title: Unique cellular and humoral immunogenicity profiles generated by aerosol, intranasal, or parenteral vaccination in rhesus macaques.
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 10μm 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 4μm 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.
authors.affiliation: ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, United States.
authors.forename: Diane L
authors.initials: DL
authors.lastname: Bolton
authors.affiliation: ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, United States.
authors.forename: Kaimei
authors.initials: K
authors.lastname: Song
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, United States.
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.affiliation: ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, United States.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Rao
authors.affiliation: ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, United States. Electronic address: roederer@nih.gov.
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
mesh_terms: D000280:Administration, Inhalation; D000281:Administration, Intranasal; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007267:Injections; D008253:Macaca mulatta; D014612:Vaccines / Q000008:administration & dosage* / Q000276:immunology*
chemical_list: D014612:Vaccines
keywords: Aerosol; Immunogenicity; Nasal; Rhesus macaque; Vaccine delivery route