Antibodies repertoire profile of HIV-infected pregnant women and newborns using the VirScan PhIP-Seq technique

• Grant number: 24/13203-1
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: November 15, 2024
• End date: November 14, 2025
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Maria Notomi Sato
• Grantee: Emanuella Sarmento Alho de Sousa
• Supervisor: Thushan de Silva
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Sheffield, England
• Associated to the scholarship: 22/06074-5 - Maternal-fetal interface: profile of placental microRNAs and maternal and newborn serum exosomes in HIV-1 infection, BP.DR

Abstract

During pregnancy, the transfer of factors and antibodies across the placenta is essential to provide protection to the baby. However, there is limited knowledge regarding the antibody repertoire of pregnant women, especially in pregnant women infected with HIV, under antiretroviral treatment. This study aims to comprehensively evaluate the repertoire of antibodies against all viruses in pregnant women infected with HIV and the transfer of these antibodies to the fetus during pregnancy. Using viral peptidome library VirScan PhIP-Seq technology, we will perform a screening of antibodies against all viruses that have tropism for humans in HIV-infected pregnant women, and uninfected, and their newborns. We will use blood samples that were collected from pregnant women and umbilical cord blood at CAISM - UNICAMP. The VirScan library will be amplified and cloned into a T7 bacteriophage display vector. Serologic assays will involve incubating immunoglobulin from serum samples with the phage library. PCR will be performed for amplification and samples will be barcoded for high-throughput DNA sequencing. Bioinformatics analysis will be conducted using the Bowtie package to obtain read counts and a zero-inflated generalized Poisson model will be performed for calculating the statistical significance of peptide enrichment. This project proposes to identify antibodies generated by HIV as well as other viruses, assessing which antibodies transfer through the FcRn mother to fetus, and evaluating the antibody repertoire in both HIV-infected and uninfected women. With these findings we expect to understand the importance of antibody repertoire of women during pregnancy in the context of HIV infection and its effect on fetal development and on the newborn's immune response.