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

Proceedings of the National Academy of Sciences of the United States of America
Shishi Luo, Alan S Perelson

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. If less mutated broad antibodies exist, it may be possible to elicit them with a vaccine containing a mixture of diverse virus strains.

References

Mar 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·J K PercusA S Perelson
Feb 28, 1998·Journal of Theoretical Biology·D J SmithA S Perelson
Nov 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·D J SmithA S Perelson
May 21, 2008·Proceedings of the National Academy of Sciences of the United States of America·Brandon F KeeleGeorge M Shaw
Sep 19, 2009·PLoS Pathogens·Penny L MooreUNKNOWN NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI)
Nov 30, 2010·Trends in Molecular Medicine·Barton F HaynesGeorgia D Tomaras
Jan 12, 2011·The Journal of Experimental Medicine·Jens WrammertPatrick C Wilson
Jun 3, 2011·Cold Spring Harbor Protocols·Véronique GiudicelliMarie-Paule Lefranc
Jan 10, 2012·Annual Review of Immunology·Gabriel D Victora, Michel C Nussenzweig
Jan 10, 2012·Cold Spring Harbor Perspectives in Medicine·Peter D KwongGary J Nabel
Feb 9, 2012·Cold Spring Harbor Perspectives in Medicine·Julie Overbaugh, Lynn Morris
May 9, 2012·Nature Biotechnology·Barton F HaynesThomas B Kepler
Jun 8, 2012·Cold Spring Harbor Perspectives in Medicine·Jeffrey D Lifson, Nancy L Haigwood
Jan 4, 2013·Cold Spring Harbor Perspectives in Medicine·John Coffin, Ronald Swanstrom
Feb 13, 2013·The Journal of Experimental Medicine·Laura E McCoy, Robin A Weiss
Apr 5, 2013·Nature·Hua-Xin LiaoBarton F Haynes
Jun 7, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mattias N E ForsellGunilla B Karlsson Hedestam
Jun 19, 2013·Immunological Reviews·John R Mascola, Barton F Haynes
Nov 12, 2013·Nucleic Acids Research·Alexey M EroshkinAdam Godzik
Mar 5, 2014·Nature·Nicole A Doria-RoseJohn R Mascola
May 27, 2014·Nature Medicine·Leslie GooJulie Overbaugh
Aug 1, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sidhartha ChaudhuryAnders Wallqvist

❮ Previous
Next ❯

Citations

Jul 22, 2015·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Shishi Luo, Alan S Perelson
Nov 1, 2016·Nature Medicine·Peter RusertUNKNOWN Swiss HIV Cohort Study
Oct 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·J Scott ShafferArup K Chakraborty
Feb 23, 2017·Annual Review of Immunology·Arup K Chakraborty
Jan 10, 2018·Proceedings of the National Academy of Sciences of the United States of America·Raymond H Y LouieMatthew R McKay
Jan 7, 2017·Reports on Progress in Physics·Arup K Chakraborty, John P Barton
Feb 25, 2018·Journal of Mathematical Biology·Cameron J Browne, Hal L Smith
Dec 15, 2015·Current Opinion in Infectious Diseases·Godelieve J de Bree, Rebecca M Lynch
Mar 5, 2020·Scientific Reports·Samantha ErwinStanca M Ciupe
Sep 13, 2017·Frontiers in Immunology·Esteban A Hernandez-Vargas
Sep 29, 2017·Frontiers in Microbiology·Assaf AmitaiArup K Chakraborty
Nov 28, 2018·Retrovirology·Jelle van Schooten, Marit J van Gils
Aug 5, 2020·Proceedings of the National Academy of Sciences of the United States of America·Kayla G SprengerArup K Chakraborty
Apr 28, 2019·Proceedings of the National Academy of Sciences of the United States of America·Payton A Weidenbacher, Peter S Kim
Jul 31, 2020·Bioinformatics·Gustavo Hernandez-Mejia, Esteban A Hernandez-Vargas
Aug 30, 2019·Current Opinion in Systems Biology·Jessica M Conway, Ruy M Ribeiro
Jan 22, 2021·Physical Biology·Arvind MuruganNigel Goldenfeld

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antibody Specificity

Antibodies produced by B cells are highly specific for antigen as a result of random gene recombination and somatic hypermutation and affinity maturation. As the main effector of the humoral immune system, antibodies can neutralize foreign cells. Find the latest research on antibody specificity here.