Mucosal SARS-CoV-2 S1 adenovirus-based vaccine elicits robust systemic and mucosal immunity and protects against disease in animals.

Autor:	Aljehani ND; Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia., Tamming L; Centre for Oncology, Radiopharmaceuticals and Research Biologics and Radiopharmaceutical Drug Directorate, Health Products and Food Branch (HPFB), Health Canada and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Ottawa, Ontario, Canada.; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada., Khan MY; Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia., Abdulal RH; Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia., Alfaleh MA; Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.; Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia., Ghazwani A; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia., Helal A; Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.; Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia., Alsulaiman RM; Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia., Sanki MA; Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia., Alluhaybi K; Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.; Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia., Sukareh FA; Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia., Alharbi RH; Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia., Alyami FH; Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia., ElAssouli M-Z; Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia., Shebbo S; Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.; College of Dental Medicine, QU Health, Qatar University, Doha, Qatar., Abdulaal WH; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia., Algaissi A; Department of Medical Laboratories Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia., Mahmoud AB; College of Applied Medical Sciences, Taibah University, Almadinah Almunwarah, Saudi Arabia., Basabrain M; Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia., Duque D; Human Health Therapeutics Research Center, National Research Council Canada, Ottawa, Ontario, Canada., Bavananthasivam J; Human Health Therapeutics Research Center, National Research Council Canada, Ottawa, Ontario, Canada., Chen W; Human Health Therapeutics Research Center, National Research Council Canada, Ottawa, Ontario, Canada., Wang L; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada., Sauve S; Centre for Oncology, Radiopharmaceuticals and Research Biologics and Radiopharmaceutical Drug Directorate, Health Products and Food Branch (HPFB), Health Canada and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Ottawa, Ontario, Canada., Abujamel TS; Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia., Altorki T; Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia., Alhabbab R; Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia., Tran A; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.; Human Health Therapeutics Research Center, National Research Council Canada, Ottawa, Ontario, Canada., Li X; Centre for Oncology, Radiopharmaceuticals and Research Biologics and Radiopharmaceutical Drug Directorate, Health Products and Food Branch (HPFB), Health Canada and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Ottawa, Ontario, Canada.; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada., Hashem AM; Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.; Department of Clinical Microbiology and Immunology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Jazyk:	angličtina
Zdroj:	MBio [mBio] 2024 Dec 04, pp. e0217024. Date of Electronic Publication: 2024 Dec 04.
DOI:	10.1128/mbio.02170-24
Abstrakt:	The COVID-19 pandemic has emphasized the importance and need for accessible safe, effective, and versatile vaccine platforms. While approved SARS-CoV-2 vaccines have been instrumental in saving lives and reducing healthcare and economic burdens, the induction of mucosal immunity remains an unmet need. Here, we engineered and evaluated a non-replicating adenovirus 5 (rAd5)-based vaccine expressing the SARS-CoV-2 S1 subunit (rAd5-SARS2-S1). We assessed the immunogenicity, durability, and protective efficacy of intramuscular (IM) and intranasal (IN) administration of rAd5-SARS2-S1 in mice and Syrian hamsters. Two IM or IN doses of rAd5-SARS2-S1 elicited robust and sustained Th1-skewed S1-specific serum IgG, neutralizing antibodies (nAbs) against several SARS-CoV-2 variants and systemic antigen-specific memory T cell responses in mice. Additionally, IN vaccination induced potent and long-lasting mucosal S1-specific IgG, IgA, and nAbs and pulmonary memory T cells. Importantly, while IM vaccine significantly ameliorated disease severity in hamsters by reducing viral burden, lung pathology, and, to some extent, weight loss, IN immunization significantly reduced viral replication and provided superior protection against disease and weight loss. Together, our study demonstrates that the rAd5-SARS2-S1 vaccine is immunogenic in both mice and hamsters when administered intramuscularly or intranasally, with IN administration providing better protection. These findings suggest that IN delivery of rAd5-SARS2-S1 could be a promising approach for inducing mucosal and systemic immunity, offering enhanced protection against SARS-CoV-2 and emerging variants. Importance: This publication presents an assessment of the immune response and effectiveness of a vaccine containing genetically modified non-replicating recombinant that expresses the S1 subunit protein of SARS-CoV-2. We conducted a comparative analysis of the immune response potency, durability, and protective effectiveness of this vaccine using intramuscular (IM) and intranasal (IN) inoculation in mice and Syrian hamsters. Our findings indicate that both vaccinations were effective in stimulating strong and long-lasting immune responses, both locally and across the body, when administered through either IM or IN methods. Crucially, our study demonstrated that the IN vaccination outperformed the IM vaccine by effectively and significantly suppressing the multiplication of the virus in the lungs and nasal turbinates. Additionally, the IN vaccine provided protection against disease-related weight loss and lung damage in the animals. This work showcases the potential of intranasal administration as a viable method to stimulate both mucosal and systemic immunity. This technique provides improved defense against SARS-CoV-2 and maybe additional variations.
Databáze:	MEDLINE
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