A vaccine targeting the RBD of the S protein of SARS-CoV-2 induces protective immunity

Yang, Jingyun; Wang, Wei; Chen, Zimin; Lu, Shuaiyao; Yang, Fulun; Bi, Zhenfei; Bao, Linlin; Mo, Fei; Li, Xue; Huang, Yong; Hong, Weiqi; Yang, Yun; Zhao, Yuan; Ye, Fei; Lin, Sheng; Deng, Wei; Chen, Hua; Hong, Lei; Zhang, Ziqi; Luo, Min; Gao, Hong; Zheng, Yue; Gong, Yanqiu; Jiang, Xiaohua; Xu, Yanfeng; Lv, Qi; Li, Dan; Wang, Manni; Li, Fengdi; Wang, Shunyi; Wang, Guanpeng; Yü, Ping; Qu, Yajin; Yang, Li; Deng, Hongxin; Tong, Aiping; Li, Jiong; Wang, Zhenling; Yang, Jinliang; Shen, Guobo; Zhao, Zhiwei; Li, Yuhua; Luo, Jingwen; Liu, Hongqi; Wu, Yu; Yang, Mengli; Xu, Jingwen; Wang, Junbin; Li, Haiyan; Wang, Haixuan; Kuang, Dexuan; Lin, Panpan; Hu, Zhengtao; Guo, Wei; Cheng, Wei; He, Yanlin; Song, Xiangrong; Chen, Chong; Xue, Zhihong; Yao, Su; Chen, Lu; Ma, Xuelei; Chen, Siyuan; Gou, Maling; Huang, Weijin; Wang, Youchun; Fan, Chen; Tian, Zhixin; Shi, Ming; Wang, Fu Sheng; Dai, Lunzhi; Wu, Min; Li, Gen; Wang, Guangyu; Peng, Yong; Qian, Zhiyong; Huang, Canhua; Lau, Johnson Yiu Nam; Yang, Zhenglin; Wei, Yuquan; Cen, Xiaobo; Qin, Chuan; Zhang, Kang; Lu, Guangwen; Wei, Xiawei

doi:10.1038/s41586-020-2599-8

Cited by 705 publications

(762 citation statements)

References 36 publications

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“…Multiple studies employing a variety of vaccine formulations and modalities have now demonstrated that SARS-CoV-2 viral neutralization titers in small animals including mice and guinea pigs are predictive of immunogenicity in macaques and humans ( Figure 5E) [17][18][19][20]22,23,[33][34][35][36][37][40][41][42][43]45 . Despite promising immunogenicity in several cases, all of the above liquid formulations were either refrigerated or frozen prior to use.…”

Section: Discussionmentioning

confidence: 99%

Design of a highly thermotolerant, immunogenic SARS-CoV-2 spike fragment immunogen

Malladi

Singh

Pandey

et al. 2020

Preprint

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Virtually all SARS-CoV-2 vaccines currently in clinical testing are stored in a refrigerated or frozen state prior to use. This is a major impediment to deployment in resource-poor settings. Several use viral vectors or mRNA. In contrast to protein subunit vaccines, there is limited manufacturing expertise for these novel, nucleic acid based modalities, especially in the developing world. Neutralizing antibodies, the clearest known correlate of protection against SARS-CoV-2, are primarily directed against the Receptor Binding Domain (RBD) of the viral spike protein. We describe a monomeric, glycan engineered RBD protein fragment that is expressed at a purified yield of 200mg/L in unoptimized, mammalian cell culture and in contrast to a stabilized spike ectodomain, is tolerant of exposure to temperatures as high as 100°C when lyophilized, and upto 70°C in solution. In prime:boost guinea pig immunizations, when formulated with the MF59 like adjuvant AddaVax™, the RBD derivative elicited neutralizing antibodies with an endpoint geometric mean titer of ~415 against replicative virus, comparing favourably with several vaccine formulations currently in the clinic. These features of high yield, extreme thermotolerance and satisfactory immunogenicity suggest that such RBD subunit vaccine formulations hold great promise to combat COVID-19.

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Section: Discussionmentioning

confidence: 99%

Design of a highly thermotolerant, immunogenic SARS-CoV-2 spike fragment immunogen

Malladi

Singh

Pandey

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Zhang N et al have also demonstrated that an LNP-encapsulated SARS-CoV-2 RBD-based mRNA vaccine (ARCoV) is able to induce in mice and NHPs both neutralizing antibody response and Th1biased cellular response, resulting in full protection against challenge of a mouse-adapted SARS-CoV-2 strain 40 . More recently, Yang J et al have demonstrated that RBD-based COVID-19 vaccine could induce much higher titer of neutralizing antibody (NT50: ~2,400) than S protein (NT50: ~300) and S1 subunit (NT50: ~1,100) 41 . Moreover, a disul de-linked SARS-CoV-2 RBD dimer was demonstrated to enhance the neutralizing antibody titer compared to the RBD monomer 36 .…”

