Elicitation of antibodies against targets that are immunorecessive, cryptic, or transient in their native context is a challenge for vaccine design. One potential solution is precise immunogen design. The ability of structural biology to provide atomic-level definition of antibody-antigen interactions and of computational biology to manipulate protein structure has raised the possibility at least for protein antigens of precisely replicating the antigenic surface recognized by a target antibody. Recent successes in immunogen design by transplanting an epitope to foreign scaffolds and in focusing the antibody response to a precise site using computational techniques, termed scaffolding/epitope-transplantation and antigenic resurfacing, respectively highlight the notion that computational biology may play a crucial role in vaccine design. Rather than relying on a small set of well-defined tools, however, increasing evidence suggests that vaccine design will require the systematic development of computational algorithms, methods, and tools associated with the analysis, design, of manipulation of protein structures and protein-protein (or protein-ligand) interactions. Here we address a number of technological issues that are expected to impact structure-based vaccine design. Specifically, we describe the development of new protein design and structure-modeling algorithms, methods, and tools that are particularly suited for vaccine design.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2012
Total Cost
$99,000
Indirect Cost
City
State
Country
Zip Code
Kwong, Peter D; Chuang, Gwo-Yu; DeKosky, Brandon J et al. (2017) Antibodyomics: bioinformatics technologies for understanding B-cell immunity to HIV-1. Immunol Rev 275:108-128
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
Chuang, Gwo-Yu; Geng, Hui; Pancera, Marie et al. (2017) Structure-Based Design of a Soluble Prefusion-Closed HIV-1 Env Trimer with Reduced CD4 Affinity and Improved Immunogenicity. J Virol 91:
Sheng, Zizhang; Schramm, Chaim A; Kong, Rui et al. (2017) Gene-Specific Substitution Profiles Describe the Types and Frequencies of Amino Acid Changes during Antibody Somatic Hypermutation. Front Immunol 8:537
Doria-Rose, Nicole A; Altae-Tran, Han R; Roark, Ryan S et al. (2017) Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting. PLoS Pathog 13:e1006148
Clark, Anthony J; Gindin, Tatyana; Zhang, Baoshan et al. (2017) Free Energy Perturbation Calculation of Relative Binding Free Energy between Broadly Neutralizing Antibodies and the gp120 Glycoprotein of HIV-1. J Mol Biol 429:930-947
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; Wheatley, Adam K; Thomas, Paul V et al. (2016) Vaccine-Induced Antibodies that Neutralize Group 1 and Group 2 Influenza A Viruses. Cell 166:609-623
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 23:811-820
Stewart-Jones, Guillaume B E; Soto, Cinque; Lemmin, Thomas et al. (2016) Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G. Cell 165:813-26

Showing the most recent 10 out of 24 publications