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​Gaiha: Multi-networked T cell epitope vaccine for global HIV prevention and therapy

OVERVIEW

Recent findings indicate that successful in vivo control of clade B HIV is achieved by directing functional CD8 + T cell responses towards epitopes derived from topologically important regions of the viral proteome. Highly networked epitopes, which are a subset of sequence-conserved epitopes, could serve as a valuable set of mutation-resistant epitopes for inclusion in a T cell-based vaccine for HIV. CD8+ T cell targeting of highly networked epitopes may distinguish individuals who naturally control HIV, even in the absence of protective HLA alleles. This investment will be used to optimize a T cell-based prophylactic and therapeutic vaccine for HIV that incorporates CD8+ T cell epitopes identified by a structure-based network analysis algorithm. This method utilizes network theory and protein structure data to identify amino acid residues and T cell epitopes of topological importance (and with broad representation in the global population). Epitopes identified using this approach will first be evaluated to determine whether they are preferentially targeted by controllers in a sub-Saharan African cohort. Specifically, the protective nature of highly networked epitopes will be studied in HIV clade C-infected individuals. The design of HLA class I-restricted and HLA-E-restricted CD8+ T cell vaccine candidates composed of highly networked epitopes will then be optimized with the goal of testing immunogenicity in an improved hum​an leukocyte antigen (HLA)-expressing mouse model. These studies will provide critical pre-clinical evidence in support of advancing multi-networked T cell epitope vaccine candidates towards clinical safety and efficacy testing in humans.

RESEARCH OBJECTIVES

The specific goals of this investment are: 

1) Confirm the protective nature of highly networked epitopes in a cohort of HIV clade C-infected individuals from sub-Saharan Africa. 

2) Optimize the development of a multi-networked T cell epitope vaccine candidate. 

3) Evaluate the immunogenicity of a multi-networked T cell epitope vaccine candidate in HLAexpressing mice.

 

Grant at a Glance

Principal Investigator

Gaurav Gaiha, M.D.

Grantee Institution

Massachusetts General Hospital; Boston, USA

Project Title

Multi-networked T cell epitope vaccine for global HIV prevention and therapy

Grant Award

Up to $4.3 million, awarded August 2019

Collaborating Institutions

  • Wistar Institute, Philadelphia, PA


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