Unique cellular and humoral immunogenicity profiles generated by aerosol,intranasal, or parenteral vaccination in rhesus macaques |
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| Affiliation: | 1. ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, United States;2. Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, United States;1. Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA;2. Dept. of Veterinary Diagnostic and Production Animal Medicine, Iowa State University, Ames, IA, USA;3. Codagenix Inc., Farmingdale, NY, USA;4. Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS, 1920 Dayton Ave, Ames, IA 50010, USA;1. Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan;2. Department of Life Science and Medical Bioscience, Waseda University, Shinjuku-ku, Tokyo 162-8480, Japan;3. Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan;1. College of Life Sciences & Bioengineering, Beijing Jiaotong University, Beijing, 100044, China;2. Institute of Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 100052, China;1. BlueWillow Biologics, Ann Arbor, MI, United States;2. Fraunhofer USA Center for Molecular Biotechnology (FhCMB), Newark, DE, United States;1. McMaster Immunology Research Centre and Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada;2. Department of Chemical Engineering, McMaster University, Hamilton, Ontario, Canada;3. Department of Immunology, The Wistar Institute, Philadelphia, PA, USA |
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| Abstract: | Respiratory mucosa immunization is capable of eliciting both local and distal mucosal immune responses; it is a potentially powerful yet largely unused modality for vaccination against respiratory diseases. Targeting the lower versus upper airways by aerosol delivery alters the immunogenicity profile of a vaccine, although the full extent of this impact is not well characterized. We set out to define the cellular and humoral response profiles elicited by immunization via intranasal, small aerosol droplets, and large aerosol droplets. We compared responses following adenovirus-vectored vaccination by these routes in macaques, either for the generation of primary immune responses or for the boosting of previously primed systemic responses. Aerosol delivery (4 or 10 μm diameter droplets, addressing lower or upper airways, respectively) generated the highest magnitude lung CD4 and CD8 T-cell responses, reaching 10–30% vaccine-specific levels in bronchoalveolar lavage cells. In contrast, intranasal delivery was less immunogenic with >10-fold lower peak lung T-cell responses. Systemic (blood) T-cell responses were only observed following 4 μm aerosol (and parenteral) immunization, while all delivery routes elicited similar humoral responses. These data demonstrate distinct immune response profiles with each respiratory tract vaccination modality and suggest that small droplet aerosol offers several immunological advantages over other respiratory routes. |
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| Keywords: | Aerosol Nasal Vaccine delivery route Immunogenicity Rhesus macaque |
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