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

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

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.