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Low-Dose SARS-CoV-2 S-Trimer with an Emulsion Adjuvant Induced Th1-Biased Protective Immunity
Hung-Chun Liao1,2, Wan-Ling Wu1, Chen-Yi Chiang1
1National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, Taiwan.
International Journal of Molecular Sciences
|May 14, 2022
Summary
A novel recombinant spike (S)-Trimer vaccine, when combined with the SWE adjuvant, demonstrated superior immunogenicity and protective efficacy against SARS-CoV-2 in preclinical models. This combination offers a promising strategy for developing effective COVID-19 vaccines.
Area of Science:
- Vaccinology
- Immunology
- Virology
Background:
- Global mass vaccination is crucial for controlling the COVID-19 pandemic and preventing viral mutations.
- An ideal protein subunit vaccine should be safe, effective, stable, easily manufactured, and require minimal storage.
- Recombinant spike (S)-Trimer vaccines aim to elicit robust immune responses against SARS-CoV-2.
Purpose of the Study:
- To design and produce a prefusion-stabilized recombinant S-Trimer with high ACE2 binding affinity.
- To evaluate the immunogenicity and efficacy of the S-Trimer vaccine formulated with different adjuvants (Alum or SWE) or no adjuvant.
- To assess the potential of the SWE adjuvant for dose-sparing and broad protection against SARS-CoV-2 variants.
Main Methods:
- Production of a recombinant prefusion S-Trimer antigen.
- Vaccination of mice with S-Trimer (0.5, 5, or 20 μg) plus Alum or SWE adjuvant, or no adjuvant.
- Assessment of antibody and T-cell responses, including follicular helper T-cells (Tfh) and germinal center (GC) B cells in mice.
- Evaluation of protective efficacy in a Syrian hamster model against live SARS-CoV-2, including variants.
Main Results:
- SWE adjuvant induced potent humoral and Th1-biased cellular immune responses in mice, outperforming Alum.
- S-Trimer/SWE formulation generated high levels of neutralizing antibodies against original SARS-CoV-2 and variants (Beta, Delta).
- SWE demonstrated a dose-sparing effect, with 0.5 μg S-Trimer inducing protective immunity comparable to higher doses.
Conclusions:
- SWE is an effective adjuvant for enhancing the immunogenicity of the S-Trimer vaccine.
- The S-Trimer/SWE vaccine candidate shows promise for broad protection against SARS-CoV-2 and its variants.
- This vaccine formulation is suitable for further clinical development and global distribution.
