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Open Access 01-12-2024 | Research

Obtaining HBV core protein VLPs carrying SARS-CoV-2 nucleocapsid conserved fragments as vaccine candidates

Authors: Yadira Lobaina, Alexis Musacchio, Panchao Ai, Rong Chen, Edith Suzarte, Glay Chinea, Miaohong Zhang, Zhiqiang Zhou, Yaqin Lan, Ricardo Silva, Gerardo Guillén, Ke Yang, Wen Li, Yasser Perera, Lisset Hermida

Published in: Virology Journal | Issue 1/2024

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.

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Title: Obtaining HBV core protein VLPs carrying SARS-CoV-2 nucleocapsid conserved fragments as vaccine candidates
Authors: Yadira Lobaina
Alexis Musacchio
Panchao Ai
Rong Chen
Edith Suzarte
Glay Chinea
Miaohong Zhang
Zhiqiang Zhou
Yaqin Lan
Ricardo Silva
Gerardo Guillén
Ke Yang
Wen Li
Yasser Perera
Lisset Hermida
Publication date: 01-12-2024
Publisher: BioMed Central
Published in: Virology Journal / Issue 1/2024
Electronic ISSN: 1743-422X
DOI: https://doi.org/10.1186/s12985-024-02583-9

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