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-binding-site directed antibodies like VRC01, quaternary antibodies like PG9 and PG16, and membrane-proximal-binding antibodies like 2F5. The VRC01 antibody is particularly attractive as it neutralizes over 90% of circulating HIV-1 isolates and appears to be elicited in high titer in 5-10% of HIV-1 infected individuals. The quaternary antibodies are also attractive, as some groups estimate that this is the most commonly elicited broadly neutralizing response.

  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 #
1ZIAAI005022-09
Application #
8148425
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2010
Total Cost
$1,154,380
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