taft-Benz, Elizabeth J. Anderson, Audrey C. Knight, Kenneth H. Dinnon, Sarah R. Leist, Ralph S. Baric, Jian Shang, Sung Wook Hong, Aleksandra Drelich, Chien Te K. Tseng, Marc Jenkins, Mark Heise, Lanying DuFang Li

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Abstract

The key to battling the COVID-19 pandemic and its potential aftermath is to develop a variety of vaccines that are efficacious and safe, elicit lasting immunity, and cover a range of SARS-CoV-2 variants. Recombinant viral receptor-binding domains (RBDs) are safe vaccine candidates but often have limited efficacy due to the lack of virus-like immunogen display pattern. Here we have developed a novel virus-like nanoparticle (VLP) vaccine that displays 120 copies of SARS-CoV-2 RBD on its surface. This VLP-RBD vaccine mimics virus-based vaccines in immunogen display, which boosts its efficacy, while maintaining the safety of protein-based subunit vaccines. Compared to the RBD vaccine, the VLP-RBD vaccine induced five times more neutralizing antibodies in mice that efficiently blocked SARS-CoV-2 from attaching to its host receptor and potently neutralized the cell entry of variant SARS-CoV-2 strains, SARS-CoV-1, and SARS-CoV-1-related bat coronavirus. These neutralizing immune responses induced by the VLP-RBD vaccine did not wane during the two-month study period. Furthermore, the VLP-RBD vaccine effectively protected mice from SARS-CoV-2 challenge, dramatically reducing the development of clinical signs and pathological changes in immunized mice. The VLP-RBD vaccine provides one potentially effective solution to controlling the spread of SARS-CoV-2.

Original language	English (US)
Article number	e1009897
Journal	PLoS pathogens
Volume	17
Issue number	9
DOIs	https://doi.org/10.1371/journal.ppat.1009897
State	Published - Sep 7 2021

Bibliographical note

Funding Information:
Funding: This study was supported by funding from the University of Minnesota (to F.L.), NIH grants R01AI139092 (to F.L. and L.D.), R01AI089728 (to F.L. and R.S.B.), R01 AI110700 and U01 AI149644 (to R.S.B.), R01AI157253 (to M.H and RSB), and K01OD026529 (to V.K.B). K.H. D. III. was supported by T32AI007419 and A.C.K. was supported by T32AI007151.

Publisher Copyright:
Copyright: © 2021 Geng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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

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10.1371/journal.ppat.1009897

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Geng, Q., Tai, W., Baxter, V. K., Shi, J., Wan, Y., Zhang, X., Montgomery, S. A., Taft-Benz, S. A., Anderson, E. J., Knight, A. C., Dinnon, K. H., Leist, S. R., Baric, R. S., Shang, J., Hong, S. W., Drelich, A., Tseng, C. T. K., Jenkins, M., Heise, M., ... Li, F. (2021). Novel virus-like nanoparticle vaccine effectively protects animal model from SARS-CoV-2 infection. PLoS pathogens, 17(9), Article e1009897. https://doi.org/10.1371/journal.ppat.1009897

Geng, Q, Tai, W, Baxter, VK, Shi, J, Wan, Y, Zhang, X, Montgomery, SA, Taft-Benz, SA, Anderson, EJ, Knight, AC, Dinnon, KH, Leist, SR, Baric, RS, Shang, J, Hong, SW, Drelich, A, Tseng, CTK, Jenkins, M, Heise, M, Du, L & Li, F 2021, 'Novel virus-like nanoparticle vaccine effectively protects animal model from SARS-CoV-2 infection', PLoS pathogens, vol. 17, no. 9, e1009897. https://doi.org/10.1371/journal.ppat.1009897

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abstract = "The key to battling the COVID-19 pandemic and its potential aftermath is to develop a variety of vaccines that are efficacious and safe, elicit lasting immunity, and cover a range of SARS-CoV-2 variants. Recombinant viral receptor-binding domains (RBDs) are safe vaccine candidates but often have limited efficacy due to the lack of virus-like immunogen display pattern. Here we have developed a novel virus-like nanoparticle (VLP) vaccine that displays 120 copies of SARS-CoV-2 RBD on its surface. This VLP-RBD vaccine mimics virus-based vaccines in immunogen display, which boosts its efficacy, while maintaining the safety of protein-based subunit vaccines. Compared to the RBD vaccine, the VLP-RBD vaccine induced five times more neutralizing antibodies in mice that efficiently blocked SARS-CoV-2 from attaching to its host receptor and potently neutralized the cell entry of variant SARS-CoV-2 strains, SARS-CoV-1, and SARS-CoV-1-related bat coronavirus. These neutralizing immune responses induced by the VLP-RBD vaccine did not wane during the two-month study period. Furthermore, the VLP-RBD vaccine effectively protected mice from SARS-CoV-2 challenge, dramatically reducing the development of clinical signs and pathological changes in immunized mice. The VLP-RBD vaccine provides one potentially effective solution to controlling the spread of SARS-CoV-2.",

author = "Qibin Geng and Wanbo Tai and Baxter, {Victoria K.} and Juan Shi and Yushun Wan and Xiujuan Zhang and Montgomery, {Stephanie A.} and Taft-Benz, {Sharon A.} and Anderson, {Elizabeth J.} and Knight, {Audrey C.} and Dinnon, {Kenneth H.} and Leist, {Sarah R.} and Baric, {Ralph S.} and Jian Shang and Hong, {Sung Wook} and Aleksandra Drelich and Tseng, {Chien Te K.} and Marc Jenkins and Mark Heise and Lanying Du and Fang Li",

note = "Funding Information: Funding: This study was supported by funding from the University of Minnesota (to F.L.), NIH grants R01AI139092 (to F.L. and L.D.), R01AI089728 (to F.L. and R.S.B.), R01 AI110700 and U01 AI149644 (to R.S.B.), R01AI157253 (to M.H and RSB), and K01OD026529 (to V.K.B). K.H. D. III. was supported by T32AI007419 and A.C.K. was supported by T32AI007151. Publisher Copyright: Copyright: {\textcopyright} 2021 Geng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

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AU - Du, Lanying

AU - Li, Fang

N1 - Funding Information: Funding: This study was supported by funding from the University of Minnesota (to F.L.), NIH grants R01AI139092 (to F.L. and L.D.), R01AI089728 (to F.L. and R.S.B.), R01 AI110700 and U01 AI149644 (to R.S.B.), R01AI157253 (to M.H and RSB), and K01OD026529 (to V.K.B). K.H. D. III. was supported by T32AI007419 and A.C.K. was supported by T32AI007151. Publisher Copyright: Copyright: © 2021 Geng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Novel virus-like nanoparticle vaccine effectively protects animal model from SARS-CoV-2 infection

Abstract

Bibliographical note

UN SDGs

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