title: Different HIV pox viral vector-based vaccines and adjuvants can induce unique antigen presenting cells that modulate CD8 T cell avidity.
abstract: The lung-derived dendritic cell (LDC) recruitment following intranasal (i.n.) vaccination of different poxviral vector-based vaccines/adjuvants were evaluated to decipher how these factors influenced CD8(+) T cell avidity. Compared to the standard i.n. recombinant fowlpox virus (FPV)-HIV vaccination, the FPV-HIV IL-13Rα2 or IL-4Rα antagonist adjuvanted vaccines that induced higher avidity CD8(+) T cells, also recruited significantly elevated MHCII(+) CD11c(+) CD11b(+) CD103(-) CD64(-) MAR-1(-) conventional DC (cDCs) to the lung mucosae (hierarchy: IL-4R antagonist>IL-13Rα2>unadjuvanted). In contrast, elevated CD11b(-) CD103(+) LDCs were detected in animals that received recombinant HIV vaccinia virus (rVV) or Modified Vaccinia Ankara virus (MVA) vector-based vaccines. Adoptive transfer studies indicated that CD11b(-) CD103(+) LDCs significantly dampened HIV-specific CD8(+) T cell avidity compared to CD11b(+) CD103(-) LDCs. Collectively; our observations revealed that rFPV vector prime and transient inhibition of IL-4/IL-13 at the vaccination site favoured the recruitment of unique LDCs, associated with the induction of high quality immunity.
authors.affiliation: Molecular Mucosal Vaccine Immunology Group, Department of Immunology, The John Curtin School of Medical Research, The Australian National University, Canberra ACT 0200, Australia. Electronic address: shubhanshi.trivedi@anu.edu.au.
authors.forename: Shubhanshi
authors.initials: S
authors.lastname: Trivedi
authors.affiliation: Molecular Mucosal Vaccine Immunology Group, Department of Immunology, The John Curtin School of Medical Research, The Australian National University, Canberra ACT 0200, Australia.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Jackson
authors.affiliation: Molecular Mucosal Vaccine Immunology Group, Department of Immunology, The John Curtin School of Medical Research, The Australian National University, Canberra ACT 0200, Australia.
authors.forename: Charani
authors.initials: C
authors.lastname: Ranasinghe
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology*; D015703:Antigens, CD; D039481:CD11b Antigen; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D005260:Female; D039001:Integrin alpha Chains; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D053659:Receptors, Interleukin-4, Type II / Q000276:immunology; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D039481:CD11b Antigen; D039001:Integrin alpha Chains; D018793:Interleukin-13; D053659:Receptors, Interleukin-4, Type II; C091367:alpha E integrins
keywords: CD8(+) T cell avidity; HIV vaccines; IL-13Rα2/IL-4R antagonist; Lung dendritic cells; Poxvirus vectors