Significant progress has been made in the rational design of immunogens for an HIV vaccine. Atomic-level structures of viral surface proteins in key functional states, or in complex with neutralizing antibodies, reveal important viral epitopes, providing targets for antibody elicitation. Structure-based computational methods can increase the efficiency, accuracy, and likelihood of success for immunogen design efforts. Specifically, through structural analysis, manipulation, and redesign, we expect a variety of computational techniques to be applied to generate immunogens that focus the immune response (1) away from undesirably immuno-prominent regions and (2) towards specific target epitopes. Such rationally designed immunogens are thus expect to enable the elicitation of broadly neutralizing antibodies that neutralize a diverse range of HIV-1 isolates.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2012
Total Cost
$99,000
Indirect Cost
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State
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Zip Code
Kwon, Young D; Georgiev, Ivelin S; Ofek, Gilad et al. (2016) Optimization of the Solubility of HIV-1-Neutralizing Antibody 10E8 through Somatic Variation and Structure-Based Design. J Virol 90:5899-914
Bonsignori, Mattia; Zhou, Tongqing; Sheng, Zizhang et al. (2016) Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody. Cell 165:449-63
Gorman, Jason; Soto, Cinque; Yang, Max M et al. (2016) Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design. Nat Struct Mol Biol 23:81-90
Joyce, M Gordon; Zhang, Baoshan; Ou, Li et al. (2016) Iterative structure-based improvement of a fusion-glycoprotein vaccine against RSV. Nat Struct Mol Biol 23:811-20
Doria-Rose, Nicole A; Bhiman, Jinal N; Roark, Ryan S et al. (2016) New Member of the V1V2-Directed CAP256-VRC26 Lineage That Shows Increased Breadth and Exceptional Potency. J Virol 90:76-91
Joyce, M Gordon; Wheatley, Adam K; Thomas, Paul V et al. (2016) Vaccine-Induced Antibodies that Neutralize Group 1 and Group 2 Influenza A Viruses. Cell 166:609-23
Kong, Rui; Xu, Kai; Zhou, Tongqing et al. (2016) Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody. Science 352:828-33
Pegu, Amarendra; Asokan, Mangaiarkarasi; Wu, Lan et al. (2015) Activation and lysis of human CD4 cells latently infected with HIV-1. Nat Commun 6:8447
Asokan, M; Rudicell, R S; Louder, M et al. (2015) Bispecific Antibodies Targeting Different Epitopes on the HIV-1 Envelope Exhibit Broad and Potent Neutralization. J Virol 89:12501-12
Kwon, Young Do; Pancera, Marie; Acharya, Priyamvada et al. (2015) Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env. Nat Struct Mol Biol 22:522-31

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