title: Prime-boost immunization schedules based on influenza virus and vaccinia virus vectors potentiate cellular immune responses against human immunodeficiency virus Env protein systemically and in the genitorectal draining lymph nodes.
abstract: Vaccines that elicit systemic and mucosal immune responses should be the choice to control human immunodeficiency virus (HIV) infections. We have previously shown that prime-boost immunizations with influenza virus Env and vaccinia virus (VV) WR Env recombinants induced an enhanced systemic CD8(+) T-cell response against HIV-1 Env antigen. In this report, we analyzed in BALB/c mice after priming with influenza virus Env the ability of two VV recombinants expressing HIV-1 Env B (VV WR Env and the highly attenuated modified VV Ankara [MVA] Env) to boost cellular immune responses in the spleen and in the lymph nodes draining the genital and rectal tracts. Groups of mice were primed by the intranasal route with 10(4) PFU of influenza virus Env and boosted 14 days later by the intraperitoneal or intranasal route with 10(7) PFU of MVA Env or VV WR Env, while the control group received two immunizations with influenza virus Env. We found that the combined immunization (Flu/VV) increased more than 60 times the number of gamma interferon-specific CD8(+) T cells compared to the Flu/Flu scheme. Significantly, boosting with MVA Env by the intraperitoneal route induced a response 1.25 or 2.5 times (spleen or genital lymph nodes) higher with respect to that found after the boost with VV WR Env. Mice with an enhanced CD8(+) T-cell response also had an increased Th1/Th2 ratio, evaluated by the cytokine pattern secreted following in vitro restimulation with gp160 protein and by the specific immunoglobulin G2a (IgG2a)/IgG1 ratio in serum. By the intranasal route recombinant WR Env booster gave a more efficient immune response (10 and 1.3 times in spleen and genital lymph nodes, respectively) than recombinant MVA Env. However, the scheme influenza virus Env/MVA Env increased four times the response in the spleen, giving a low but significant response in the genital lymph nodes compared with a single intranasal immunization with MVA Env. These results demonstrate that the combination Flu/MVA in prime-booster immunization regimens is an effective vaccination approach to generate cellular immune responses to HIV antigens at sites critical for protective responses.
authors.affiliation: Department of Molecular and Cellular Biology, Centro Nacional de Biotecnologia, CSIC, Campus Universidad Autónoma, 28049 Madrid, Spain.
authors.forename: M Magdalena
authors.initials: MM
authors.lastname: Gherardi
authors.forename: José Luis
authors.initials: JL
authors.lastname: Nájera
authors.forename: Eva
authors.initials: E
authors.lastname: Pérez-Jiménez
authors.forename: Susana
authors.initials: S
authors.lastname: Guerra
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.forename: Mariano
authors.initials: M
authors.lastname: Esteban
mesh_terms: D016475:3T3 Cells; D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000276:immunology; D005835:Genitalia / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000517:prevention & control; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009975:Orthomyxoviridae / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D011995:Recombination, Genetic; D012007:Rectum / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D015686:Gene Products, env; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments