Development of nanoparticle vaccines utilizing designed Fc-binding homo-oligomers and RBD-Fc of SARS-CoV-2

• Published in: Antiviral research Vol. 227; p. 105917
• Main Authors: Liang, Yucai, Xiao, Weiling, Peng, Yuan, Zhang, Shengshuo, Dong, Jinhua, Zhao, Jun, Wang, Yuhui, Zhang, Mengtao, Liu, Zhijun, Yu, Bowen
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2024
• Subjects: Animals; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 Vaccines - immunology; Designed Fc-binding homo-oligomer; Female; Humans; Immunity, Cellular; Immunogenicity, Vaccine; Immunoglobulin Fc Fragments - chemistry; Immunoglobulin Fc Fragments - immunology; Mice; Mice, Inbred BALB C; Nanoparticle vaccines; Nanoparticles - chemistry; Nanovaccines; Protein Binding; Protein Multimerization; RBD-Fc; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology; SARS-CoV-2; SARS-CoV-2 - immunology; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - immunology; Vaccine Development; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - chemistry; Vaccines, Synthetic - immunology; RBD-Fc; Nanoparticle vaccines; SARS-CoV-2; Designed Fc-binding homo-oligomer
• ISSN: 0166-3542; 1872-9096; 1872-9096
• DOI: 10.1016/j.antiviral.2024.105917

The Fc-fused receptor binding domain (RBD-Fc) vaccine for SARS-CoV-2 has garnered significant attention for its capacity to provide effective and specific immune protection. However, its immunogenicity is limited, highlighting the need for improvement in clinical application. Nanoparticle delivery has been shown to be an effective method for enhancing antigen immunogenicity. In this study, we developed bivalent nanoparticle recombinant protein vaccines by assembling the RBD-Fc of SARS-CoV-2 and Fc-binding homo-oligomers o42.1 and i52.3 into octahedral and icosahedral nanoparticles. The formation of RBD-Fc nanoparticles was confirmed through structural characterization and cell binding experiments. Compared to RBD-Fc dimers, the nanoparticle vaccines induced more potent neutralizing antibodies (nAb) and stronger cellular immune responses. Therefore, using bivalent nanoparticle vaccines based on RBD-Fc presents a promising vaccination strategy against SARS-CoV-2 and offers a universal approach for enhancing the immunogenicity of Fc fusion protein vaccines. •RBD-Fc based nanoparticle vaccines are assembled using designed Fc-binding homo-oligomers.•RBD-Fc nanoparticle vaccines enhance the humoral and cellular immune response induced by RBD-Fc.•This study provides a feasible method for enhancing the immunogenicity of Fc fusion antigens.