Maternal LAMP/p55gagHIV-1 DNA Immunization Induces In Utero Priming and a Long-Lasting Immune Response in Vaccinated Neonates

Author(s)

Rigato, Paula Ordonhez ^[1] ; Maciel, Jr., Milton ^[2] ; Goldoni, Adriana Leticia ^[1] ; Piubelli, Orlando Guerra ^[1] ; Orii, Noemia Mie ^[1] ; Marques, Ernesto Torres ^[3] ; August, Joseph Thomas ^[4] ; da Silva Duarte, Alberto Jose ^[1] ; Sato, Maria Notomi ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Med, Lab Dermatol & Immunodeficiencies, Dept Dermatol, LIM 56, Sao Paulo - Brazil

^[2] USN, Enter Dis Dept, Infect Dis Directorate, Med Res Ctr, Silver Spring, MD - USA

^[3] Ctr Vaccine Res, Dept Infect Dis & Microbiol, Pittsburgh, PA - USA

^[4] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 - USA

• Document type: Journal article
• Source: PLoS One; v. 7, n. 2 FEB 15 2012.
• Web of Science Citations: 5

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-gamma-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. (AU)