Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates

So Hee Hong; Hanseul Oh; Yong Wook Park; Hye Won Kwak; Eun Young Oh; Hyo Jung Park; Kyung Won Kang; Green Kim; Bon Sang Koo; Eun Ha Hwang; Seung Ho Baek; Hyeong Jun Park; Yu Sun Lee; Yoo Jin Bang; Jae Yong Kim; Seo Hyeon Bae; Su Jeen Lee; Ki Weon Seo; Hak Kim; Taewoo Kwon; Ji Hwan Kim; Seonghwan Lee; Eunsom Kim; Yeonhwa Kim; Jae Hak Park; Sang In Park; Marta Gonçalves; Byung Mook Weon; Haengdueng Jeong; Ki Taek Nam; Kyung Ah Hwang; Jihye Kim; Hun Kim; Sang Myeong Lee; Jung Joo Hong; Jae Hwan Nam

doi:10.1126/sciadv.abg7156

Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates

So Hee Hong, Hanseul Oh, Yong Wook Park, Hye Won Kwak, Eun Young Oh, Hyo Jung Park, Kyung Won Kang, Green Kim, Bon Sang Koo, Eun Ha Hwang, Seung Ho Baek, Hyeong Jun Park, Yu Sun Lee, Yoo Jin Bang, Jae Yong Kim, Seo Hyeon Bae, Su Jeen Lee, Ki Weon Seo, Hak Kim, Taewoo KwonJi Hwan Kim, Seonghwan Lee, Eunsom Kim, Yeonhwa Kim, Jae Hak Park, Sang In Park, Marta Gonçalves, Byung Mook Weon, Haengdueng Jeong, Ki Taek Nam, Kyung Ah Hwang, Jihye Kim, Hun Kim, Sang Myeong Lee, Jung Joo Hong, Jae Hwan Nam

Department of Microbiology

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

20 Scopus citations

Abstract

Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), various vaccines are being developed, with most vaccine candidates focusing on the viral spike protein. Here, we developed a previously unknown subunit vaccine comprising the receptor binding domain (RBD) of the spike protein fused with the tetanus toxoid epitope P2 (RBD-P2) and tested its efficacy in rodents and nonhuman primates (NHPs). We also investigated whether the SARS-CoV-2 nucleocapsid protein (N) could increase vaccine efficacy. Immunization with N and RBD-P2 (RBDP2/N) + alum increased T cell responses in mice and neutralizing antibody levels in rats compared with those obtained using RBD-P2 + alum. Furthermore, in NHPs, RBD-P2/N + alum induced slightly faster SARS-CoV-2 clearance than that induced by RBD-P2 + alum, albeit without statistical significance. Our study supports further development of RBD-P2 as a vaccine candidate against SARS-CoV-2. Also, it provides insights regarding the use of N in protein-based vaccines against SARS-CoV-2.

Original language	English
Article number	eabg7156
Journal	Science Advances
Volume	7
Issue number	22
DOIs	https://doi.org/10.1126/sciadv.abg7156
State	Published - May 2021

Bibliographical note

Funding Information:
This work was supported by grants from RIGHT and SK Bioscience (grant nos. M-2020-D0731-0002 and M-2020-D0732-0003), as well as by the Ministry of Science and ICT and the Korea Research Institute of Bioscience (PRM1752011), Bio-industrial Core Technology Development Project from the Ministry of Trade, Industry, and Energy (20013101) and Biotechnology (KRIBB) Research Initiative Program (KGM4572013).

Publisher Copyright:
Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).

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Hong, S. H., Oh, H., Park, Y. W., Kwak, H. W., Oh, E. Y., Park, H. J., Kang, K. W., Kim, G., Koo, B. S., Hwang, E. H., Baek, S. H., Park, H. J., Lee, Y. S., Bang, Y. J., Kim, J. Y., Bae, S. H., Lee, S. J., Seo, K. W., Kim, H., ... Nam, J. H. (2021). Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates. Science Advances, 7(22), Article eabg7156. https://doi.org/10.1126/sciadv.abg7156

@article{0427ed083c9346ad91f7259b0e335be2,

title = "Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates",

abstract = "Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), various vaccines are being developed, with most vaccine candidates focusing on the viral spike protein. Here, we developed a previously unknown subunit vaccine comprising the receptor binding domain (RBD) of the spike protein fused with the tetanus toxoid epitope P2 (RBD-P2) and tested its efficacy in rodents and nonhuman primates (NHPs). We also investigated whether the SARS-CoV-2 nucleocapsid protein (N) could increase vaccine efficacy. Immunization with N and RBD-P2 (RBDP2/N) + alum increased T cell responses in mice and neutralizing antibody levels in rats compared with those obtained using RBD-P2 + alum. Furthermore, in NHPs, RBD-P2/N + alum induced slightly faster SARS-CoV-2 clearance than that induced by RBD-P2 + alum, albeit without statistical significance. Our study supports further development of RBD-P2 as a vaccine candidate against SARS-CoV-2. Also, it provides insights regarding the use of N in protein-based vaccines against SARS-CoV-2.",

author = "Hong, {So Hee} and Hanseul Oh and Park, {Yong Wook} and Kwak, {Hye Won} and Oh, {Eun Young} and Park, {Hyo Jung} and Kang, {Kyung Won} and Green Kim and Koo, {Bon Sang} and Hwang, {Eun Ha} and Baek, {Seung Ho} and Park, {Hyeong Jun} and Lee, {Yu Sun} and Bang, {Yoo Jin} and Kim, {Jae Yong} and Bae, {Seo Hyeon} and Lee, {Su Jeen} and Seo, {Ki Weon} and Hak Kim and Taewoo Kwon and Kim, {Ji Hwan} and Seonghwan Lee and Eunsom Kim and Yeonhwa Kim and Park, {Jae Hak} and Park, {Sang In} and Marta Gon{\c c}alves and Weon, {Byung Mook} and Haengdueng Jeong and Nam, {Ki Taek} and Hwang, {Kyung Ah} and Jihye Kim and Hun Kim and Lee, {Sang Myeong} and Hong, {Jung Joo} and Nam, {Jae Hwan}",

