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Monoglycosylated SARS-CoV-2 receptor binding domain fused with HAstem-scaffolded protein vaccine confers broad protective immunity against SARS-CoV-2 and influenza viruses.
Wu, Chia-Ying; Tseng, Yung-Chieh; Kao, Shao-En; Wu, Li-Yang; Hou, Jen-Tzu; Yang, Yu-Chih; Hsiao, Pei-Wen; Chen, Juine-Ruey.
Afiliação
  • Wu CY; RuenHuei Biopharmaceuticals Inc. Taipei, Taiwan.
  • Tseng YC; RuenHuei Biopharmaceuticals Inc. Taipei, Taiwan.
  • Kao SE; RuenHuei Biopharmaceuticals Inc. Taipei, Taiwan.
  • Wu LY; RuenHuei Biopharmaceuticals Inc. Taipei, Taiwan.
  • Hou JT; RuenHuei Biopharmaceuticals Inc. Taipei, Taiwan.
  • Yang YC; Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
  • Hsiao PW; Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
  • Chen JR; RuenHuei Biopharmaceuticals Inc. Taipei, Taiwan. Electronic address: jrchen@rhbiopharma.com.
Antiviral Res ; 220: 105759, 2023 12.
Article em En | MEDLINE | ID: mdl-37984568
The SARS-CoV-2 and influenza pandemics have posed a devastating threat to global public health. The best strategy for preventing the further spread of these respiratory viruses worldwide is to administer a vaccine capable of targeting both viruses. Here, we show that a novel monoglycosylated vaccine designed based on the influenza virus HAstem conserved domain fused with the SARS-CoV-2 spike-RBD domain (HSSRmg) can present proper antigenicity that elicits sufficient neutralization efficacy against various SARS-CoV-2 variants while simultaneously providing broad protection against H1N1 viruses in mice. Compared with the fully glycosylated HSSR (HSSRfg), HSSRmg induced higher ELISA titers targeting HAstem and spike-RBD and exhibited significantly enhanced neutralization activity against the Wuhan pseudovirus. The enhanced immune responses raised by JR300-adjuvanted HSSRmg compared to HSSRmg alone include more anti-HAstem and anti-spike-RBD antibodies that provide cross-protection against H1N1 challenges and cross-neutralization of SARS-CoV-2 pseudoviruses. Furthermore, the enhanced immune response raised by JR300-adjuvanted-HSSRmg skews toward a more balanced Th1/Th2 response than that raised by HSSRmg alone. Notably, HSSRmg elicited more plasma B cells and memory B cells, and higher IL-4 and IFN-γ cytokine immune responses than spike (S-2P) in mice with preexisting influenza-specific immunity, suggesting that B-cell activation most likely occurs through CD4+ T-cell stimulation. This study demonstrated that HSSRmg produced using a monoglycosylation process and combined with the JR300 adjuvant elicits superior cross-strain immune responses against SARS-CoV-2 and influenza viruses in mice compared with S-2P. JR300-adjuvanted HSSRmg has great potential as a coronavirus-influenza vaccine that provides dual protection against SARS-CoV-2 and influenza infections.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vacinas Virais / Influenza Humana / Vírus da Influenza A Subtipo H1N1 / COVID-19 Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vacinas Virais / Influenza Humana / Vírus da Influenza A Subtipo H1N1 / COVID-19 Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article