tetano
Editor, Senior Moderator
Virol J
. 2024 Nov 29;21(1):310.
doi: 10.1186/s12985-024-02583-9. Obtaining HBV core protein VLPs carrying SARS-CoV-2 nucleocapsid conserved fragments as vaccine candidates
Yadira Lobaina[SUP] 1 2 [/SUP], Alexis Musacchio[SUP] 1 2 3 [/SUP], Panchao Ai[SUP] 1 4 [/SUP], Rong Chen[SUP] 1 4 [/SUP], Edith Suzarte[SUP] 3 [/SUP], Glay Chinea[SUP] 3 [/SUP], Miaohong Zhang[SUP] 5 [/SUP], Zhiqiang Zhou[SUP] 5 [/SUP], Yaqin Lan[SUP] 1 4 [/SUP], Ricardo Silva[SUP] 6 [/SUP], Gerardo Guillén[SUP] 3 [/SUP], Ke Yang[SUP] 1 4 [/SUP], Wen Li[SUP] 7 8 [/SUP], Yasser Perera[SUP] 9 10 11 [/SUP], Lisset Hermida[SUP] 12 13 14 [/SUP]
Affiliations
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.
Keywords: Chimeric proteins; HBcAg; Intranasal; Nucleocapsid; Pancorona vaccine; SARS-CoV-2.
. 2024 Nov 29;21(1):310.
doi: 10.1186/s12985-024-02583-9. Obtaining HBV core protein VLPs carrying SARS-CoV-2 nucleocapsid conserved fragments as vaccine candidates
Yadira Lobaina[SUP] 1 2 [/SUP], Alexis Musacchio[SUP] 1 2 3 [/SUP], Panchao Ai[SUP] 1 4 [/SUP], Rong Chen[SUP] 1 4 [/SUP], Edith Suzarte[SUP] 3 [/SUP], Glay Chinea[SUP] 3 [/SUP], Miaohong Zhang[SUP] 5 [/SUP], Zhiqiang Zhou[SUP] 5 [/SUP], Yaqin Lan[SUP] 1 4 [/SUP], Ricardo Silva[SUP] 6 [/SUP], Gerardo Guillén[SUP] 3 [/SUP], Ke Yang[SUP] 1 4 [/SUP], Wen Li[SUP] 7 8 [/SUP], Yasser Perera[SUP] 9 10 11 [/SUP], Lisset Hermida[SUP] 12 13 14 [/SUP]
Affiliations
- PMID: 39609857
- PMCID: PMC11606075
- DOI: 10.1186/s12985-024-02583-9
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.
Keywords: Chimeric proteins; HBcAg; Intranasal; Nucleocapsid; Pancorona vaccine; SARS-CoV-2.