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Journal of General Virology header logo Journal of General Virology

Volume 107, Issue 3

Immunogenicity of SARS-CoV-2 vaccine prototype based on virus-like particles of hepatitis B core antigen from genotype G and interleukin 12 expressing Semliki Forest virus as a genetic adjuvant Open Access

Abstract

Virus-like particles (VLPs) based on hepatitis B core antigen (HBc) represent an immunogenic and modular platform for epitope presentation. In this study, the VLPs formed by the modified recombinant hepatitis B core antigen from genotype G (HBc/G) were used as carriers for the presentation of a receptor-binding motif (RBM) of the Delta variant of Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). The RBM was inserted at the C-terminus of the modified HBc/G extended by the addition of a second, specifically modified C-terminal domain of HBc/G. All arginine residues in the extra domain were replaced with glycine, resulting in a ‘two-tailed’ HBc/G-Gly vector. The resulting HBc/G-Gly-RBM construct successfully formed regular VLPs in and elicited specific antibody responses in mice. Despite the moderate immunogenicity of the RBM insert compared with the HBc carrier, sera from RBM-VLP-immunized animals exhibited neutralizing activity against MLV particles pseudotyped with the SARS-CoV-2 Delta spike and showed cross-reactivity with receptor-binding domains from the Wuhan and Omicron variants. To enhance the immune response, a replication-deficient Semliki Forest virus (SFV) vector expressing IL-12 was evaluated alone and in combination with the squalene-based adjuvant AddaVax. The co-administration of SFV-IL12 and AddaVax modestly improved virus neutralization rates and promoted a Th1 response, characterized by increased IgG2a production and IFN- secretion. These findings demonstrate the feasibility of combining classical and genetic adjuvants with the HBc-based VLP platform and provide preliminary insights for further optimization toward more potent and protective SARS-CoV-2 vaccine candidates.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): C-terminal domain , core protein , hepatitis B virus , IL-12 as adjuvant , immunogenicity , SARS-CoV-2 RBM , Semliki Forest virus and virus-like particles
Funding
This study was supported by the:
  • Latvijas Zinātnes Padome (Award lzp-2021/1-0059)
    • Principal Award Recipient: IrinaSominskaya
© 2026 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2026-03-05
2026-04-13

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Immunogenicity of SARS-CoV-2 vaccine prototype based on virus-like particles of hepatitis B core antigen from genotype G and interleukin 12 expressing Semliki Forest virus as a genetic adjuvant
J. Gen. Virol. 107, 002240 (2026); https://doi.org/10.1099/jgv.0.002240
/content/journal/jgv/10.1099/jgv.0.002240
/content/journal/jgv/10.1099/jgv.0.002240
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