Broadly neutralizing anti-HIV antibodies

Section of the binding of the antibody VRC01 (green, amino acids D457, S365) to HIV-1 GP120 (purple, N58, Y59) via a water molecule

Binding of the antibody b12 (green) to HIV-1 GP120 (red, contact area in yellow)

Breitneutralisierende anti-HIV antibody ( English broadly neutralizing anti-HIV antibodies , bNAbs) are against several HIV effective strains neutralizing antibodies .

properties

Most neutralizing antibodies are specific for a strain in their neutralizing effect. Broadly neutralizing antibodies bind to conserved areas on the surface of proteins on the virus surface. The generation of broadly neutralizing anti-HIV antibodies is a goal of HIV vaccine design . Broadly neutralizing anti-HIV antibodies are listed in the online databases bNAber and LANL Antibody database . The neutralization effect is dependent both on the binding of the bNAb to viral proteins and on the efficient binding of the bNAb to the Fc receptor . An efficient binding to the FcRn ( isoform of the Fc receptor), which occurs vaginally and rectally, can intensify the neutralization at the entry point of HIV.

Broadly neutralizing anti-HIV antibodies can be subdivided according to their binding site. B. to the part of the GP41 ( membrane-proximal external region , MPER) adjoining the transmembrane domain , to the peptidoglycan layer of the GP120, to the binding site of GP120 for the cellular receptor CD4 or to the variable regions of the GP120 (V1–3) respectively.

Properties of various anti-HIV-1 bNAbs
Viral epitope	Antibody binding	Antibody designation	Year of publication
MPER of the gp41	Sequence epitope	2F5	1992
	Sequence epitope	4E10	1994
	Sequence epitope	M66.6	2011
	Sequence epitope	CAP206-CH12	2011
	Sequence epitope	10E8 l	2012
V1V2-glycan	Peptidoglycan	PG9, PG16	2009
	Peptidoglycan	CH01-04	2011
	Peptidoglycan	PGT 141-145	2011
Outer domain glycan	Glycan only	2G12	1994
V3-glycan	Peptidoglycan	PGT121-123	2011
	Peptidoglycan	PGT125-131	2011
	Peptidoglycan	PGT135-137	2011
CD4 binding site	CDRH3 loop	b12	1991
		HY16	2010
	CDRH3 loop	CH103-106	2013
	is similar to CD4 via CDRH2	VRC01-03	2010
	is similar to CD4 via CDRH2	VRC-PG04, 04b	2011
	is similar to CD4 via CDRH2	VRC-CH30-34	2011
		3BNC117, 3BNC60	2011
	is similar to CD4 via CDRH2	NIH45-46	2011
		12A12, 12A21	2011
		8ANC131, 134	2011
		1NC9, 1B2530	2011

literature

KA Finton, D. Friend, J. Jaffe, M. Gewe, MA Holmes, HB Larman, A. Stuart, K. Larimore, PD Greenberg, SJ Elledge, L. Stamatatos, RK Strong: Ontogeny of Recognition Specificity and Functionality for the Broadly Neutralizing Anti-HIV Antibody 4E10. In: PLoS Pathogens . Volume 10, number 9, September 2014, p. E1004403, ISSN 1553-7374 , doi : 10.1371 / journal.ppat.1004403 , PMID 25254371 , PMC 4177983 (free full text).
J. Mata-Fink, B. Kriegsman, HX Yu, H. Zhu, MC Hanson, DJ Irvine, KD Wittrup: Rapid conformational epitope mapping of anti-gp120 antibodies with a designed mutant panel displayed on yeast. In: Journal of Molecular Biology . Volume 425, number 2, January 2013, ISSN 1089-8638 , pp. 444-456, doi : 10.1016 / j.jmb.2012.11.010 , PMID 23159556 , PMC 3785227 (free full text).
H. Mouquet: Antibody B cell responses in HIV-1 infection. In: Trends in Immunology . [Electronic publication before printing] September 2014, ISSN 1471-4981 , doi : 10.1016 / j.it.2014.08.007 , PMID 25240985 .

