Thermophilic Filamentous Fungus C1-Cell-Cloned SARS-CoV-2-Spike-RBD-Subunit-Vaccine Adjuvanted with Aldydrogel®85 Protects K18-hACE2 Mice against Lethal Virus Challenge
| Autor: | Ram Nechooshtan, Sharon Ehrlich, Marika Vitikainen, Arik Makovitzki, Eyal Dor, Hadar Marcus, Idan Hefetz, Shani Pitel, Marilyn Wiebe, Anne Huuskonen, Lilach Cherry, Edith Lupu, Yehuda Sapir, Tzvi Holtzman, Moshe Aftalion, David Gur, Hadas Tamir, Yfat Yahalom-Ronen, Yuval Ramot, Noam Kronfeld, David Zarling, Anne Vallerga, Ronen Tchelet, Abraham Nyska, Markku Saloheimo, Mark Emalfarb, Yakir Ophir |
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| Rok vydání: | 2022 |
| Předmět: |
glycoprotein
intranasal challenge K18-hACE-2 mice recombinant protein subunit vaccine biomanufacturing glycosylation aluminum-based vaccine adjuvants IgG efficacy Immunology dyadic virus variants of concern IgG1 and IgG2b RBD Thermothelomyces heterothallica antigen baculovirus adjuvant C-tag SDG 3 - Good Health and Well-being vaccine CHO-cell Drug Discovery BALB/c mice neutralizing antibodies Pharmacology (medical) zoonotic Pharmacology receptor binding domain SARS-CoV-2 pandemic COVID-19 stability Myceliophthora thermophila insect cells toxicology glycans alum Infectious Diseases |
| Zdroj: | Nechooshtan, R, Ehrlich, S, Vitikainen, M, Makovitzki, A, Dor, E, Marcus, H, Hefetz, I, Pitel, S, Wiebe, M, Huuskonen, A, Cherry, L, Lupu, E, Sapir, Y, Holtzman, T, Aftalion, M, Gur, D, Tamir, H, Yahalom-Ronen, Y, Ramot, Y, Kronfeld, N, Zarling, D, Vallerga, A, Tchelet, R, Nyska, A, Saloheimo, M, Emalfarb, M & Ophir, Y 2022, ' Thermophilic Filamentous Fungus C1-Cell-Cloned SARS-CoV-2-Spike-RBD-Subunit-Vaccine Adjuvanted with Aldydrogel ® 85 Protects K18-hACE2 Mice against Lethal Virus Challenge ', Vaccines, vol. 10, no. 12, 2119 . https://doi.org/10.3390/vaccines10122119 Vaccines; Volume 10; Issue 12; Pages: 2119 |
| ISSN: | 2076-393X |
| DOI: | 10.3390/vaccines10122119 |
| Popis: | SARS-CoV-2 is evolving with increased transmission, host range, pathogenicity, and virulence. The original and mutant viruses escape host innate (Interferon) immunity and adaptive (Antibody) immunity, emphasizing unmet needs for high-yield, commercial-scale manufacturing to produce inexpensive vaccines/boosters for global/equitable distribution. We developed DYAI-100A85, a SARS-CoV-2 spike receptor binding domain (RBD) subunit antigen vaccine expressed in genetically modified thermophilic filamentous fungus, Thermothelomyces heterothallica C1, and secreted at high levels into fermentation medium. The RBD-C-tag antigen strongly binds ACE2 receptors in vitro. Alhydrogel®‘85’-adjuvanted RDB-C-tag-based vaccine candidate (DYAI-100A85) demonstrates strong immunogenicity, and antiviral efficacy, including in vivo protection against lethal intranasal SARS-CoV-2 (D614G) challenge in human ACE2-transgenic mice. No loss of body weight or adverse events occurred. DYAI-100A85 also demonstrates excellent safety profile in repeat-dose GLP toxicity study. In summary, subcutaneous prime/boost DYAI-100A85 inoculation induces high titers of RBD-specific neutralizing antibodies and protection of hACE2-transgenic mice against lethal challenge with SARS-CoV-2. Given its demonstrated safety, efficacy, and low production cost, vaccine candidate DYAI-100 received regulatory approval to initiate a Phase 1 clinical trial to demonstrate its safety and efficacy in humans. |
| Databáze: | OpenAIRE |
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