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

Autor: Lobaina Y; Research Department, China-Cuba Biotechnology Joint Innovation Center (CCBJIC) Lengshuitan District, Yongzhou City, 425000, Hunan, China.; R&D Department, Yongzhou Zhong Gu Biotechnology Co., Ltd., Yangjiaqiao Street, Lengshuitan District, Yongzhou City, 425000, Hunan, China., Musacchio A; Research Department, China-Cuba Biotechnology Joint Innovation Center (CCBJIC) Lengshuitan District, Yongzhou City, 425000, Hunan, China.; R&D Department, Yongzhou Zhong Gu Biotechnology Co., Ltd., Yangjiaqiao Street, Lengshuitan District, Yongzhou City, 425000, Hunan, China.; Research Department, Center for Genetic Engineering and Biotechnology (CIGB), 10600, Havana, Cuba., Ai P; Research Department, China-Cuba Biotechnology Joint Innovation Center (CCBJIC) Lengshuitan District, Yongzhou City, 425000, Hunan, China.; Yongzhou Development and Construction Investment Co. Ltd. (YDCI), Yongzhou Economic and Technological Development Zone, Changfeng Industry Park, No. 1 Liebao Road, Lengshuitan District, Yongzhou City, Hunan Province, China., Chen R; Research Department, China-Cuba Biotechnology Joint Innovation Center (CCBJIC) Lengshuitan District, Yongzhou City, 425000, Hunan, China.; Yongzhou Development and Construction Investment Co. Ltd. (YDCI), Yongzhou Economic and Technological Development Zone, Changfeng Industry Park, No. 1 Liebao Road, Lengshuitan District, Yongzhou City, Hunan Province, China., Suzarte E; Research Department, Center for Genetic Engineering and Biotechnology (CIGB), 10600, Havana, Cuba., Chinea G; Research Department, Center for Genetic Engineering and Biotechnology (CIGB), 10600, Havana, Cuba., Zhang M; Hunan PRIMA Drug Research Center Co., Ltd., National Liuyang Economic and Technological Development Zone, 123 Kangtian Road, Changsha City, Hunan, China., Zhou Z; Hunan PRIMA Drug Research Center Co., Ltd., National Liuyang Economic and Technological Development Zone, 123 Kangtian Road, Changsha City, Hunan, China., Lan Y; Research Department, China-Cuba Biotechnology Joint Innovation Center (CCBJIC) Lengshuitan District, Yongzhou City, 425000, Hunan, China.; Yongzhou Development and Construction Investment Co. Ltd. (YDCI), Yongzhou Economic and Technological Development Zone, Changfeng Industry Park, No. 1 Liebao Road, Lengshuitan District, Yongzhou City, Hunan Province, China., Silva R; Science and Innovation Directorate, BioCubaFarma, Independence Avenue, No. 8126, Corner 100 Street, 10800, Havana, Cuba., Guillén G; Research Department, Center for Genetic Engineering and Biotechnology (CIGB), 10600, Havana, Cuba., Yang K; Research Department, China-Cuba Biotechnology Joint Innovation Center (CCBJIC) Lengshuitan District, Yongzhou City, 425000, Hunan, China.; Yongzhou Development and Construction Investment Co. Ltd. (YDCI), Yongzhou Economic and Technological Development Zone, Changfeng Industry Park, No. 1 Liebao Road, Lengshuitan District, Yongzhou City, Hunan Province, China., Li W; Research Department, China-Cuba Biotechnology Joint Innovation Center (CCBJIC) Lengshuitan District, Yongzhou City, 425000, Hunan, China. liwen@ccbjic.com.; Yongzhou Development and Construction Investment Co. Ltd. (YDCI), Yongzhou Economic and Technological Development Zone, Changfeng Industry Park, No. 1 Liebao Road, Lengshuitan District, Yongzhou City, Hunan Province, China. liwen@ccbjic.com., Perera Y; Research Department, China-Cuba Biotechnology Joint Innovation Center (CCBJIC) Lengshuitan District, Yongzhou City, 425000, Hunan, China. ypereranegrin@ccbjic.com.; R&D Department, Yongzhou Zhong Gu Biotechnology Co., Ltd., Yangjiaqiao Street, Lengshuitan District, Yongzhou City, 425000, Hunan, China. ypereranegrin@ccbjic.com.; Research Department, Center for Genetic Engineering and Biotechnology (CIGB), 10600, Havana, Cuba. ypereranegrin@ccbjic.com., Hermida L; Research Department, China-Cuba Biotechnology Joint Innovation Center (CCBJIC) Lengshuitan District, Yongzhou City, 425000, Hunan, China. lhermida@oc.biocubafarma.cu.; Yongzhou Development and Construction Investment Co. Ltd. (YDCI), Yongzhou Economic and Technological Development Zone, Changfeng Industry Park, No. 1 Liebao Road, Lengshuitan District, Yongzhou City, Hunan Province, China. lhermida@oc.biocubafarma.cu.; Science and Innovation Directorate, BioCubaFarma, Independence Avenue, No. 8126, Corner 100 Street, 10800, Havana, Cuba. lhermida@oc.biocubafarma.cu.
Jazyk: angličtina
Zdroj: Virology journal [Virol J] 2024 Nov 29; Vol. 21 (1), pp. 310. Date of Electronic Publication: 2024 Nov 29.
DOI: 10.1186/s12985-024-02583-9
Abstrakt: 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.
Competing Interests: Declarations. Ethical approval and consent to participate: The human sera from COVID-19 convalescent and negative individuals were collected at the Eighth- and Ninth-People’s Hospital of Dongguan city (Guangdong Province, China). The study protocol was approved by the Institutional Ethics Committee from both hospitals and was carried out in accordance with the principles of Helsinki declaration. Informed consent was obtained from all donors. Human and animal rights: The studies in mice were conducted at Beijing Vital River Laboratory Animal Technology Co., Ltd, and Hunan Prima Drug Research Center Co., Ltd. Both animal facilities complied with the national standard of the People's Republic of China GB14925-2010 and the institutional guidelines. Each experimental protocol was subjected to analysis and approval by the Institutional Ethics Committee (Protocols: PANCOV04 approved on 12.04.2022, and HNSE2023(3)012 approved on 20.02.2023). In all the studies inhaled isoflurane, at regular dose or overdose, was employed as anesthesia or euthanasia method, respectively. Competing interests: Y. Lobaina, A.M., P.A., R.C., E.S., Y. Lan, G.C., R.S., G.G, K.Y, Y.P., L.H., are authors of a patent (recently presented in China) related to the content of the manuscript.
(© 2024. The Author(s).)
Databáze: MEDLINE
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