Web links

Individual evidence

↑ KA Hassapis, LG Kostrikis: HIV-1 vaccine strategies Utilizing viral vectors Including antigen- Displayed inoviral vectors. In: Current HIV Research . Volume 11, Number 8, December 2013, ISSN 1873-4251 , pp. 610-622, PMID 24517188 .
↑ AM Eroshkin, A. LeBlanc, D. Weekes, K. Post, Z. Li, A. Rajput, ST Butera, DR Burton, A. Godzik: bNAber: database of broadly neutralizing HIV antibodies. In: Nucleic Acids Research . Volume 42, Database issue January 2014, pp. D1133 – D1139, ISSN 1362-4962 , doi : 10.1093 / nar / gkt1083 , PMID 24214957 , PMC 3964981 (free full text).
↑ S. Bournazos, F. Klein, J. Pietzsch, MS Seaman, Nussenzweig MC, JV Ravetch: Broadly neutralizing anti-HIV-1 antibodies require Fc effector functions for in vivo activity. In: Cell . Volume 158, number 6, September 2014, ISSN 1097-4172 , pp. 1243-1253, doi : 10.1016 / j.cell.2014.08.023 , PMID 25215485 , PMC 4167398 (free full text).
^ SY Ko, A. Pegu, RS Rudicell, ZY Yang, MG Joyce, X. Chen, K. Wang, S. Bao, TD Kraemer, T. Rath, M. Zeng, SD Schmidt, JP Todd, SR Penzak, KO Saunders, MC Nason, AT Haase, SS Rao, RS Blumberg, JR Mascola, GJ Nabel: Enhanced neonatal Fc receptor function improves protection against primate SHIV infection. In: Nature . Volume 514, number 7524, October 2014, ISSN 1476-4687 , pp. 642-645, doi : 10.1038 / nature13612 , PMID 25119033 .
^ PN Reardon, H. Sage, SM Dennison, JW Martin, BR Donald, SM Alam, BF Haynes, LD Spicer: Structure of an HIV-1-neutralizing antibody target, the lipid-bound gp41 envelope membrane proximal region trimer. In: Proceedings of the National Academy of Sciences of the United States of America . Volume 111, Number 4, January 2014, pp. 1391-1396, ISSN 1091-6490 . doi : 10.1073 / pnas.1309842111 . PMID 24474763 . PMC 3910588 (free full text).
↑ HX Liao, R. Lynch, T. Zhou, F. Gao, SM Alam, SD Boyd, AZ Fire, KM Roskin, CA Schramm, Z. Zhang, J. Zhu, L. Shapiro, JC Mullikin, S. Gnanakaran, P. Hraber, K. Wiehe, G. Kelsoe, G. Yang, SM Xia, DC Montefiori, R. Parks, KE Lloyd, RM Scearce, KA Soderberg, M. Cohen, G. Kamanga, MK Louder, LM Tran, Y Chen, F. Cai, S. Chen, S. Moquin, X. Du, MG Joyce, S. Srivatsan, B. Zhang, A. Zheng, GM Shaw, BH Hahn, TB Kepler, BT Korber, PD Kwong, JR Mascola, BF Ha: Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. In: Nature. Volume 496, Number 7446, April 2013, pp. 469-476, ISSN 1476-4687 . doi : 10.1038 / nature12053 . PMID 23552890 . PMC 3637846 (free full text).
↑ X. Wu, ZY Yang, Y. Li, CM Hogerkorp, WR Schief, MS Seaman, T. Zhou, SD Schmidt, L. Wu, L. Xu, NS Longo, K. McKee, S. O'Dell, MK Louder, DL Wycuff, Y. Feng, M. Nason, N. Doria-Rose, M. Connors, PD Kwong, M. Roederer, RT Wyatt, GJ Nabel, JR Mascola: Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. In: Science Volume 329, Number 5993, August 2010, pp. 856-861, ISSN 1095-9203 . doi : 10.1126 / science.1187659 . PMID 20616233 . PMC 2965066 (free full text).
↑ T. Zhou, I. Georgiev, X. Wu, ZY Yang, K. Dai, A. Finzi, YD Kwon, JF Scheid, W. Shi, L. Xu, Y. Yang, J. Zhu, MC Nussenzweig, J Sodroski, L. Shapiro, GJ Nabel, JR Mascola, PD Kwong: Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. In: Science Volume 329, Number 5993, August 2010, pp. 811-817, ISSN 1095-9203 . doi : 10.1126 / science.1192819 . PMID 20616231 . PMC 2981354 (free full text).
↑ LM Walker, SK Phogat, PY Chan-Hui, D. Wagner, P. Phung, JL Goss, T. Wrin, MD Simek, S. Fling, JL Mitcham, JK Lehrman, FH Priddy, OA Olsen, SM Frey, PW Hammond, S. Kaminsky, T. Zamb, M. Moyle, WC Koff, P. Poignard, DR Bu: Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. In: Science Volume 326, Number 5950, October 2009, pp. 285-289, ISSN 1095-9203 . doi : 10.1126 / science.1178746 . PMID 19729618 . PMC 3335270 (free full text).
↑ JR Mascola, BF Haynes: HIV-1 neutralizing antibodies: understanding nature's pathways. In: Immunological Reviews . Volume 254, number 1, July 2013, ISSN 1600-065X , pp. 225-244, doi : 10.1111 / imr.12075 , PMID 23772623 , PMC 3738265 (free full text).

[1] KA Hassapis, LG Kostrikis: HIV-1 vaccine strategies Utilizing viral vectors Including antigen- Displayed inoviral vectors. In: Current HIV Research . Volume 11, Number 8, December 2013, ISSN 1873-4251 , pp. 610-622, PMID 24517188 .

