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.

Low doses of IgG from atopic individuals can modulatein vitroIFN-γ production by human intra-thymic TCD4 and TCD8 cells: An IVIg comparative approach

“…Moreover, we used a commercial procedure to purify IgG that has been widely used to evaluate the effects of IgG in vitro and in vivo by our and other groups. 14,[37][38][39][40][41] Furthermore, as it is possible that this phenomenon occurs in vivo, we can hypothesize that a child born of an atopic mother could be influenced during its gestational period to promote the maturation of T cells with impaired IFN-g responses, which may favor their development into Th2 cells and allergy development. It is important to highlight that as our observations are unprecedented in the literature, the validation and relevance of our hypothesis must be corroborated with in vivo evidence from future studies.…”

LAMP-1 Chimeric to HIV-1 p55Gag in the Immunization of Neonate Mice Induces an Early Germinal Center Formation and AID Expression

“…Our previous studies demonstrated that the LAMP/Gag DNA vaccine is immunogenic in BALB/c neonate mice, and it is also capable of increasing the cellular and humoral Gag-specific response, as well as a long-term response when compared to the vaccine that encodes the Gag protein alone [14]. Maternal LAMP/Gag DNA immunization interferes with the effect of LAMP/Gag in offspring, but it does not inhibit it; also, it is able to prime offspring in the uterus [15]. In addition, the LAMP/Gag DNA mucosal vaccination of neonatal mice is correlated with a strong cellular and humoral anti-Gag response [16].…”

Enhanced immunogenicity and protective efficacy in mice following a Zika DNA vaccine designed by modulation of membrane-anchoring regions and its association to adjuvants

“…LAMP-based DNA vaccines have been broadly described for several viruses (18,(21)(22)(23)(24)(25)(26), being capable of promoting strong antibody response. While LAMP-based DNA vaccines achieve high immunogenicity by promoting antigen processing and presentation through MHC-II, the proper B cell stimulation often requires the recognition of key epitopes that are only available in the context of the folded protein.…”