Abstract

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-dominant regions;and (2) towards specific target epitopes. Such rationally designed immunogens are thus expected to enable the elicitation of broadly neutralizing antibodies capable of neutralizing a diverse range of HIV-1 isolates.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Scientific Cores Intramural Research (ZIC)
Project #
1ZICAI005114-05
Application #
8946619
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Xu, Kai; Acharya, Priyamvada; Kong, Rui et al. (2018) Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1. Nat Med 24:857-867
Rutten, Lucy; Lai, Yen-Ting; Blokland, Sven et al. (2018) A Universal Approach to Optimize the Folding and Stability of Prefusion-Closed HIV-1 Envelope Trimers. Cell Rep 23:584-595
Kwon, Young D; Chuang, Gwo-Yu; Zhang, Baoshan et al. (2018) Surface-Matrix Screening Identifies Semi-specific Interactions that Improve Potency of a Near Pan-reactive HIV-1-Neutralizing Antibody. Cell Rep 22:1798-1809
Dingens, Adam S; Acharya, Priyamvada; Haddox, Hugh K et al. (2018) Complete functional mapping of infection- and vaccine-elicited antibodies against the fusion peptide of HIV. PLoS Pathog 14:e1007159
Kisalu, Neville K; Idris, Azza H; Weidle, Connor et al. (2018) A human monoclonal antibody prevents malaria infection by targeting a new site of vulnerability on the parasite. Nat Med 24:408-416
Kwong, Peter D; Mascola, John R (2018) HIV-1 Vaccines Based on Antibody Identification, B Cell Ontogeny, and Epitope Structure. Immunity 48:855-871
Alam, S Munir; Aussedat, Baptiste; Vohra, Yusuf et al. (2017) Mimicry of an HIV broadly neutralizing antibody epitope with a synthetic glycopeptide. Sci Transl Med 9:
Kwong, Peter D (2017) What Are the Most Powerful Immunogen Design Vaccine Strategies? A Structural Biologist's Perspective. Cold Spring Harb Perspect Biol :
Hwang, Joyce K; Wang, Chong; Du, Zhou et al. (2017) Sequence intrinsic somatic mutation mechanisms contribute to affinity maturation of VRC01-class HIV-1 broadly neutralizing antibodies. Proc Natl Acad Sci U S A 114:8614-8619
Zhou, Tongqing; Doria-Rose, Nicole A; Cheng, Cheng et al. (2017) Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation. Cell Rep 19:719-732

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