title: Mucosal and systemic anti-GAG immunity induced by neonatal immunization with HIV LAMP/gag DNA vaccine in mice.
abstract: Vaccines capable of inducing mucosal immunity in early postnatal life until adulthood, protecting early sexual initiation, should be considered as strategies to vaccination against HIV. The HIV-1 GAG protein as a chimera with the lysosome-associated membrane protein (LAMP/gag), encoded by a DNA vaccine, is targeted to the endosomal/lysosomal compartment that contains class II MHC molecules and has been shown to be immunogenic in adult mice. Assuming that one such strategy could help to overcome the immunological immaturity in the early postnatal period, we have evaluated the systemic and mucosal immunogenicity of LAMP/gag immunization in neonatal mice. Intranasal immunization with LAMP/gag vaccine induced higher levels of sIgA and IgG anti-GAG antibodies in intestinal washes than did the gag vaccine. The combination of ID injections and the IN protocol with the chimeric vaccine promoted the increase of Ab levels in sera. Both vaccines induced splenic IFN-γ- secreting cells against GAG peptide pools, as well as in vivo cytotoxic T lymphocyte (CTL) function, and increased the percentage of CD8+ T cells to the immunodominant class I peptide in gut and spleen. However, only the chimeric vaccine was able to enhance Th1/Th2 cytokine secretion in response to class II GAG peptide and to enhance IL-4-secreting cells against GAG peptides and p24 protein stimuli. Long-lasting humoral and cellular responses were detected until adult age, following neonatal immunization with the chimeric vaccine. The LAMP/gag vaccination was able to induce potent GAG-specific T and B cell immune responses in early life which are essential to elicit sustained and long-lasting mucosal and systemic humoral response.
authors.affiliation: Laboratory of Dermatology and Immunodeficiency - LIM56, School of Medicine, University of São Paulo, Brazil.
authors.forename: Adriana Letícia
authors.initials: AL
authors.lastname: Goldoni
authors.forename: Milton
authors.initials: M
authors.lastname: Maciel
authors.forename: Paula Ordonhez
authors.initials: PO
authors.lastname: Rigato
authors.forename: Orlando
authors.initials: O
authors.lastname: Piubelli
authors.forename: Cyro Alves
authors.initials: CA
authors.lastname: de Brito
authors.forename: Andrea
authors.initials: A
authors.lastname: Melo
authors.forename: Ernesto Torres
authors.initials: ET
authors.lastname: Marques
authors.forename: Joseph Thomas
authors.initials: JT
authors.lastname: August
authors.forename: Alberto José da Silva
authors.initials: AJ
authors.lastname: Duarte
authors.forename: Maria Notomi
authors.initials: MN
authors.lastname: Sato
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics / Q000378:metabolism; D005260:Female; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000276:immunology; D018928:Immunity, Mucosal / Q000276:immunology*; D007114:Immunization; D007071:Immunoglobulin A, Secretory / Q000276:immunology; D051907:Lysosomal Membrane Proteins / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D016207:Cytokines; D015683:Gene Products, gag; D015483:HIV Antibodies; D007071:Immunoglobulin A, Secretory; D051907:Lysosomal Membrane Proteins; D019444:Vaccines, DNA