Carolina Herrera, Ph.D.
St. George's University of London
Title: "Use of Tissue Explants to Evaluate Mucosal Immune Response in NHP's and Humans"
Description: The HIV vaccine field is dependent upon testing in non-human primates (NHPs) as the only relevant model to study infection. However, the predictive accuracy of NHP studies of efficacy in humans has proven not to be yet validated. To overcome the roadblock to predicting efficacy in human subjects of HIV candidate vaccines tested in nonhuman primates (NHPs), we propose to assess and compare the potency of vaccine induced B-cell dependent mucosal immune responses in mucosal tissue explants and peripheral blood mononuclear cells (PBMCs). These comparisons could represent an important first step towards establishing a bridge between NHP and human studies. This proposal will focus on levels of IgG and IgA elicited after vaccination with ALVAC-HIV (vCP1521) prime and AIDSVAX B/E boost, and their neutralizing activity at mucosal sites of viral entry and systemically. Changes at the genomic level and in the cytokine profile after immunization will also be assessed. This project will allow us to refine the usage of the NHP model, opening the possibility to reduce the number of in vivo challenges, and potentially providing a new surrogate model of mucosal protection that can allow direct cross-validation of NHP and human studies.
Mentors: My mentors are Robin Shattock, Jerome Kim and Ron Veazey. Prof. Shattock is an expert in mucosal HIV transmission and my mentor at St. George's, University of London, where I have been working on the tissue explant model and its applications in the microbicide and vaccine fields for five years. Dr. Kim is my clinical mentor with key expertise HIV molecular epidemiology and HIV vaccine development. Prof. Veazey is a recognized expert on NHP studies and specifically SHIV/SIV mucosal challenge studies in Rhesus macaques, and he is my NHP mentor.