Durable immunity to SARS-CoV-2 in both lower and upper airways achieved with a gorilla adenovirus (GRAd) S-2P vaccine in non-human primates.

Autor:	Moliva JI; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America.; National Emerging Infectious Diseases Laboratories, Boston University, Boston, Massachusetts, United States of America., Andrew SF; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America., Flynn BJ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America., Wagner DA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America., Foulds KE; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America., Gagne M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America., Flebbe DR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America., Lamb E; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America., Provost S; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America., Marquez J; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America., Mychalowych A; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America., Lorag CG; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America., Honeycutt CC; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America., Burnett MR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America., McCormick L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America., Henry AR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America., Godbole S; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America., Davis-Gardner ME; Department of Pediatrics, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, Georgia, 30322, United States of America., Minai M; Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, 20892, United States of America., Bock KW; Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, 20892, United States of America., Nagata BM; Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, 20892, United States of America., Todd JM; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America., McCarthy E; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America., Dodson A; Bioqual, Inc., Rockville, Maryland, 20850, United States of America., Kouneski K; Bioqual, Inc., Rockville, Maryland, 20850, United States of America., Cook A; Bioqual, Inc., Rockville, Maryland, 20850, United States of America., Pessaint L; Bioqual, Inc., Rockville, Maryland, 20850, United States of America., Ry AV; Bioqual, Inc., Rockville, Maryland, 20850, United States of America., Valentin D; Bioqual, Inc., Rockville, Maryland, 20850, United States of America., Young S; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America., Littman Y; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America., Boon ACM; Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, 63110, United States of America., Suthar MS; Department of Pediatrics, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, Georgia, 30322, United States of America., Lewis MG; Bioqual, Inc., Rockville, Maryland, 20850, United States of America., Andersen H; Bioqual, Inc., Rockville, Maryland, 20850, United States of America., Alves DA; Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, 20892, United States of America., Woodward R; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America., Leuzzi A; ReiThera Srl, 00128 Rome, Republic of Italy., Vitelli A; ReiThera Srl, 00128 Rome, Republic of Italy., Colloca S; ReiThera Srl, 00128 Rome, Republic of Italy., Folgori A; ReiThera Srl, 00128 Rome, Republic of Italy., Raggiolli A; ReiThera Srl, 00128 Rome, Republic of Italy., Capone S; ReiThera Srl, 00128 Rome, Republic of Italy., Nason MC; Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America., Douek DC; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America., Roederer M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America., Seder RA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America.; Correspondence: rseder@mail.nih.gov and njsull@bu.edu., Sullivan NJ; National Emerging Infectious Diseases Laboratories, Boston University, Boston, Massachusetts, United States of America.; Correspondence: rseder@mail.nih.gov and njsull@bu.edu.; Lead contact.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Nov 22. Date of Electronic Publication: 2023 Nov 22.
DOI:	10.1101/2023.11.22.567930
Abstrakt:	SARS-CoV-2 continues to pose a global threat, and current vaccines, while effective against severe illness, fall short in preventing transmission. To address this challenge, there's a need for vaccines that induce mucosal immunity and can rapidly control the virus. In this study, we demonstrate that a single immunization with a novel gorilla adenovirus-based vaccine (GRAd) carrying the pre-fusion stabilized Spike protein (S-2P) in non-human primates provided protective immunity for over one year against the BA.5 variant of SARS-CoV-2. A prime-boost regimen using GRAd followed by adjuvanted S-2P (GRAd+S-2P) accelerated viral clearance in both the lower and upper airways. GRAd delivered via aerosol (GRAd(AE)+S-2P) modestly improved protection compared to its matched intramuscular regimen, but showed dramatically superior boosting by mRNA and, importantly, total virus clearance in the upper airway by day 4 post infection. GrAd vaccination regimens elicited robust and durable systemic and mucosal antibody responses to multiple SARS-CoV-2 variants, but only GRAd(AE)+S-2P generated long-lasting T cell responses in the lung. This research underscores the flexibility of the GRAd vaccine platform to provide durable immunity against SARS-CoV-2 in both the lower and upper airways. Competing Interests: Declaration of interests M.R., N.J.S., and D.C.D. are inventors on U.S. Patent Application No. 63/147,419 entitled “Antibodies Targeting the Spike Protein of Coronaviruses”. L.P., A.V.R., D.V., A.C., A.D., M.G.L., and H.A. are employees of Bioqual, Inc. A.L., A.V., S.Co., A.F., A.R., and S.Ca. are employees of ReiThera Srl. S.Co. and A.F. are shareholders of Keires AG. A.V., S.Co. and A.R. are named inventors of the Patent Application No. 20183515.4 entitled “Gorilla Adenovirus Nucleic Acid- and Amino Acid-Sequences, Vectors Containing Same, and Uses Thereof”. The other authors declare no competing interests.
Databáze:	MEDLINE
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