title: Maternal LAMP/p55gagHIV-1 DNA immunization induces in utero priming and a long-lasting immune response in vaccinated neonates.
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.
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Medical School, University of São Paulo, 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 Guerra
authors.initials: OG
authors.lastname: Piubelli
authors.forename: Noemia Mie
authors.initials: NM
authors.lastname: Orii
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: D000653:Amniotic Fluid / Q000737:chemistry; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D000914:Antibodies, Viral / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005333:Fetus / Q000276:immunology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D007111:Immunity, Cellular / Q000502:physiology*; D007114:Immunization; D016130:Immunophenotyping; D051907:Lysosomal Membrane Proteins / Q000235:genetics*; D051379:Mice; D008895:Milk, Human / Q000737:chemistry; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D011498:Protein Precursors / Q000235:genetics*; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D014599:Uterus / Q000276:immunology* / Q000821:virology; D019444:Vaccines, DNA / Q000008:administration & dosage*; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D000914:Antibodies, Viral; D051907:Lysosomal Membrane Proteins; D011498:Protein Precursors; D019444:Vaccines, DNA; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1; C059767:p55 gag precursor protein, Human immunodeficiency virus 1