TY - JOUR
T1 - Immunization of neonatal mice with LAMP/p55 HIV gag DNA elicits robust immune responses that last to adulthood
AU - Rigato, Paula Ordonhez
AU - Maciel, Milton
AU - Goldoni, Adriana Letícia
AU - Piubelli, Orlando
AU - de Brito, Cyro Alves
AU - Fusaro, Ana Elisa
AU - Eurico de Alencar, Liciana Xavier
AU - August, Thomas
AU - Azevedo Marques, Ernesto Torres
AU - da Silva Duarte, Alberto José
AU - Sato, Maria Notomi
N1 - Funding Information:
We thank Vilma dos Anjos Mesquita for the dedicated animal care, and Noemia Orii and Soraya Ogusuko for valuable technical assistance. We thank Luis Carlos Ferreira for providing p24 Gag from HIV-1. This work was supported by CNPq ( 141487/2005 ), FAPESP ( 2004/14443-2 ), Ministério da Saúde do Brasil — Programa Nacional de HIV/AIDS/DST ( 914BRA1101 ) and LIM-56/HCFMUSP .
PY - 2010/10
Y1 - 2010/10
N2 - 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-γ, 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.
AB - 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-γ, 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.
KW - DNA vaccine
KW - HIV-1
KW - Immunological memory
KW - Mice
KW - Neonatal
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U2 - 10.1016/j.virol.2010.06.050
DO - 10.1016/j.virol.2010.06.050
M3 - Article
C2 - 20667577
AN - SCOPUS:77956177205
SN - 0042-6822
VL - 406
SP - 37
EP - 47
JO - Virology
JF - Virology
IS - 1
ER -