title: Immunization of neonatal mice with LAMP/p55 HIV gag DNA elicits robust immune responses that last to adulthood.
abstract: Successful T cell priming in early postnatal life that can generate effective long-lasting responses until adulthood is critical in HIV vaccination strategies because it prevents early sexual initiation and breastfeeding transmission of HIV. A chimeric DNA vaccine encoding p55 HIV gag associated with lysosome-associated membrane protein 1 (LAMP-1; which drives the antigen to the MIIC compartment), has been used to enhance cellular and humoral antigen-specific responses in adult mice and macaques. Herein, we investigated LAMP-1/gag vaccine immunogenicity in the neonatal period in mice and its ability to generate long-lasting effects. Neonatal vaccination with chimeric LAMP/gag generated stronger Gag-specific immune responses, as measured by the breadth of the Gag peptide-specific IFN-gamma, proliferative responsiveness, cytokine production and antibody production, all of which revealed activation of CD4+ T cells as well as the generation of a more robust CTL response compared to gag vaccine alone. To induce long-lived T and B cell memory responses, it was necessary to immunize neonates with the chimeric LAMP/gag DNA vaccine. The LAMP/gag DNA vaccine strategy could be particularly useful for generating an anti-HIV immune response in the early postnatal period capable of inducing long-term immunological memory.
authors.affiliation: Laboratory of Dermatology and Immunodeficiency, LIM-56, School of Medicine, University of São Paulo, Brazil.
authors.forename: Paula Ordonhez
authors.initials: PO
authors.lastname: Rigato
authors.forename: Milton
authors.initials: M
authors.lastname: Maciel
authors.forename: Adriana Letícia
authors.initials: AL
authors.lastname: Goldoni
authors.forename: Orlando
authors.initials: O
authors.lastname: Piubelli
authors.forename: Cyro Alves
authors.initials: CA
authors.lastname: de Brito
authors.forename: Ana Elisa
authors.initials: AE
authors.lastname: Fusaro
authors.forename: Liciana Xavier
authors.initials: LX
authors.lastname: Eurico de Alencar
authors.forename: Thomas
authors.initials: T
authors.lastname: August
authors.forename: Ernesto Torres
authors.initials: ET
authors.lastname: Azevedo Marques
authors.forename: Alberto José
authors.initials: AJ
authors.lastname: da Silva 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; D000831:Animals, Newborn; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D007114:Immunization; D007117:Immunization, Secondary; D007156:Immunologic Memory; D052118:Lysosomal-Associated Membrane Protein 1 / Q000235:genetics* / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011498:Protein Precursors / Q000235:genetics* / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D052118:Lysosomal-Associated Membrane Protein 1; D011498:Protein Precursors; D019444:Vaccines, DNA; C059767:p55 gag precursor protein, Human immunodeficiency virus 1