DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Competitive exclusion by autologous antibodies can prevent broad HIV-1 antibodies from arising

Abstract

The past decade has seen the discovery of numerous broad and potent monoclonal antibodies against HIV type 1 (HIV-1). Eliciting these antibodies via vaccination appears to be remarkably difficult, not least because they arise late in infection and are highly mutated relative to germline antibody sequences. Here, using a computational model, we show that broad antibodies could in fact emerge earlier and be less mutated, but that they may be prevented from doing so as a result of competitive exclusion by the autologous antibody response. We further find that this competitive exclusion is weaker in infections founded by multiple distinct strains, with broadly neutralizing antibodies emerging earlier than in infections founded by a single strain. Our computational model simulates coevolving multitype virus and antibody populations. Broadly neutralizing antibodies may therefore be easier for the adaptive immune system to generate than previously thought. As a result, if less mutated broad antibodies exist, it may be possible to elicit them with a vaccine containing a mixture of diverse virus strains.

Authors:
 [1];  [2]
  1. Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545,, Center for Nonlinear Systems, Los Alamos National Laboratory, Los Alamos, NM 87545
  2. Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545,
Publication Date:
Research Org.:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1579280
Alternate Identifier(s):
OSTI ID: 1233530
Report Number(s):
LA-UR-15-21719
Journal ID: ISSN 0027-8424
Grant/Contract Number:  
AC52-06NA25396; R01-AI028433; R01-OD011095; UM1-AI100645
Resource Type:
Published Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 112 Journal Issue: 37; Journal ID: ISSN 0027-8424
Publisher:
Proceedings of the National Academy of Sciences
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; human immunodeficiency virus; broadly neutralizing antibodies; coevolutionary dynamics; mathematical modeling; competitive exclusion

Citation Formats

Luo, Shishi, and Perelson, Alan S. Competitive exclusion by autologous antibodies can prevent broad HIV-1 antibodies from arising. United States: N. p., 2015. Web. doi:10.1073/pnas.1505207112.
Luo, Shishi, & Perelson, Alan S. Competitive exclusion by autologous antibodies can prevent broad HIV-1 antibodies from arising. United States. https://doi.org/10.1073/pnas.1505207112
Luo, Shishi, and Perelson, Alan S. Mon . "Competitive exclusion by autologous antibodies can prevent broad HIV-1 antibodies from arising". United States. https://doi.org/10.1073/pnas.1505207112.
@article{osti_1579280,
title = {Competitive exclusion by autologous antibodies can prevent broad HIV-1 antibodies from arising},
author = {Luo, Shishi and Perelson, Alan S.},
abstractNote = {The past decade has seen the discovery of numerous broad and potent monoclonal antibodies against HIV type 1 (HIV-1). Eliciting these antibodies via vaccination appears to be remarkably difficult, not least because they arise late in infection and are highly mutated relative to germline antibody sequences. Here, using a computational model, we show that broad antibodies could in fact emerge earlier and be less mutated, but that they may be prevented from doing so as a result of competitive exclusion by the autologous antibody response. We further find that this competitive exclusion is weaker in infections founded by multiple distinct strains, with broadly neutralizing antibodies emerging earlier than in infections founded by a single strain. Our computational model simulates coevolving multitype virus and antibody populations. Broadly neutralizing antibodies may therefore be easier for the adaptive immune system to generate than previously thought. As a result, if less mutated broad antibodies exist, it may be possible to elicit them with a vaccine containing a mixture of diverse virus strains.},
doi = {10.1073/pnas.1505207112},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 37,
volume = 112,
place = {United States},
year = {Mon Aug 31 00:00:00 EDT 2015},
month = {Mon Aug 31 00:00:00 EDT 2015}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1073/pnas.1505207112

Citation Metrics:
Cited by: 38 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

The HIV-1 Envelope Glycoproteins: Fusogens, Antigens, and Immunogens
journal, June 1998


Limited Neutralizing Antibody Specificities Drive Neutralization Escape in Early HIV-1 Subtype C Infection
journal, September 2009


Germinal Centers
journal, April 2012


Manipulating the Selection Forces during Affinity Maturation to Generate Cross-Reactive HIV Antibodies
journal, February 2015


Independent Expansion of Epitope-Specific Plasma Cell Responses upon HIV-1 Envelope Glycoprotein Immunization
journal, June 2013

  • Forsell, Mattias N. E.; Soldemo, Martina; Dosenovic, Pia
  • The Journal of Immunology, Vol. 191, Issue 1
  • DOI: 10.4049/jimmunol.1203087

Global Panel of HIV-1 Env Reference Strains for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies
journal, December 2013

  • deCamp, A.; Hraber, P.; Bailer, R. T.
  • Journal of Virology, Vol. 88, Issue 5
  • DOI: 10.1128/JVI.02853-13

Sequential Immunization with a Subtype B HIV-1 Envelope Quasispecies Partially Mimics the In Vivo Development of Neutralizing Antibodies
journal, March 2011

  • Malherbe, D. C.; Doria-Rose, N. A.; Misher, L.
  • Journal of Virology, Vol. 85, Issue 11
  • DOI: 10.1128/JVI.02419-10

Computational Models of B cell and T cell Receptors
book, January 2007


HIV-1 neutralizing antibodies: understanding nature's pathways
journal, June 2013

  • Mascola, John R.; Haynes, Barton F.
  • Immunological Reviews, Vol. 254, Issue 1
  • DOI: 10.1111/imr.12075

