title: A comparative analysis of HIV-specific mucosal/systemic T cell immunity and avidity following rDNA/rFPV and poxvirus-poxvirus prime boost immunisations.
abstract: In this study we have firstly compared a range of recombinant DNA poxvirus prime-boost immunisation strategies and shown that combined intramuscular (i.m.) 2× DNA-HIV/intranasal (i.n.) 2× FPV-HIV prime-boost immunisation can generate high-level of HIV-specific systemic (spleen) and mucosal (genito-rectal nodes, vaginal tissues and lung tissues) T cell responses and HIV-1 p24 Gag-specific serum IgG1, IgG2a and mucosal IgG, SIgA responses in vaginal secretions in BALB/c mice. Data indicate that following rDNA priming, two rFPV booster immunisations were necessary to generate good antibody and mucosal T cell immunity. This data also revealed that mucosal uptake of recombinant fowl pox (rFPV) was far superior to plasmid DNA. To further evaluate CD8+ T cell immunity, i.m. 2× DNA-HIV/i.n. 1× FPV-HIV immunisation strategy was directly compared with single shot poxvirus/poxvirus, i.n. FPV-HIV/i.m. VV-HIV immunisation. Results indicate that the latter strategy was able to generate strong sustained HIV-specific CD8+ T cells with higher avidity, broader cytokine/chemokine profiles and better protection following influenza-K(d)Gag(197-205) challenge compared to rDNA poxvirus prime-boost strategy. Our findings further substantiate the importance of vector selection/combination, order and route of delivery when designing effective vaccines for HIV-1.
authors.affiliation: The John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia. Charani.Ranasinghe@anu.edu.au
authors.forename: Charani
authors.initials: C
authors.lastname: Ranasinghe
authors.forename: Fiona
authors.initials: F
authors.lastname: Eyers
authors.forename: John
authors.initials: J
authors.lastname: Stambas
authors.forename: David B
authors.initials: DB
authors.lastname: Boyle
authors.forename: Ian A
authors.initials: IA
authors.lastname: Ramshaw
authors.forename: Alistair J
authors.initials: AJ
authors.lastname: Ramsay
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000281:Administration, Intranasal; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005587:Fowlpox virus / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood; D016655:HIV Core Protein p24 / Q000276:immunology; D015658:HIV Infections / Q000517:prevention & control*; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D018928:Immunity, Mucosal; D007117:Immunization, Secondary; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D016655:HIV Core Protein p24; D007376:Interleukin-2; D019444:Vaccines, DNA; C514799:p24 protein, Human Immunodeficiency Virus Type 1; D007371:Interferon-gamma