1. Obtaining HBV core protein VLPs carrying SARS-CoV-2 nucleocapsid conserved fragments as vaccine candidates.
- Author
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Lobaina, Yadira, Musacchio, Alexis, Ai, Panchao, Chen, Rong, Suzarte, Edith, Chinea, Glay, Zhang, Miaohong, Zhou, Zhiqiang, Lan, Yaqin, Silva, Ricardo, Guillén, Gerardo, Yang, Ke, Li, Wen, Perera, Yasser, and Hermida, Lisset
- Abstract
The Hepatitis B core antigen (HBcAg) has been used as a carrier of several heterologous protein fragments based on its capacity to form virus-like particles (VLPs) and to activate innate and adaptive immune responses. In the present work, two chimeric proteins were designed as potential pancorona vaccine candidates, comprising the N- or C- terminal domain of SARS-CoV-2 nucleocapsid (N) protein fused to HBcAg. The recombinant proteins, obtained in E. coli, were named CN-1 and CND-1, respectively. The final protein preparations were able to form 10–25 nm particles, visualized by TEM. Both proteins were recognized by sera from COVID-19 convalescent donors; however, the antigenicity of CND-1 tends to be higher. The immunogenicity of both proteins was studied in Balb/C mice by intranasal route without adjuvant. After three doses, only CND-1 elicited a positive immune response, systemic and mucosal, against SARS-CoV-2 N protein. CND-1 was evaluated in a second experiment mixed with the CpG ODN-39 M as nasal adjuvant. The induced anti-N immunity was significantly enhanced, and the antibodies generated were cross-reactive with N protein from Omicron variant, and SARS-CoV-1. Also, an anti-N broad cellular immune response was detected in spleen, by IFN-γ ELISpot. The nasal formulation composed by CND-1 and ODN-39 M constitutes an attractive component for a second generation coronavirus vaccine, increasing the scope of S protein-based vaccines, by inducing mucosal immunity and systemic broad humoral and cellular responses against Sarbecovirus N protein. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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