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Interrogating human immune response to vaccination


EMSL Project ID
51120

Abstract

The goal for HIV-1 vaccine design is to induce HIV-1–reactive broadly neutralizing antibodies (bnAbs). In this study we are focused on eliciting antibodies that target the binding site of the CD4 receptor on the HIV-1 Envelope (Env). The CH235-lineage of antibodies targets the CD4-binding site. Cryo-EM structure of the CH235 unmutated common ancestor (UCA) bound to an Env immunogen reveal its binding angle and the contacts it makes with the immunogen. This Env immunogen was injected into monkeys with the goal of eliciting CH235-like antibodies. Our preliminary data reveals similar properties of the antibody as was observed for CH235 UCA suggesting that the elicited antibody mimics CH235 UCA. Here we propose to interrogate the elicited immune response by determining the structure of the elicited antibody in complex with the Env immunogen.

Expectations and Impact on the Field. The cryo-EM structure of the Env immunogen in complex with the vaccine-elicited antibody will determine if the angle of approach and the contacts of the elicited antibody mimic that of CH235 UCA. This will provide critical feedback to the vaccine development program and determine its next steps.

Project Details

Start Date
2019-10-15
End Date
2020-01-22
Status
Closed

Team

Principal Investigator

Priyamvada Acharya
Institution
Duke University

Team Members

Theo Humphreys
Institution
Oregon Health & Science University