Site-Specific and Stable Conjugation of the SARS-CoV‑2 Receptor-Binding Domain to Liposomes in the Absence of Any Other Adjuvants Elicits Potent Neutralizing Antibodies in BALB/c Mice

• Published in: Bioconjugate chemistry 2021-12, Vol.32 (12), p.2497-2506
• Main Authors: Wholey, Wei-Yun, Yoda, Sekou-Tidiane, Cheng, Wei
• Format: Article
• Language: English
• Subjects: Adjuvants; Adjuvants, Immunologic - chemistry; Adjuvants, Immunologic - therapeutic use; Animals; Antibodies; Antibodies, Neutralizing - immunology; Binding; Conjugation; Coronaviruses; COVID-19; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 Vaccines - chemistry; COVID-19 Vaccines - therapeutic use; Domains; Encapsulation; Female; HIV; Human immunodeficiency virus; Humans; Immunization; Infections; Liposomes; Liposomes - chemistry; Liposomes - therapeutic use; Mice; Mice, Inbred BALB C; Models, Molecular; mRNA Vaccines - chemistry; mRNA Vaccines - therapeutic use; Pandemics; Protein Domains; Proteins; Public health; Receptors; Respiratory diseases; SARS-CoV-2 - immunology; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - therapeutic use; Vaccines, Synthetic - chemistry; Vaccines, Synthetic - therapeutic use; Viral diseases; Viral infections; Virions
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/acs.bioconjchem.1c00463

Understanding immune responses toward viral infection will be useful for potential therapeutic intervention and offer insights into the design of prophylactic vaccines. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic. To understand the complex immune responses toward SARS-CoV-2 infection, here we developed a method to express and purify the recombinant and engineered viral receptor-binding domain (RBD) to more than 95% purity. We could encapsulate RNA molecules into the interior of a virion-sized liposome. We conjugated the purified RBD proteins onto the surface of the liposome in an orientation-specific manner with defined spatial densities. Both the encapsulation of RNAs and the chemical conjugation of the RBD protein on liposome surfaces were stable under physiologically relevant conditions. In contrast to soluble RBD proteins, a single injection of RBD-conjugated liposomes alone, in the absence of any other adjuvants, elicited RBD-specific B cell responses in BALB/c mice, and the resulting animal sera could potently neutralize HIV-1 pseudovirions that displayed the SARS-CoV-2 spike proteins. These results validate these supramolecular structures as a novel and effective tool to mimic the structure of enveloped viruses, the use of which will allow systematic dissection of the complex B cell responses to SARS-CoV-2 infection.