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Structural characterization of immunogens in complex with antibodies for structure-based vaccine design


EMSL Project ID
50659

Abstract

Although to-date numerous vaccines exist, their mechanism of protection is not always understood. Additionally, there are pathogens such as HIV and Malaria for which vaccines do not exist. Our research interest is to use structural biology to 1) understand the interactions between the host immune system and pathogens at the molecular level and 2) apply the structure-based vaccine design paradigm to pathogens that cause tremendous health burden and for which vaccines are either not yet available, or can be improved upon, such as HIV-1, malaria, EBV, and others. Although my group has focused on using X-ray crystallography to determine structures of antibodies with antigens, we have started to explore the single particle electron microscopy method (mainly nsEM at this point) and would like to become full time users. Indeed, our current project focuses on obtaining structural information of three proteins from three different pathogens: the Human Immunodeficiency Virus (HIV-1) Envelope glycoproteins, the Human Papilloma Virus (HPV) L1 pentamer and Virus-Like Particle (VLP) and the Circumsporozoite Protein (CSP) from Plasmodium Falciparum, all in complex with matching vaccine-elicited antibodies or antibodies obtained from natural infection. We believe that being able to be trained and having access to this method will accelerate our research goals. These structures will give invaluable information concerning important epitopes that are targeted by the antibodies and could lead to interventions against these pathogens.

Project Details

Start Date
2019-03-15
End Date
2021-03-17
Status
Closed

Team

Principal Investigator

Marie Pancera
Institution
Fred Hutchinson Cancer Research Center

Team Members

Nicholas Hurlburt
Institution
Fred Hutchinson Cancer Research Center

Justas Rodarte
Institution
Fred Hutchinson Cancer Research Center

Safia Aljedani
Institution
Fred Hutchinson Cancer Research Center

Harry Scott
Institution
Oregon Health & Science University

Tyler Liban
Institution
Fred Hutchinson Cancer Research Center

Suruchi Singh
Institution
Fred Hutchinson Cancer Research Center

Irina El Khoury
Institution
Environmental Molecular Sciences Laboratory