tetano
Editor, Senior Moderator
Antiviral Res
. 2023 Nov 18:105759.
doi: 10.1016/j.antiviral.2023.105759. Online ahead of print. Monoglycosylated SARS-CoV-2 receptor binding domain fused with HA[SUB]stem[/SUB]-scaffolded protein vaccine confers broad protective immunity against SARS-CoV-2 and influenza viruses
Chia-Ying Wu[SUP] 1 [/SUP], Yung-Chieh Tseng[SUP] 1 [/SUP], Shao-En Kao[SUP] 1 [/SUP], Li-Yang Wu[SUP] 1 [/SUP], Jen-Tzu Hou[SUP] 1 [/SUP], Yu-Chih Yang[SUP] 2 [/SUP], Pei-Wen Hsiao[SUP] 2 [/SUP], Juine-Ruey Chen[SUP] 3 [/SUP]
Affiliations
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 HA[SUB]stem[/SUB] conserved domain fused with the SARS-CoV-2 spike-RBD domain (HSSR[SUB]mg[/SUB]) 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 (HSSR[SUB]fg[/SUB]), HSSR[SUB]mg[/SUB] induced higher ELISA titers targeting HA[SUB]stem[/SUB] and spike-RBD and exhibited significantly enhanced neutralization activity against the Wuhan pseudovirus. The enhanced immune responses raised by JR300-adjuvanted HSSR[SUB]mg[/SUB] compared to HSSR[SUB]mg[/SUB] alone include more anti-HA[SUB]stem[/SUB] 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-HSSR[SUB]mg[/SUB] skews toward a more balanced Th1/Th2 response than that raised by HSSR[SUB]mg[/SUB] alone. Notably, HSSR[SUB]mg[/SUB] 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[SUP]+[/SUP] T-cell stimulation. This study demonstrated that HSSR[SUB]mg[/SUB] 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 HSSR[SUB]mg[/SUB] has great potential as a coronavirus-influenza vaccine that provides dual protection against SARS-CoV-2 and influenza infections.
. 2023 Nov 18:105759.
doi: 10.1016/j.antiviral.2023.105759. Online ahead of print. Monoglycosylated SARS-CoV-2 receptor binding domain fused with HA[SUB]stem[/SUB]-scaffolded protein vaccine confers broad protective immunity against SARS-CoV-2 and influenza viruses
Chia-Ying Wu[SUP] 1 [/SUP], Yung-Chieh Tseng[SUP] 1 [/SUP], Shao-En Kao[SUP] 1 [/SUP], Li-Yang Wu[SUP] 1 [/SUP], Jen-Tzu Hou[SUP] 1 [/SUP], Yu-Chih Yang[SUP] 2 [/SUP], Pei-Wen Hsiao[SUP] 2 [/SUP], Juine-Ruey Chen[SUP] 3 [/SUP]
Affiliations
- PMID: 37984568
- DOI: 10.1016/j.antiviral.2023.105759
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 HA[SUB]stem[/SUB] conserved domain fused with the SARS-CoV-2 spike-RBD domain (HSSR[SUB]mg[/SUB]) 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 (HSSR[SUB]fg[/SUB]), HSSR[SUB]mg[/SUB] induced higher ELISA titers targeting HA[SUB]stem[/SUB] and spike-RBD and exhibited significantly enhanced neutralization activity against the Wuhan pseudovirus. The enhanced immune responses raised by JR300-adjuvanted HSSR[SUB]mg[/SUB] compared to HSSR[SUB]mg[/SUB] alone include more anti-HA[SUB]stem[/SUB] 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-HSSR[SUB]mg[/SUB] skews toward a more balanced Th1/Th2 response than that raised by HSSR[SUB]mg[/SUB] alone. Notably, HSSR[SUB]mg[/SUB] 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[SUP]+[/SUP] T-cell stimulation. This study demonstrated that HSSR[SUB]mg[/SUB] 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 HSSR[SUB]mg[/SUB] has great potential as a coronavirus-influenza vaccine that provides dual protection against SARS-CoV-2 and influenza infections.