Simulation of B Cell Affinity Maturation Explains Enhanced Antibody Cross-Reactivity Induced by the Polyvalent Malaria Vaccine AMA1
journal, July 2014

  • Chaudhury, Sidhartha; Reifman, Jaques; Wallqvist, Anders
  • The Journal of Immunology, Vol. 193, Issue 5
  • DOI: 10.4049/jimmunol.1401054

The Antibody Response against HIV-1
journal, November 2011


Rational Design of Vaccines to Elicit Broadly Neutralizing Antibodies to HIV-1
journal, September 2011

  • Kwong, P. D.; Mascola, J. R.; Nabel, G. J.
  • Cold Spring Harbor Perspectives in Medicine, Vol. 1, Issue 1
  • DOI: 10.1101/cshperspect.a007278

Lessons in Nonhuman Primate Models for AIDS Vaccine Research: From Minefields to Milestones
journal, March 2012


Predicting the size of the T-cell receptor and antibody combining region from consideration of efficient self-nonself discrimination.
journal, March 1993

  • Percus, J. K.; Percus, O. E.; Perelson, A. S.
  • Proceedings of the National Academy of Sciences, Vol. 90, Issue 5
  • DOI: 10.1073/pnas.90.5.1691

Deriving Shape Space Parameters from Immunological Data
journal, November 1997

  • Smith, Derek J.; Forrest, Stephanie; Hightower, Ron R.
  • Journal of Theoretical Biology, Vol. 189, Issue 2
  • DOI: 10.1006/jtbi.1997.0495

Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection
journal, January 2011

  • Wrammert, Jens; Koutsonanos, Dimitrios; Li, Gui-Mei
  • The Journal of Experimental Medicine, Vol. 208, Issue 1
  • DOI: 10.1084/jem.20101352

Transmission of Single HIV-1 Genomes and Dynamics of Early Immune Escape Revealed by Ultra-Deep Sequencing
journal, August 2010


Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia
journal, October 2013

  • Shingai, Masashi; Nishimura, Yoshiaki; Klein, Florian
  • Nature, Vol. 503, Issue 7475
  • DOI: 10.1038/nature12746

Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys
journal, October 2013

  • Barouch, Dan H.; Whitney, James B.; Moldt, Brian
  • Nature, Vol. 503, Issue 7475
  • DOI: 10.1038/nature12744

Passive transfer of modest titers of potent and broadly neutralizing anti-HIV monoclonal antibodies block SHIV infection in macaques
journal, August 2014

  • Shingai, Masashi; Donau, Olivia K.; Plishka, Ronald J.
  • The Journal of Experimental Medicine, Vol. 211, Issue 10
  • DOI: 10.1084/jem.20132494

B-cell–lineage immunogen design in vaccine development with HIV-1 as a case study
journal, May 2012

  • Haynes, Barton F.; Kelsoe, Garnett; Harrison, Stephen C.
  • Nature Biotechnology, Vol. 30, Issue 5
  • DOI: 10.1038/nbt.2197

Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies
journal, September 2012


Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1
journal, July 2010


Variable efficacy of repeated annual influenza vaccination
journal, November 1999

  • Smith, D. J.; Forrest, S.; Ackley, D. H.
  • Proceedings of the National Academy of Sciences, Vol. 96, Issue 24
  • DOI: 10.1073/pnas.96.24.14001

Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies
journal, March 2014

  • Doria-Rose, Nicole A.; Schramm, Chaim A.; Gorman, Jason
  • Nature, Vol. 509, Issue 7498
  • DOI: 10.1038/nature13036

Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing
journal, August 2011


HIV-1 Fitness Cost Associated with Escape from the VRC01 Class of CD4 Binding Site Neutralizing Antibodies
journal, January 2015

  • Lynch, Rebecca M.; Wong, Patrick; Tran, Lillian
  • Journal of Virology, Vol. 89, Issue 8
  • DOI: 10.1128/JVI.03608-14

Neutralizing antibodies to HIV-1 induced by immunization
journal, February 2013

  • McCoy, Laura E.; Weiss, Robin A.
  • The Journal of Experimental Medicine, Vol. 210, Issue 2
  • DOI: 10.1084/jem.20121827

Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus
journal, April 2013

  • Liao, Hua-Xin; Lynch, Rebecca; Zhou, Tongqing
  • Nature, Vol. 496, Issue 7446
  • DOI: 10.1038/nature12053

Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection
journal, May 2008

  • Keele, B. F.; Giorgi, E. E.; Salazar-Gonzalez, J. F.
  • Proceedings of the National Academy of Sciences, Vol. 105, Issue 21
  • DOI: 10.1073/pnas.0802203105

Early development of broadly neutralizing antibodies in HIV-1–infected infants
journal, May 2014

  • Goo, Leslie; Chohan, Vrasha; Nduati, Ruth
  • Nature Medicine, Vol. 20, Issue 6
  • DOI: 10.1038/nm.3565

HIV Pathogenesis: Dynamics and Genetics of Viral Populations and Infected Cells
journal, January 2013


bNAber: database of broadly neutralizing HIV antibodies
journal, November 2013

  • Eroshkin, Alexey M.; LeBlanc, Andrew; Weekes, Dana
  • Nucleic Acids Research, Vol. 42, Issue D1
  • DOI: 10.1093/nar/gkt1083

B cell responses to HIV-1 infection and vaccination: pathways to preventing infection
journal, February 2011


Structural Basis of Immune Evasion at the Site of CD4 Attachment on HIV-1 gp120
journal, November 2009