note = "Funding Information: This work was supported by grants from RIGHT and SK Bioscience (grant nos. M-2020-D0731-0002 and M-2020-D0732-0003), as well as by the Ministry of Science and ICT and the Korea Research Institute of Bioscience (PRM1752011), Bio-industrial Core Technology Development Project from the Ministry of Trade, Industry, and Energy (20013101) and Biotechnology (KRIBB) Research Initiative Program (KGM4572013). Publisher Copyright: Copyright {\textcopyright} 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).",

year = "2021",

month = may,

doi = "10.1126/sciadv.abg7156",

language = "English",

volume = "7",

journal = "Science Advances",

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publisher = "American Association for the Advancement of Science",

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Hong, SH, Oh, H, Park, YW, Kwak, HW, Oh, EY, Park, HJ, Kang, KW, Kim, G, Koo, BS, Hwang, EH, Baek, SH, Park, HJ, Lee, YS, Bang, YJ, Kim, JY, Bae, SH, Lee, SJ, Seo, KW, Kim, H, Kwon, T, Kim, JH, Lee, S, Kim, E, Kim, Y, Park, JH, Park, SI, Gonçalves, M, Weon, BM, Jeong, H, Nam, KT, Hwang, KA, Kim, J, Kim, H, Lee, SM, Hong, JJ & Nam, JH 2021, 'Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates', Science Advances, vol. 7, no. 22, eabg7156. https://doi.org/10.1126/sciadv.abg7156

TY - JOUR

T1 - Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates

AU - Hong, So Hee

AU - Oh, Hanseul

AU - Park, Yong Wook

AU - Kwak, Hye Won

AU - Oh, Eun Young

AU - Park, Hyo Jung

AU - Kang, Kyung Won

AU - Kim, Green

AU - Koo, Bon Sang

AU - Hwang, Eun Ha

AU - Baek, Seung Ho

AU - Park, Hyeong Jun

AU - Lee, Yu Sun

AU - Bang, Yoo Jin

AU - Kim, Jae Yong

AU - Bae, Seo Hyeon

AU - Lee, Su Jeen

AU - Seo, Ki Weon

AU - Kim, Hak

AU - Kwon, Taewoo

AU - Kim, Ji Hwan

AU - Lee, Seonghwan

AU - Kim, Eunsom

AU - Kim, Yeonhwa

AU - Park, Jae Hak

AU - Park, Sang In

AU - Gonçalves, Marta

AU - Weon, Byung Mook

AU - Jeong, Haengdueng

AU - Nam, Ki Taek

AU - Hwang, Kyung Ah

AU - Kim, Jihye

AU - Kim, Hun

AU - Lee, Sang Myeong

AU - Hong, Jung Joo

AU - Nam, Jae Hwan

N1 - Funding Information: This work was supported by grants from RIGHT and SK Bioscience (grant nos. M-2020-D0731-0002 and M-2020-D0732-0003), as well as by the Ministry of Science and ICT and the Korea Research Institute of Bioscience (PRM1752011), Bio-industrial Core Technology Development Project from the Ministry of Trade, Industry, and Energy (20013101) and Biotechnology (KRIBB) Research Initiative Program (KGM4572013). Publisher Copyright: Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).

PY - 2021/5

Y1 - 2021/5

N2 - Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), various vaccines are being developed, with most vaccine candidates focusing on the viral spike protein. Here, we developed a previously unknown subunit vaccine comprising the receptor binding domain (RBD) of the spike protein fused with the tetanus toxoid epitope P2 (RBD-P2) and tested its efficacy in rodents and nonhuman primates (NHPs). We also investigated whether the SARS-CoV-2 nucleocapsid protein (N) could increase vaccine efficacy. Immunization with N and RBD-P2 (RBDP2/N) + alum increased T cell responses in mice and neutralizing antibody levels in rats compared with those obtained using RBD-P2 + alum. Furthermore, in NHPs, RBD-P2/N + alum induced slightly faster SARS-CoV-2 clearance than that induced by RBD-P2 + alum, albeit without statistical significance. Our study supports further development of RBD-P2 as a vaccine candidate against SARS-CoV-2. Also, it provides insights regarding the use of N in protein-based vaccines against SARS-CoV-2.

AB - Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), various vaccines are being developed, with most vaccine candidates focusing on the viral spike protein. Here, we developed a previously unknown subunit vaccine comprising the receptor binding domain (RBD) of the spike protein fused with the tetanus toxoid epitope P2 (RBD-P2) and tested its efficacy in rodents and nonhuman primates (NHPs). We also investigated whether the SARS-CoV-2 nucleocapsid protein (N) could increase vaccine efficacy. Immunization with N and RBD-P2 (RBDP2/N) + alum increased T cell responses in mice and neutralizing antibody levels in rats compared with those obtained using RBD-P2 + alum. Furthermore, in NHPs, RBD-P2/N + alum induced slightly faster SARS-CoV-2 clearance than that induced by RBD-P2 + alum, albeit without statistical significance. Our study supports further development of RBD-P2 as a vaccine candidate against SARS-CoV-2. Also, it provides insights regarding the use of N in protein-based vaccines against SARS-CoV-2.

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DO - 10.1126/sciadv.abg7156

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AN - SCOPUS:85106973854

SN - 2375-2548

VL - 7

JO - Science Advances

JF - Science Advances

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ER -

Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates

Abstract

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