دورية أكاديمية
Multiantigen pan-sarbecovirus DNA vaccines generate protective T cell immune responses.
| العنوان: | Multiantigen pan-sarbecovirus DNA vaccines generate protective T cell immune responses. |
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| المؤلفون: | van Bergen J; Immunetune BV, Leiden, Netherlands., Camps MG; Department of Immunology, Leiden University Medical Centre, Leiden, Netherlands., Pardieck IN; Department of Immunology, Leiden University Medical Centre, Leiden, Netherlands., Veerkamp D; Department of Immunology, Leiden University Medical Centre, Leiden, Netherlands., Leung WY; Immunetune BV, Leiden, Netherlands.; Synvolux BV, Leiden, Netherlands., Leijs AA; Department of Medical Microbiology, Leiden University Medical Centre, Leiden, Netherlands., Myeni SK; Department of Medical Microbiology, Leiden University Medical Centre, Leiden, Netherlands., Kikkert M; Department of Medical Microbiology, Leiden University Medical Centre, Leiden, Netherlands., Arens R; Department of Immunology, Leiden University Medical Centre, Leiden, Netherlands., Zondag GC; Immunetune BV, Leiden, Netherlands.; Synvolux BV, Leiden, Netherlands., Ossendorp F; Department of Immunology, Leiden University Medical Centre, Leiden, Netherlands. |
| المصدر: | JCI insight [JCI Insight] 2023 Nov 08; Vol. 8 (21). Date of Electronic Publication: 2023 Nov 08. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]- |
| مواضيع طبية MeSH: | Vaccines, DNA* , Severe acute respiratory syndrome-related coronavirus*, Humans ; Mice ; Animals ; CD8-Positive T-Lymphocytes ; Immunity, Cellular ; SARS-CoV-2/genetics ; Epitopes, T-Lymphocyte/genetics |
| مستخلص: | SARS-CoV-2 is the third zoonotic coronavirus to cause a major outbreak in humans in recent years, and many more SARS-like coronaviruses with pandemic potential are circulating in several animal species. Vaccines inducing T cell immunity against broadly conserved viral antigens may protect against hospitalization and death caused by outbreaks of such viruses. We report the design and preclinical testing of 2 T cell-based pan-sarbecovirus vaccines, based on conserved regions within viral proteins of sarbecovirus isolates of human and other carrier animals, like bats and pangolins. One vaccine (CoVAX_ORF1ab) encoded antigens derived from nonstructural proteins, and the other (CoVAX_MNS) encoded antigens from structural proteins. Both multiantigen DNA vaccines contained a large set of antigens shared across sarbecoviruses and were rich in predicted and experimentally validated human T cell epitopes. In mice, the multiantigen vaccines generated both CD8+ and CD4+ T cell responses to shared epitopes. Upon encounter of full-length spike antigen, CoVAX_MNS-induced CD4+ T cells were responsible for accelerated CD8+ T cell and IgG Ab responses specific to the incoming spike, irrespective of its sarbecovirus origin. Finally, both vaccines elicited partial protection against a lethal SARS-CoV-2 challenge in human angiotensin-converting enzyme 2-transgenic mice. These results support clinical testing of these universal sarbecovirus vaccines for pandemic preparedness. |
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| فهرسة مساهمة: | Keywords: COVID-19; MHC class 1; MHC class 2; T cells; Vaccines |
| المشرفين على المادة: | 0 (Vaccines, DNA) 0 (Epitopes, T-Lymphocyte) |
| تواريخ الأحداث: | Date Created: 20230914 Date Completed: 20231109 Latest Revision: 20231216 |
| رمز التحديث: | 20231216 |
| مُعرف محوري في PubMed: | PMC10721273 |
| DOI: | 10.1172/jci.insight.172488 |
| PMID: | 37707962 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2379-3708 |
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| DOI: | 10.1172/jci.insight.172488 |