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Institut de Biologie StructuraleGrenoble / France

Presentation of the HIV and Human Persistent Virus group

Group Leader: Pascal Poignard

Presentation

The recent discovery of potent HIV-1 broadly neutralizing antibodies (bnAbs), i.e. able to block the replication of a large fraction of global circulating HIV-1 isolates has bolstered the field of antibody-based HIV vaccine development. A fraction of HIV-1-infected individuals eventually develop potent and broad neutralizing antibody responses, typically within a few years following infection. BnAbs, isolated from such donors, target regions on the viral spike that are highly structurally conserved despite the tremendous global sequence diversity of the HIV-1 Env protein. These regions include the CD4-binding site, the V3 N332 glycan region, a quaternary epitope in the V1/V2 region, the MPER region of gp41, and epitopes at the gp120/gp41 interface.

The elicitation of bnAbs prior to infection would presumably protect against infection by most circulating HIV strains and is considered one of the highest priorities of the HIV vaccine research field. However, to date no candidate vaccine has been found to elicit such responses.

The Poignard team focuses on understanding how broadly antibody responses eventually develop in a subset of HIV-infected donors. The goal is to gain knowledge from natural infection for the further design of effective immunogens and vaccine strategies to prevent HIV infection.

Members

Pascal POIGNARD M.D., Ph.D., PU PH (CHUGA & UGA)

Marlyse BUISSON Ph.D., Scientist (CHUGA)
Sebastian DERGAN DYLON Ph.D., Post doc (ANRS)
Claire ROUSSET Ph.D. student (UGA)
Romy ROUZEAU Ph.D. student (Sidaction)
Diane AUDIFFREN M1R student (UGA)
Audrey CAPPELLETTI Research Associate (UGA)

Sylvie LARRAT Ph.D., MCU PH (CHUGA)
Benjamin NEMOZ Medical resident (CHUGA)

Research topics

  • Viral entry and mechanism of HIV neutralization
  • Neutralizing antibodies in prevention and treatment of HIV infection
  • HIV broadly neutralizing antibodies: coevolution Ab-Env leading to their development

Keywords

Human monoclonal antibodies - Neutralization - HIV - Vaccine

Specialized techniques

  • Human monoclonal antibody isolation
  • Monomeric and trimeric HIV Env production
  • Monoclonal antibody production and purification
  • HIV neutralization assay

Major publications

HIV entry and mechanisms of HIV neutralization

1. Sattentau, Q. J., J. P. Moore, F. Vignaux, F. Traincard and P. Poignard (1993). "Conformational changes induced in the envelope glycoproteins of the human and simian immunodeficiency viruses by soluble receptor binding." J Virol 67(12): 7383-7393.
2. Poignard, P., T. Fouts, D. Naniche, J. P. Moore and Q. J. Sattentau (1996). "Neutralizing antibodies to human immunodeficiency virus type-1 gp120 induce envelope glycoprotein subunit dissociation." J Exp Med 183(2): 473-484.
3. Poignard, P., E. O. Saphire, P. W. Parren and D. R. Burton (2001). "gp120: Biologic aspects of structural features." Annu Rev Immunol 19: 253-274.
4. Pejchal, R., K. J. Doores, L. M. Walker, R. Khayat, P. S. Huang, S. K. Wang, R. L. Stanfield, J. P. Julien, A. Ramos, M. Crispin, R. Depetris, U. Katpally, A. Marozsan, A. Cupo, S. Maloveste, Y. Liu, R. McBride, Y. Ito, R. W. Sanders, C. Ogohara, J. C. Paulson, T. Feizi, C. N. Scanlan, C. H. Wong, J. P. Moore, W. C. Olson, A. B. Ward, P. Poignard, W. R. Schief, D. R. Burton and I. A. Wilson (2011). “A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield.” Science 334(6059): 1097-1103.
5. Julien, J. P., D. Sok, R. Khayat, J. H. Lee, K. J. Doores, L. M. Walker, A. Ramos, D. C. Diwanji, R. Pejchal, A. Cupo, U. Katpally, R. S. Depetris, R. L. Stanfield, R. McBride, A. J. Marozsan, J. C. Paulson, R. W. Sanders, J. P. Moore, D. R. Burton, P. Poignard, A. B. Ward and I. A. Wilson (2013). “Broadly neutralizing antibody PGT121 allosterically modulates CD4 binding via recognition of the HIV-1 gp120 V3 base and multiple surrounding glycans.” PLoS Pathog 9(5): e1003342.

