Maternal LAMP/p55gagHIV-1 DNA immunization induces in Utero priming and a long-lasting immune response in vaccinated neonates

Paula Ordonhez Rigato, Milton Maciel, Adriana Letícia Goldoni, Orlando Guerra Piubelli, Noemia Mie Orii, Ernesto Torres Marques, Thomas August, Alberto José da Silva Duarte, Maria Notomi Sato

Research output: Contribution to journalArticle

Abstract

Infants born to HIV-infected mothers are at high risk of becoming infected during gestation or the breastfeeding period. A search is thus warranted for vaccine formulations that will prevent mother-to-child HIV transmission. The LAMP/gag DNA chimeric vaccine encodes the HIV-1 p55gag fused to the lysosome-associated membrane protein-1 (LAMP-1) and has been shown to enhance anti-Gag antibody (Ab) and cellular immune responses in adult and neonatal mice; such a vaccine represents a new concept in antigen presentation. In this study, we evaluated the effect of LAMP/gag DNA immunization on neonates either before conception or during pregnancy. LAMP/gag immunization of BALB/c mice before conception by the intradermal route led to the transfer of anti-Gag IgG1 Ab through the placenta and via breastfeeding. Furthermore, there were an increased percentage of CD4+CD25+Foxp3+T cells in the spleens of neonates. When offspring were immunized with LAMP/gag DNA, the anti-Gag Ab response and the Gag-specific IFN-γ-secreting cells were decreased. Inhibition of anti-Gag Ab production and cellular responses were not observed six months after immunization, indicating that maternal immunization did not interfere with the long-lasting memory response in offspring. Injection of purified IgG in conjunction with LAMP/gag DNA immunization decreased humoral and cytotoxic T-cell responses. LAMP/gag DNA immunization by intradermal injection prior to conception promoted the transfer of Ab, leading to a diminished response to Gag without interfering with the development of anti-Gag T- and B-cell memory. Finally, we assessed responses after one intravenous injection of LAMP/gag DNA during the last five days of pregnancy. The intravenous injection led to in utero immunization. In conclusion, DNA vaccine enconding LAMP-1 with Gag and other HIV-1 antigens should be considered in the development of a protective vaccine for the maternal/fetal and newborn periods.

Original languageEnglish (US)
Article numbere31608
JournalPLoS One
Volume7
Issue number2
DOIs
StatePublished - Feb 15 2012

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Immunization
immunization
neonates
Mothers
immune response
Newborn Infant
DNA
Lysosome-Associated Membrane Glycoproteins
Antibodies
vaccines
DNA Vaccines
antibodies
Vaccines
T-cells
T-lymphocytes
breast feeding
lysosomes
pregnancy
Human immunodeficiency virus 1
Breast Feeding

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Rigato, P. O., Maciel, M., Goldoni, A. L., Piubelli, O. G., Orii, N. M., Marques, E. T., ... Sato, M. N. (2012). Maternal LAMP/p55gagHIV-1 DNA immunization induces in Utero priming and a long-lasting immune response in vaccinated neonates. PLoS One, 7(2), [e31608]. https://doi.org/10.1371/journal.pone.0031608

Maternal LAMP/p55gagHIV-1 DNA immunization induces in Utero priming and a long-lasting immune response in vaccinated neonates. / Rigato, Paula Ordonhez; Maciel, Milton; Goldoni, Adriana Letícia; Piubelli, Orlando Guerra; Orii, Noemia Mie; Marques, Ernesto Torres; August, Thomas; da Silva Duarte, Alberto José; Sato, Maria Notomi.

In: PLoS One, Vol. 7, No. 2, e31608, 15.02.2012.

Research output: Contribution to journalArticle

Rigato, PO, Maciel, M, Goldoni, AL, Piubelli, OG, Orii, NM, Marques, ET, August, T, da Silva Duarte, AJ & Sato, MN 2012, 'Maternal LAMP/p55gagHIV-1 DNA immunization induces in Utero priming and a long-lasting immune response in vaccinated neonates', PLoS One, vol. 7, no. 2, e31608. https://doi.org/10.1371/journal.pone.0031608
Rigato, Paula Ordonhez ; Maciel, Milton ; Goldoni, Adriana Letícia ; Piubelli, Orlando Guerra ; Orii, Noemia Mie ; Marques, Ernesto Torres ; August, Thomas ; da Silva Duarte, Alberto José ; Sato, Maria Notomi. / Maternal LAMP/p55gagHIV-1 DNA immunization induces in Utero priming and a long-lasting immune response in vaccinated neonates. In: PLoS One. 2012 ; Vol. 7, No. 2.
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