[2] AM Eroshkin, A. LeBlanc, D. Weekes, K. Post, Z. Li, A. Rajput, ST Butera, DR Burton, A. Godzik: bNAber: database of broadly neutralizing HIV antibodies. In: Nucleic Acids Research . Volume 42, Database issue January 2014, pp. D1133 – D1139, ISSN 1362-4962 , doi : 10.1093 / nar / gkt1083 , PMID 24214957 , PMC 3964981 (free full text).

[3] S. Bournazos, F. Klein, J. Pietzsch, MS Seaman, Nussenzweig MC, JV Ravetch: Broadly neutralizing anti-HIV-1 antibodies require Fc effector functions for in vivo activity. In: Cell . Volume 158, number 6, September 2014, ISSN 1097-4172 , pp. 1243-1253, doi : 10.1016 / j.cell.2014.08.023 , PMID 25215485 , PMC 4167398 (free full text).

[4] SY Ko, A. Pegu, RS Rudicell, ZY Yang, MG Joyce, X. Chen, K. Wang, S. Bao, TD Kraemer, T. Rath, M. Zeng, SD Schmidt, JP Todd, SR Penzak, KO Saunders, MC Nason, AT Haase, SS Rao, RS Blumberg, JR Mascola, GJ Nabel: Enhanced neonatal Fc receptor function improves protection against primate SHIV infection. In: Nature . Volume 514, number 7524, October 2014, ISSN 1476-4687 , pp. 642-645, doi : 10.1038 / nature13612 , PMID 25119033 .

[5] PN Reardon, H. Sage, SM Dennison, JW Martin, BR Donald, SM Alam, BF Haynes, LD Spicer: Structure of an HIV-1-neutralizing antibody target, the lipid-bound gp41 envelope membrane proximal region trimer. In: Proceedings of the National Academy of Sciences of the United States of America . Volume 111, Number 4, January 2014, pp. 1391-1396, ISSN 1091-6490 . doi : 10.1073 / pnas.1309842111 . PMID 24474763 . PMC 3910588 (free full text).

[6] HX Liao, R. Lynch, T. Zhou, F. Gao, SM Alam, SD Boyd, AZ Fire, KM Roskin, CA Schramm, Z. Zhang, J. Zhu, L. Shapiro, JC Mullikin, S. Gnanakaran, P. Hraber, K. Wiehe, G. Kelsoe, G. Yang, SM Xia, DC Montefiori, R. Parks, KE Lloyd, RM Scearce, KA Soderberg, M. Cohen, G. Kamanga, MK Louder, LM Tran, Y Chen, F. Cai, S. Chen, S. Moquin, X. Du, MG Joyce, S. Srivatsan, B. Zhang, A. Zheng, GM Shaw, BH Hahn, TB Kepler, BT Korber, PD Kwong, JR Mascola, BF Ha: Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. In: Nature. Volume 496, Number 7446, April 2013, pp. 469-476, ISSN 1476-4687 . doi : 10.1038 / nature12053 . PMID 23552890 . PMC 3637846 (free full text).

[7] X. Wu, ZY Yang, Y. Li, CM Hogerkorp, WR Schief, MS Seaman, T. Zhou, SD Schmidt, L. Wu, L. Xu, NS Longo, K. McKee, S. O'Dell, MK Louder, DL Wycuff, Y. Feng, M. Nason, N. Doria-Rose, M. Connors, PD Kwong, M. Roederer, RT Wyatt, GJ Nabel, JR Mascola: Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. In: Science Volume 329, Number 5993, August 2010, pp. 856-861, ISSN 1095-9203 . doi : 10.1126 / science.1187659 . PMID 20616233 . PMC 2965066 (free full text).

[8] T. Zhou, I. Georgiev, X. Wu, ZY Yang, K. Dai, A. Finzi, YD Kwon, JF Scheid, W. Shi, L. Xu, Y. Yang, J. Zhu, MC Nussenzweig, J Sodroski, L. Shapiro, GJ Nabel, JR Mascola, PD Kwong: Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. In: Science Volume 329, Number 5993, August 2010, pp. 811-817, ISSN 1095-9203 . doi : 10.1126 / science.1192819 . PMID 20616231 . PMC 2981354 (free full text).

[9] LM Walker, SK Phogat, PY Chan-Hui, D. Wagner, P. Phung, JL Goss, T. Wrin, MD Simek, S. Fling, JL Mitcham, JK Lehrman, FH Priddy, OA Olsen, SM Frey, PW Hammond, S. Kaminsky, T. Zamb, M. Moyle, WC Koff, P. Poignard, DR Bu: Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. In: Science Volume 326, Number 5950, October 2009, pp. 285-289, ISSN 1095-9203 . doi : 10.1126 / science.1178746 . PMID 19729618 . PMC 3335270 (free full text).

[10] JR Mascola, BF Haynes: HIV-1 neutralizing antibodies: understanding nature's pathways. In: Immunological Reviews . Volume 254, number 1, July 2013, ISSN 1600-065X , pp. 225-244, doi : 10.1111 / imr.12075 , PMID 23772623 , PMC 3738265 (free full text).