Abstract

A lack of neutralizing antibodies distinguishes HIV-1 from most other viral pathogens and is responsible to a large degree for the ability of HIV-1 to maintain a persistent infection. A few monoclonal antibodies have been isolated that are broadly neutralizing. We have used X-ray crystallography to investigate the epitopes of broadly neutralizing antibodies and their mechanisms of neutralization. In particular, we have examined CD4-induced (CD4i) antibodies that recognize the coreceptor-binding site, membrane-proximal-binding antibodies like 2F5, CD4-binding-site antibodies like b12, and quaternary specific antibodies like 2909. The b12 analysis lead to the identification of a site of vulnerability to neutralizing antibody on HIV-1, which we are now pursuing as a prime vaccine target.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI005022-08
Application #
7964824
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2009
Total Cost
$169,604
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Zhou, Tongqing; Zheng, Anqi; Baxa, Ulrich et al. (2018) A Neutralizing Antibody Recognizing Primarily N-Linked Glycan Targets the Silent Face of the HIV Envelope. Immunity 48:500-513.e6
González, Nuria; McKee, Krisha; Lynch, Rebecca M et al. (2018) Characterization of broadly neutralizing antibody responses to HIV-1 in a cohort of long term non-progressors. PLoS One 13:e0193773
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
Wang, Lingshu; Shi, Wei; Chappell, James D et al. (2018) Importance of neutralizing monoclonal antibodies targeting multiple antigenic sites on MERS-CoV Spike to avoid neutralization escape. J Virol :
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
Shivatare, Vidya S; Shivatare, Sachin S; Lee, Chang-Chun David et al. (2018) Unprecedented Role of Hybrid N-Glycans as Ligands for HIV-1 Broadly Neutralizing Antibodies. J Am Chem Soc 140:5202-5210
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
Xu, Ling; Pegu, Amarendra; Rao, Ercole et al. (2017) Trispecific broadly neutralizing HIV antibodies mediate potent SHIV protection in macaques. Science 358:85-90
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
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

Showing the most recent 10 out of 84 publications