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Title: Antibody Light-Chain-Restricted Recognition of the Site of Immune Pressure in the RV144 HIV-1 Vaccine Trial Is Phylogenetically Conserved

Abstract

In HIV-1, the ability to mount antibody responses to conserved, neutralizing epitopes is critical for protection. Here we have studied the light chain usage of human and rhesus macaque antibodies targeted to a dominant region of the HIV-1 envelope second variable (V2) region involving lysine (K) 169, the site of immune pressure in the RV144 vaccine efficacy trial. We found that humans and rhesus macaques used orthologous lambda variable gene segments encoding a glutamic acid-aspartic acid (ED) motif for K169 recognition. Structure determination of an unmutated ancestor antibody demonstrated that the V2 binding site was preconfigured for ED motif-mediated recognition prior to maturation. Thus, light chain usage for recognition of the site of immune pressure in the RV144 trial is highly conserved across species. In conclusion, these data indicate that the HIV-1 K169-recognizing ED motif has persisted over the diversification between rhesus macaques and humans, suggesting an evolutionary advantage of this antibody recognition mode.

Authors:
 [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [2];  [3];  [4];  [3];  [5];  [6];  [7] more »;  [8];  [8];  [1];  [1];  [1];  [1];  [9];  [10];  [1];  [1];  [1];  [1] « less
  1. Duke Univ., Durham, NC (United States). School of Medicine, Human Vaccine Inst.
  2. National Inst. for Communicable Diseases, Johannesburg (South Africa). Centre for the AIDS Programme of Research in South Africa (CAPRISA)
  3. Mahidol Univ., Bangkok (Thailand). Dept. of Tropical Medicine
  4. Armed Forces Research Inst. of Medical Sciences (AFRIMS), Bangkok (Thailand)
  5. Ministry of Public Health, Nonthaburi (Thailand). Dept. of Disease Control
  6. Sanofi Pasteur, Inc., Swiftwater, PA (United States)
  7. Global Solutions for Infectious Diseases, South San Francisco, CA (United States)
  8. Walter Reed Army Inst. of Research, Silver Spring, MD (United States)
  9. Harvard Univ., Cambridge, MA (United States). School of Medicine, Beth Israel Deaconess Medical Center
  10. Boston Univ., MA (United States). Dept. of Microbiology
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); Bill & Melinda Gates Foundation; National Institutes of Health (NIH)
OSTI Identifier:
1233905
Alternate Identifier(s):
OSTI ID: 1227575; OSTI ID: 1258693
Grant/Contract Number:  
W-31-109-Eng-38; P30-AI-64518; 5T32-AI007392; OPP1033098; UMI-AI100645
Resource Type:
Published Article
Journal Name:
Immunity
Additional Journal Information:
Journal Volume: 41; Journal Issue: 6; Journal ID: ISSN 1074-7613
Country of Publication:
United States
Language:
ENGLISH
Subject:
60 APPLIED LIFE SCIENCES

