Nanoparticle Vaccines Based on the Receptor Binding Domain (RBD) and Heptad Repeat (HR) of SARS-CoV-2 Elicit Robust Protective Immune Responses

• Published in: Immunity Vol. 53; no. 6; pp. 1315 - 1330.e9
• Main Authors: Ma, Xiancai, Zou, Fan, Yu, Fei, Li, Rong, Yuan, Yaochang, Zhang, Yiwen, Zhang, Xiantao, Deng, Jieyi, Chen, Tao, Song, Zheng, Qiao, Yidan, Zhan, Yikang, Liu, Jun, Zhang, Junsong, Zhang, Xu, Peng, Zhilin, Li, Yuzhuang, Lin, Yingtong, Liang, Liting, Wang, Guanwen, Chen, Yingshi, Chen, Qier, Pan, Ting, He, Xin, Zhang, Hui
• Format: Journal Article Web Resource
• Language: English
• Published: United States Elsevier Inc 15.12.2020; Elsevier BV; Elsevier Limited
• Subjects: Adenoviruses; Angiotensin-Converting Enzyme 2 - genetics; Angiotensin-Converting Enzyme 2 - metabolism; Animals; Antibodies; Antibodies, Neutralizing - metabolism; Antibodies, Viral - metabolism; Antigens; Bacterial Proteins - chemistry; Bacterial Proteins - immunology; Binding; Clinical trials; Coronaviridae; Coronaviruses; COVID-19; COVID-19 - immunology; COVID-19 Vaccines - chemistry; COVID-19 Vaccines - immunology; Domains; Enzymes; Ferritin; Ferritins - chemistry; Ferritins - immunology; Helicobacter pylori - metabolism; Humans; Immune response (cell-mediated); Immunization; Infections; Influenza; Lymphocytes; Macaca mulatta; Mice; Mice, Inbred BALB C; Middle East respiratory syndrome; nanoparticle vaccine; Nanoparticles; Nanoparticles - chemistry; Neutralizing; Pandemics; Protein Binding; Proteins; RBD; Receptors; Recombinant Fusion Proteins - immunology; Robustness; SARS-CoV-2; SARS-CoV-2 - physiology; Self-assembly; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - immunology; Transgenic mice; Vaccination; Vaccines; Viral diseases; COVID-19; SARS-CoV-2; HR; nanoparticle vaccine; RBD
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2020.11.015

Various vaccine strategies have been proposed in response to the global COVID-19 pandemic, each with unique strategies for eliciting immune responses. Here, we developed nanoparticle vaccines by covalently conjugating the self-assembled 24-mer ferritin to the receptor binding domain (RBD) and/or heptad repeat (HR) subunits of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) spike (S) protein. Compared to monomer vaccines, nanoparticle vaccines elicited more robust neutralizing antibodies and cellular immune responses. RBD and RBD-HR nanoparticle vaccinated hACE2 transgenic mice vaccinated with RBD and/or RBD-HR nanoparticles exhibited reduced viral load in the lungs after SARS-CoV-2 challenge. RBD-HR nanoparticle vaccines also promoted neutralizing antibodies and cellular immune responses against other coronaviruses. The nanoparticle vaccination of rhesus macaques induced neutralizing antibodies, and T and B cell responses prior to boost immunization; these responses persisted for more than three months. RBD- and HR-based nanoparticles thus present a promising vaccination approach against SARS-CoV-2 and other coronaviruses. [Display omitted] •RBD and HR nanoparticle vaccines induce potent neutralizing antibody responses•Nanoparticle vaccines protect against SARS-CoV-2 infection in mice•HR antigens elicit both humoral and cellular immune responses•HR antigens within nanoparticles contribute to cross-protective immunity Ma et al. construct two Ferritin-based nanoparticle vaccines that conjugate RBD and HR antigens in SARS-CoV-2 Spike protein utilizing the SpyTag/SpyCatcher system. RBD and RBD-HR nanoparticles vaccines elicit more potent neutralizing antibody responses and stronger T cell immune responses than monomers. HR-containing nanoparticles induce cross-reactive immune responses against other coronaviruses.