Role of neutralizing antibodies in preventing and treating HIV infection

6. Poignard, P., R. Sabbe, G. R. Picchio, M. Wang, R. J. Gulizia, H. Katinger, P. W. Parren, D. E. Mosier and D. R. Burton (1999). "Neutralizing antibodies have limited effects on the control of established HIV-1 infection in vivo." Immunity 10(4): 431-438.
7. Hessell, A. J., P. Poignard, M. Hunter, L. Hangartner, D. M. Tehrani, W. K. Bleeker, P. W. Parren, P. A. Marx and D. R. Burton (2009). "Effective, low-titer antibody protection against low-dose repeated mucosal SHIV challenge in macaques." Nat Med 15(8): 951-954.
8. Moldt, B., E. G. Rakasz, N. Schultz, P. Y. Chan-Hui, K. Swiderek, K. L. Weisgrau, S. M. Piaskowski, Z. Bergman, D. I. Watkins, P. Poignard and D. R. Burton (2012). "Highly potent HIV-specific antibody neutralization in vitro translates into effective protection against mucosal SHIV challenge in vivo." Proc Natl Acad Sci U S A 109(46): 18921-18925.
9. Poignard, P., B. Moldt, K. Maloveste, N. Campos, W. C. Olson, E. Rakasz, D. I. Watkins and D. R. Burton (2012). "Protection against high-dose highly pathogenic mucosal SIV challenge at very low serum neutralizing titers of the antibody-like molecule CD4-IgG2." PLoS One 7(7): e42209.
10. Barouch, D. H., J. B. Whitney, B. Moldt, F. Klein, T. Y. Oliveira, J. Liu, K. E. Stephenson, H. W. Chang, K. Shekhar, S. Gupta, J. P. Nkolola, M. S. Seaman, K. M. Smith, E. N. Borducchi, C. Cabral, J. Y. Smith, S. Blackmore, S. Sanisetty, J. R. Perry, M. Beck, M. G. Lewis, W. Rinaldi, A. K. Chakraborty, P. Poignard, M. C. Nussenzweig and D. R. Burton (2013). "Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys." Nature 503(7475): 224-228.

HIV broadly neutralizing antibodies

11. Walker, L. M., S. K. Phogat, P. Y. Chan-Hui, D. Wagner, P. Phung, J. L. Goss, T. Wrin, M. D. Simek, S. Fling, J. L. Mitcham, J. K. Lehrman, F. H. Priddy, O. A. Olsen, S. M. Frey, P. W. Hammond, G. P. I. Protocol, S. Kaminsky, T. Zamb, M. Moyle, W. C. Koff, P. Poignard and D. R. Burton (2009). "Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target." Science 326(5950): 285-289.
12. Walker, L. M., M. Huber, K. J. Doores, E. Falkowska, R. Pejchal, J. P. Julien, S. K. Wang, A. Ramos, P. Y. Chan-Hui, M. Moyle, J. L. Mitcham, P. W. Hammond, O. A. Olsen, P. Phung, S. Fling, C. H. Wong, S. Phogat, T. Wrin, M. D. Simek, G. P. I. Protocol, W. C. Koff, I. A. Wilson, D. R. Burton and P. Poignard (2011). "Broad neutralization coverage of HIV by multiple highly potent antibodies." Nature 477(7365): 466-470.
13. Locci, M., C. Havenar-Daughton, E. Landais, J. Wu, M. A. Kroenke, C. L. Arlehamn, L. F. Su, R. Cubas, M. M. Davis, A. Sette, E. K. Haddad, A. V. I. P. C. P. I. International, P. Poignard and S. Crotty (2013). “Human circulating PD-1+CXCR3-CXCR5+ memory Tfh cells are highly functional and correlate with broadly neutralizing HIV antibody responses.” Immunity 39(4): 758-769.
14. Landais E, Huang X, Havenar-Daughton C, Murrell B, Price MA, Wickramasinghe L, Ramos A, Bian CB, Simek M, Allen S, Karita E, Kilembe W, Lakhi S, Inambao M, Kamali A, Sanders EJ, Anzala O, Edward V, Bekker LG, Tang J, Gilmour J, Kosakovsky-Pond SL, Phung P, Wrin T, Crotty S, Godzik A, Poignard P. (2016) “Broadly Neutralizing Antibody Responses in a Large Longitudinal Sub-Saharan HIV Primary Infection” Cohort. PLoS Pathog. Jan 14;12(1):e1005369. doi: 10.1371/journal.ppat.1005369. eCollection 2016 Jan.
15. MacLeod DT, Choi NM, Briney B, Garces F, Ver LS, Landais E, Murrell B, Wrin T, Kilembe W, Liang CH, Ramos A, Bian CB, Wickramasinghe L, Kong L, Eren K, Wu CY, Wong CH; IAVI Protocol C Investigators & The IAVI African HIV Research Network, Kosakovsky Pond SL, Wilson IA, Burton DR, Poignard P. (2016) “Early Antibody Lineage Diversification and Independent Limb Maturation Lead to Broad HIV-1 Neutralization Targeting the Env High-Mannose Patch.” Immunity. May 17;44(5):1215-26. doi: 10.1016/j.immuni.2016.04.016.

Complete list of publications:
http://www.ncbi.nlm.nih.gov/myncbi/browse/collection/43975132/?sort=date&direction=ascending