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Low-Dose SARS-CoV-2 S-Trimer with an Emulsion Adjuvant Induced Th1-Biased Protective Immunity.
Liao, Hung-Chun; Wu, Wan-Ling; Chiang, Chen-Yi; Huang, Min-Syuan; Shen, Kuan-Yin; Huang, Yu-Ling; Wu, Suh-Chin; Liao, Ching-Len; Chen, Hsin-Wei; Liu, Shih-Jen.
  • Liao HC; National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, Taiwan.
  • Wu WL; Institute of Biotechnology, National Tsing Hua University, Hsinchu 300044, Taiwan.
  • Chiang CY; National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, Taiwan.
  • Huang MS; National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, Taiwan.
  • Shen KY; National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, Taiwan.
  • Huang YL; Institute of Biotechnology, National Tsing Hua University, Hsinchu 300044, Taiwan.
  • Wu SC; National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, Taiwan.
  • Liao CL; School of Dentistry, Tri-Service General Hospital and National Defense Medical Center, Taipei 11490, Taiwan.
  • Chen HW; National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, Taiwan.
  • Liu SJ; Institute of Biotechnology, National Tsing Hua University, Hsinchu 300044, Taiwan.
Int J Mol Sci ; 23(9)2022 Apr 28.
Article in English | MEDLINE | ID: covidwho-1820291
ABSTRACT
During the sustained COVID-19 pandemic, global mass vaccination to achieve herd immunity can prevent further viral spread and mutation. A protein subunit vaccine that is safe, effective, stable, has few storage restrictions, and involves a liable manufacturing process would be advantageous to distribute around the world. Here, we designed and produced a recombinant spike (S)-Trimer that is maintained in a prefusion state and exhibits a high ACE2 binding affinity. Rodents received different doses of S-Trimer (0.5, 5, or 20 µg) antigen formulated with aluminum hydroxide (Alum) or an emulsion-type adjuvant (SWE), or no adjuvant. After two vaccinations, the antibody response, T-cell responses, and number of follicular helper T-cells (Tfh) or germinal center (GC) B cells were assessed in mice; the protective efficacy was evaluated on a Syrian hamster infection model. The mouse studies demonstrated that adjuvating the S-Trimer with SWE induced a potent humoral immune response and Th1-biased cellular immune responses (in low dose) that were superior to those induced by Alum. In the Syrian hamster studies, when S-Trimer was adjuvanted with SWE, higher levels of neutralizing antibodies were induced against live SARS-CoV-2 from the original lineage and against the emergence of variants (Beta or Delta) with a slightly decreased potency. In addition, the SWE adjuvant demonstrated a dose-sparing effect; thus, a lower dose of S-Trimer as an antigen (0.5 µg) can induce comparable antisera and provide complete protection from viral infection. These data support the utility of SWE as an adjuvant to enhance the immunogenicity of the S-Trimer vaccine, which is feasible for further clinical testing.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Th1 Cells / Spike Glycoprotein, Coronavirus / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Prognostic study Topics: Vaccines / Variants Limits: Animals / Humans Language: English Year: 2022 Document Type: Article Affiliation country: Ijms23094902

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Th1 Cells / Spike Glycoprotein, Coronavirus / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Prognostic study Topics: Vaccines / Variants Limits: Animals / Humans Language: English Year: 2022 Document Type: Article Affiliation country: Ijms23094902