Citation Formats

Wiehe, Kevin, Easterhoff, David, Luo, Kan, Nicely, Nathan I., Bradley, Todd, Jaeger, Frederick H., Dennison, S. Moses, Zhang, Ruijun, Lloyd, Krissey E., Stolarchuk, Christina, Parks, Robert, Sutherland, Laura L., Scearce, Richard M., Morris, Lynn, Kaewkungwal, Jaranit, Nitayaphan, Sorachai, Pitisuttithum, Punnee, Rerks-Ngarm, Supachai, Sinangil, Faruk, Phogat, Sanjay, Michael, Nelson L., Kim, Jerome H., Kelsoe, Garnett, Montefiori, David C., Tomaras, Georgia D., Bonsignori, Mattia, Santra, Sampa, Kepler, Thomas B., Alam, S.  Munir, Moody, M. Anthony, Liao, Hua-Xin, and Haynes, Barton F. Antibody Light-Chain-Restricted Recognition of the Site of Immune Pressure in the RV144 HIV-1 Vaccine Trial Is Phylogenetically Conserved. United States: N. p., 2014. Web. doi:10.1016/j.immuni.2014.11.014.
Wiehe, Kevin, Easterhoff, David, Luo, Kan, Nicely, Nathan I., Bradley, Todd, Jaeger, Frederick H., Dennison, S. Moses, Zhang, Ruijun, Lloyd, Krissey E., Stolarchuk, Christina, Parks, Robert, Sutherland, Laura L., Scearce, Richard M., Morris, Lynn, Kaewkungwal, Jaranit, Nitayaphan, Sorachai, Pitisuttithum, Punnee, Rerks-Ngarm, Supachai, Sinangil, Faruk, Phogat, Sanjay, Michael, Nelson L., Kim, Jerome H., Kelsoe, Garnett, Montefiori, David C., Tomaras, Georgia D., Bonsignori, Mattia, Santra, Sampa, Kepler, Thomas B., Alam, S.  Munir, Moody, M. Anthony, Liao, Hua-Xin, & Haynes, Barton F. Antibody Light-Chain-Restricted Recognition of the Site of Immune Pressure in the RV144 HIV-1 Vaccine Trial Is Phylogenetically Conserved. United States. doi:10.1016/j.immuni.2014.11.014.
Wiehe, Kevin, Easterhoff, David, Luo, Kan, Nicely, Nathan I., Bradley, Todd, Jaeger, Frederick H., Dennison, S. Moses, Zhang, Ruijun, Lloyd, Krissey E., Stolarchuk, Christina, Parks, Robert, Sutherland, Laura L., Scearce, Richard M., Morris, Lynn, Kaewkungwal, Jaranit, Nitayaphan, Sorachai, Pitisuttithum, Punnee, Rerks-Ngarm, Supachai, Sinangil, Faruk, Phogat, Sanjay, Michael, Nelson L., Kim, Jerome H., Kelsoe, Garnett, Montefiori, David C., Tomaras, Georgia D., Bonsignori, Mattia, Santra, Sampa, Kepler, Thomas B., Alam, S.  Munir, Moody, M. Anthony, Liao, Hua-Xin, and Haynes, Barton F. Sat . "Antibody Light-Chain-Restricted Recognition of the Site of Immune Pressure in the RV144 HIV-1 Vaccine Trial Is Phylogenetically Conserved". United States. doi:10.1016/j.immuni.2014.11.014.
@article{osti_1233905,
title = {Antibody Light-Chain-Restricted Recognition of the Site of Immune Pressure in the RV144 HIV-1 Vaccine Trial Is Phylogenetically Conserved},
author = {Wiehe, Kevin and Easterhoff, David and Luo, Kan and Nicely, Nathan I. and Bradley, Todd and Jaeger, Frederick H. and Dennison, S. Moses and Zhang, Ruijun and Lloyd, Krissey E. and Stolarchuk, Christina and Parks, Robert and Sutherland, Laura L. and Scearce, Richard M. and Morris, Lynn and Kaewkungwal, Jaranit and Nitayaphan, Sorachai and Pitisuttithum, Punnee and Rerks-Ngarm, Supachai and Sinangil, Faruk and Phogat, Sanjay and Michael, Nelson L. and Kim, Jerome H. and Kelsoe, Garnett and Montefiori, David C. and Tomaras, Georgia D. and Bonsignori, Mattia and Santra, Sampa and Kepler, Thomas B. and Alam, S.  Munir and Moody, M. Anthony and Liao, Hua-Xin and Haynes, Barton F.},
abstractNote = {In HIV-1, the ability to mount antibody responses to conserved, neutralizing epitopes is critical for protection. Here we have studied the light chain usage of human and rhesus macaque antibodies targeted to a dominant region of the HIV-1 envelope second variable (V2) region involving lysine (K) 169, the site of immune pressure in the RV144 vaccine efficacy trial. We found that humans and rhesus macaques used orthologous lambda variable gene segments encoding a glutamic acid-aspartic acid (ED) motif for K169 recognition. Structure determination of an unmutated ancestor antibody demonstrated that the V2 binding site was preconfigured for ED motif-mediated recognition prior to maturation. Thus, light chain usage for recognition of the site of immune pressure in the RV144 trial is highly conserved across species. In conclusion, these data indicate that the HIV-1 K169-recognizing ED motif has persisted over the diversification between rhesus macaques and humans, suggesting an evolutionary advantage of this antibody recognition mode.},
doi = {10.1016/j.immuni.2014.11.014},
journal = {Immunity},
number = 6,
volume = 41,
place = {United States},
year = {2014},
month = {11}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.1016/j.immuni.2014.11.014

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Cited by: 24 works
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Works referencing / citing this record:

Difficult-to-neutralize global HIV-1 isolates are neutralized by antibodies targeting open envelope conformations
journal, July 2019