Immunization of neonatal mice with LAMP/p55 HIV gag DNA elicits robust immune responses that last to adulthood.
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.
Rigato
Paula Ordonhez
PO
Laboratory of Dermatology and Immunodeficiency, LIM-56, School of Medicine, University of São Paulo, Brazil.
Maciel
Milton
M
Goldoni
Adriana Letícia
AL
Piubelli
Orlando
O
de Brito
Cyro Alves
CA
Fusaro
Ana Elisa
AE
Eurico de Alencar
Liciana Xavier
LX
August
Thomas
T
Azevedo Marques
Ernesto Torres
ET
da Silva Duarte
Alberto José
AJ
Sato
Maria Notomi
MN
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
D016915:AIDS Vaccines; D052118:Lysosomal-Associated Membrane Protein 1; D011498:Protein Precursors; D019444:Vaccines, DNA; C059767:p55 gag precursor protein, Human immunodeficiency virus 1