Adjuvanted SARS-CoV-2 spike protein elicits neutralizing antibodies and CD4 T cell responses after a single immunization in mice
| Autor: | Gabriel K. Pedersen, Signe Tandrup Schmidt, Dennis Christensen, Gunilla B. Karlsson Hedestam, Ben Murrel, Julie Zimmermann, Daniel J. Sheward, Leo Hanke, Katharina Wørzner, Gerald M. McInerney |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes medicine.medical_treatment lcsh:Medicine Aluminum Hydroxide Antibodies Viral MF59TM Squalene chemistry.chemical_compound Mice 0302 clinical medicine Cationic liposome 050207 economics Alum media_common lcsh:R5-920 050208 finance biology 05 social sciences Interleukin-17 General Medicine 3. Good health Titer CAF®01 030220 oncology & carcinogenesis Spike Glycoprotein Coronavirus Vaccines Subunit Female Antibody lcsh:Medicine (General) Adjuvant Squalene emulsion Research Paper Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Protein subunit Neutralizing antibodies Subunit vaccine General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Interferon-gamma Adjuvants Immunologic 0502 economics and business medicine media_common.cataloged_instance Animals European union business.industry SARS-CoV-2 lcsh:R COVID-19 Virology Antibodies Neutralizing Mice Inbred C57BL 030104 developmental biology chemistry Immunization Liposomes biology.protein business |
| Zdroj: | EBioMedicine EBioMedicine, Vol 63, Iss, Pp 103197-(2021) |
| ISSN: | 2352-3964 |
| DOI: | 10.1016/j.ebiom.2020.103197 |
| Popis: | Background: SARS-CoV-2 has caused a global pandemic, infecting millions of people. A safe, effective vaccine is urgently needed and remains a global health priority. Subunit vaccines are used successfully against other viruses when administered in the presence of an effective adjuvant. Methods: We evaluated three different clinically tested adjuvant systems in combination with the SARS-CoV-2 pre-fusion stabilized (S-2P) spike protein using a one-dose regimen in mice. Findings: Whilst spike protein alone was only weakly immunogenic, the addition of either Aluminum hydroxide, a squalene based oil-in-water emulsion system (SE) or a cationic liposome-based adjuvant significantly enhanced antibody responses against the spike receptor binding domain (RBD). Kinetics of antibody responses differed, with SE providing the most rapid response. Neutralizing antibodies developed after a single immunization in all adjuvanted groups with ID 50 titers ranging from 86 - 4063. Spike-specific CD4 T helper responses were also elicited, comprising mainly of IFN-g and IL-17 producing cells in the cationic liposome adjuvanted group, and more IL-5- and IL-10-secreting cells in the AH group. Interpretation: These results demonstrate that adjuvanted spike protein subunit vaccine is a viable strategy for rapidly eliciting SARS-CoV-2 neutralizing antibodies and CD4 T cell responses of various qualities depending on the adjuvant used, which can be explored in further vaccine development against COVID-19. Funding: This work was supported by the European Union Horizon 2020 research and innovation program under grant agreement no. 101003653. Declaration of Interests: D.C. is co-inventor on patents on the cationic adjuvant formulations (CAF). All rights have been turned over to Statens Serum Institut, which is a non-profit government research facility. The rest of the authors declare that there are no competing interests. Ethics Approval Statement: Mouse studies were conducted in accordance with the regulations set forth by the National Committee for the Protection of Animals used for Scientific Purposes and in accordance with European Community Directive 86/609. The experiments have been approved by the governmental Animal Experiments Inspectorate under license 2017-15- 0201-01363. |
| Databáze: | OpenAIRE |
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