Section: Discussionmentioning

confidence: 99%

The recombinant subunit vaccine RBD-Fc, consisting of SARS-CoV-2 RBD and human IgG Fc as an immunopotentiator, elicits robust neutralizing antibody responses against SARS-CoV-2 infection

Liu

Xia

et al. 2020

Preprint

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The pandemic of COVID-19 caused by SARS-CoV-2 has posed serious threats to global health and economy, thus calling for the development of safe and effective vaccines. The receptor-binding domain (RBD) in the spike protein of SARS-CoV-2 is responsible for its binding to ACE2 receptor. It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines. Here, we showed that immunization of mice with a candidate subunit vaccine consisting of SARS-CoV-2 RBD and Fc fragment of human IgG, as an immunopotentiator, elicited high titer of RBD-specific antibodies with robust neutralizing activity against both pseudotyped and live SARS-CoV-2 infections. The mouse antisera could also effectively neutralize infection by pseudotyped SARS-CoV-2 with several natural mutations in RBD and the IgG extracted from the mouse antisera could also show neutralization against pseudotyped SARS-CoV and SARS-related coronavirus (SARSr-CoV). Vaccination of human ACE2 transgenic mice with RBD-Fc could effectively protect mice from the SARS-CoV-2 challenge. These results suggest that SARS-CoV-2 RBD-Fc has good potential to be further developed as an effective and broad-spectrum vaccine to prevent infection of the current SARS-CoV-2 and its mutants, as well as future emerging SARSr-CoVs and re-emerging SARS-CoV.

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“…Several recent reports on vaccines using RBD exhibited high neutralization and protection against the infection 7,25 . Although even monomeric RBD protein produced a response 7 , it was substantially stronger against the dimeric RBD 25 . Here we provide a comparison of four different types of genetically encoded scaffolds fused to the RBD and implemented as DNA vaccines.…”

Section: Immune Response Against the Scaffold In A Genetic Fusion Witmentioning

confidence: 97%

“…An effective vaccine should trigger formation of a protective humoral and cell mediated immune response against the viral components that will either inhibit viral entry and replication or kill virus-infected cells. Different vaccination platforms for the presentation of viral components have been used, including inactivated or attenuated viral particles, purified proteins, mRNA, plasmid DNA, nonreplicating viruses; each of them with particular features [4][5][6][7][8][9] . The advantages of DNA plasmid delivery including the speed of adaptation to new targets, cost effective production, stability at ambient temperature without the need for a cold chain make it a potentially attractive vaccination platform, although no DNA plasmid vaccine has been approved for humans so far 10,11 .…”

Section: Introductionmentioning

confidence: 99%

Immune response to vaccine candidates based on different types of nanoscaffolded RBD domain of the SARS-CoV-2 spike protein

Fink

Forstnerič

Hafner-Bratkovič

et al. 2020

Preprint

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Effective and safe vaccines against SARS-CoV-2 are highly desirable to prevent casualties and societal cost caused by Covid-19 pandemic. The receptor binding domain (RBD) of the surface-exposed spike protein of SARS-CoV-2 represents a suitable target for the induction of neutralizing antibodies upon vaccination. Small protein antigens typically induce weak immune response while particles measuring tens of nanometers are efficiently presented to B cell follicles and subsequently to follicular germinal center B cells in draining lymph nodes, where B cell proliferation and affinity maturation occurs. Here we prepared and analyzed the response to several DNA vaccines based on genetic fusions of RBD to four different scaffolding domains, namely to the foldon peptide, ferritin, lumazine synthase and β-annulus peptide, presenting from 6 to 60 copies of the RBD on each particle. Scaffolding strongly augmented the immune response with production of neutralizing antibodies and T cell response including cytotoxic lymphocytes in mice upon immunization with DNA plasmids. The most potent response was observed for the 24-residue β-annulus peptide scaffold that forms large soluble assemblies, that has the advantage of low immunogenicity in comparison to larger scaffolds. Our results support the advancement of this vaccine platform towards clinical trials.

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A vaccine targeting the RBD of the S protein of SARS-CoV-2 induces protective immunity

Cited by 705 publications

References 36 publications

Design of a highly thermotolerant, immunogenic SARS-CoV-2 spike fragment immunogen

Design of a highly thermotolerant, immunogenic SARS-CoV-2 spike fragment immunogen

The recombinant subunit vaccine RBD-Fc, consisting of SARS-CoV-2 RBD and human IgG Fc as an immunopotentiator, elicits robust neutralizing antibody responses against SARS-CoV-2 infection

Immune response to vaccine candidates based on different types of nanoscaffolded RBD domain of the SARS-CoV-2 spike protein

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