Combination of a Sindbis-SARS-CoV-2 Spike Vaccine and αOX40 Antibody Elicits Protective Immunity Against SARS-CoV-2 Induced Disease and Potentiates Long-Term SARS-CoV-2-Specific Humoral and T-Cell Immunity
| العنوان: | Combination of a Sindbis-SARS-CoV-2 Spike Vaccine and αOX40 Antibody Elicits Protective Immunity Against SARS-CoV-2 Induced Disease and Potentiates Long-Term SARS-CoV-2-Specific Humoral and T-Cell Immunity |
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| المؤلفون: | Maria G. Noval, Daniel Meruelo, Sara A Thannickal, Silvana Opp, Kenneth A. Stapleford, Alicia Hurtado, Christine Pampeno, Ziyan Lin, Antonella Scaglione |
| المصدر: | bioRxiv Frontiers in Immunology, Vol 12 (2021) Frontiers in Immunology |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, alphavirus vaccine, COVID19, T-Lymphocytes, medicine.disease_cause, Antibodies, Viral, Mice, 0302 clinical medicine, SARS-CoV-2 vaccine, Cricetinae, Immunology and Allergy, Original Research, Coronavirus, education.field_of_study, biology, Sindbis virus vaccine, Effector, Vaccination, 030220 oncology & carcinogenesis, Spike Glycoprotein, Coronavirus, Female, Angiotensin-Converting Enzyme 2, Antibody, Sindbis virus, synergistic combination SARS-CoV-2 vaccine strategy, COVID-19 Vaccines, Immunology, Population, Mice, Transgenic, Alphavirus, Article, 03 medical and health sciences, Immune system, medicine, Animals, Humans, education, SARS-CoV-2, SARS-CoV-2 immunity, COVID-19, RC581-607, biology.organism_classification, Virology, Antibodies, Neutralizing, Antigens, Differentiation, Mice, Inbred C57BL, 030104 developmental biology, HEK293 Cells, Immunization, αOX40, biology.protein, Sindbis Virus, Immunologic diseases. Allergy |
| الوصف: | The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 is a major global public threat. Currently, a worldwide effort has been mounted to generate billions of effective SARS-CoV-2 vaccine doses to immunize the world’s population at record speeds. However, there is still demand for alternative effective vaccines that rapidly confer long-term protection and rely upon cost-effective, easily scaled-up manufacturing. Here, we present a Sindbis alphavirus vector (SV), transiently expressing the SARS-CoV-2 spike protein (SV.Spike), combined with the OX40 immunostimulatory antibody (αOX40) as a novel, highly effective vaccine approach. We show that SV.Spike plus αOX40 elicits long-lasting neutralizing antibodies and a vigorous T-cell response in mice. Protein binding, immunohistochemical and cellular infection assays all show that vaccinated mice sera inhibits spike functions. Immunophenotyping, RNA Seq transcriptome profiles and metabolic analysis indicate a reprogramming of T-cells in vaccinated mice. Activated T-cells were found to mobilize to lung tissue. Most importantly, SV.Spike plus αOX40 provided robust immune protection against infection with authentic coronavirus in transgenic mice expressing the human ACE2 receptor (hACE2-Tg). Finally, our immunization strategy induced strong effector memory response, potentiating protective immunity against re-exposure to SARS-CoV-2 spike protein. Our results show the potential of a new Sindbis virus-based vaccine platform to counteract waning immune response that can be used as a new candidate to combat SARS-CoV-2. Given the strong T-cell responses elicited, our vaccine is likely to be effective against variants that are proving challenging, as well as, serve as a platform to develop a broader spectrum pancoronavirus vaccine. Similarly, the vaccine approach is likely to be applicable to other pathogens. |
| تدمد: | 1664-3224 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4dab2762d1344c8ac86bb9b5246cb0feTest https://pubmed.ncbi.nlm.nih.gov/34075383Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4dab2762d1344c8ac86bb9b5246cb0fe |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16643224 |
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