HIV Vaccine Conference

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HIV Vaccine Conference The B cell response to HIV and HIV vaccines: From broadly neutralizing to non-neutralizing antibodies In memory of Dr. Charles Mérieux Organized by Fondation Mérieux Les Pensières Fondation Mérieux Conference Center Veyrier du Lac - November 5 to 7, 2012 1

Scientific Committee Members Brigitte Autran Françoise Barré-Sinoussi Jean-François Delfraissy Wayne Koff Yves Levy Gary Nabel Nina Russell Frederic Tangy Britta Wahren Institutions Pitié-Salpêtrière University Hospital, University Pierre and Marie Curie Pasteur Institute ANRS (Agence National de Recherche sur le Sida) Inserm Aviesan IAVI (International AIDS Vaccine Initiative) USA University Paris Est Vaccine Research Institute VRC (Vaccine Research Center) NIH (National Institutes of Health) USA Bill & Melinda Gates Foundation USA Pasteur Institute Karolinska Institute Sweden Steering Committee Members Marc P Girard Christophe Longuet Valentina Picot Institutions French National Academy of Medicine Fondation Mérieux Fondation Mérieux 2

Background Named after the One hundred guards of Emperess Eugenia from (1852-1870), the Cent Gardes symposium was initiated in 1986 by Fondation Mérieux, the Pasteur Institute and Pasteur-Vaccins (which eventually fused with Institut Mérieux to become Pasteur Mérieux Serums and Vaccines, today Sanofi-Pasteur), with the drive and support of Dr Charles Mérieux. It is one of the very first international scientific conferences focusing on HIV/AIDS Vaccine research. First an annual then a bi-annual event, the meeting was initially held at the Marnes-la- Coquette near Paris, in the historical place where the 100 Guards were housed, after the event was moved to Annecy in 2002. After a few years of interruption, the meeting is back to life today at Les Pensières Conference Center, and we hope it will continue unabated in the years to come. The search for a safe and effective HIV vaccine began in the mid-1980, indeed a long journey with several ups and downs. In spite of more than a quarter of a century of hard work, successive attempts for developing a vaccine either have failed or provided only a modest short-lived protection. The quest for an HIV vaccine remains at this time a daunting challenge, but the identification of neutralization epitopes shared by most strains of virus and recognized by broadly neutralizing antibodies (bnabs) has given hope that one might eventually develop a valid protective immunogen. At the same time, there is increasing evidence that non-neutralizing antibodies (n-nabs) may play a pivotal role in vaccine-induced protection, a very different avenue that is worth investigating further. For these reasons, the 2012 conference will be devoted to the study of the B cell response to HIV infection and vaccines: from bnabs to n-nabs. We wish the meeting to be an opportunity for participants to share new findings, to open new collaborations, to generate new thinking and to identify novel promising areas for future research. 3

Objectives -To provide the state of the art on the B cell response to HIV infection, the role of antibodies in protection against HIV infection and the development of an effective B cell response through vaccination. -To describe current challenges and highlight new perspectives for the development of an effective HIV vaccine. -To allow high level exchange within the scientific community, foster comparisons between various vaccine models and strategies, create collaborative approaches and help them move forward. 4

November 5, 2012 13:20-14:00 Registration Alain Mérieux 14:00-14:30 Welcome Addresses Jean-François Delfraissy Stanley Plotkin 14:30-14:35 In memory of Norman Letvin Brigitte Autran 14:35-14:45 Meeting Introduction Marc Girard SESSION I B cell responses to HIV: An overview Chair by: Marie-Paule Kieny & Jean François Delfraissy 14:45-15:35 Broadly neutralizing antibodies to HIV: an overview Dennis Burton 15:35-16:20 Maturation Pathways of HIV Non-Neutralizing Versus Broad Neutralizing Antibodies: Blueprints for Vaccine Design Barton Haynes 16:20-16:50 Coffee Break 16:50-17:35 Dissecting the human B cell response to pathogens Antonio Lanzavecchia SESSION II 17:40-18:00 Biology of the B cell Chair by: Jim Bradac & Stanley Plotkin Dynamic imaging of lymphocyte activation - from single molecule to living tissue Facundo Batista 18:00-18:20 Fc effector functions Jeffrey Ravetch 18:20-18:40 Driving factors and consequences of B cell dysfunctions during HIV-1 infection sca Chiodi 18:40-19:00 Panel Discussion 19:00 Welcome Dinner 5

November 6, 2012 SESSION III The B cell system Chair by: Gabriella Scarlatti & Julie Overbaugh 08:45-09:05 Autoreactive B cells in HIV infection and control Ignacio Sanz 09:05-09:25 09:25-09:45 Complexity of human antibody repertoires, as revealed by high throughput sequence analysis Extensive Somatic Hypermutation in Broadly Neutralizing HIV- 1 Antibodies: the Cart or the Horse? James Crowe Garnett Kelsoe 09:45-10:05 Innate pathway for Human Ab production Michel C. Nussenzweig 10:05-10:25 Panel Discussion 10:25-10:55 Coffee Break SESSION IV 10:55-11:15 Broadly neutralizing Antibodies Chair by: Frederic Tangy & Bonnie Mathieson Neutralizing Antibody Responses in Human Clinical Trials of Candidate HIV-1 Vaccines David Montefiori 11:15-11:35 HIV vaccine design to induce broadly-neutralizing antibodies William Schief 11:35-11:55 Deep Sequencing and the Evolution of the HIV-1 Neutralizing Antibody Response John Mascola 11:55-12:15 Panel Discussion 12:15-14:00 Lunch SESSION V HIV-1 broadly neutralizing antibodies epitopes Chair by: Marie Pancera & Quentin Sattentau 14:00-14:20 HIV- 1 broadly neutralizing epitopes: The CD4-binding site Peter Kwong 14:20-14:40 Development of broadly neutralizing antibody specificities Pascal Poignard 14:40-15:10 Broadly Neutralizing Antibodies to the HIV-1 Glycan Shield Ian Wilson 15:10-15:30 MPER-directed Antibodies from Patients with Broad and Potent Neutralizing Sera Mark Connors 15:30-15:50 Panel Discussion 15:50-16:30 Coffee Break 6

SESSION VI Induction of a broadly neutralizing antibodies response 16:30-16:50 Chair by: Nina Russell & Geppi Pantaleo Broadly Neutralizing Abs for HIV: Immunogen Design and Passive Transfer Gary Nabel 16:50-17:10 Llamas, vaccines and microbicides Robin Weiss 17:10-17:30 Immunoprophylaxis By Gene Transfer: Shortcut To An HIV Vaccine Philip Johnson 17:30-17:50 AAV-8-Mediated Delivery of Broadly Neutralizing Antibodies David Baltimore 17:50-18:10 Panel Discussion SESSION VII Round Table Discussion: The future of clinical efficacy trials Moderator: Gary Nabel 18:10-19:20 Participants: Nina Russell Harriet Robinson Geppi Pantaleo Britta Wahren 19:30 Dinner November 7, 2012 SESSION VIII 08:30-08:50 08:50-09:10 09:10-09:30 Nonneutralizing Antibodies Chair by: Britta Wahren & Francis Barin V2-dependent binding and neutralizing antibodies in HIV-1 subtype C infection Induction of HIV-1 Specific Mucosal Antibodies: AHI and Vaccination In depth characterization of in vitro Ab inhibitory activities and correlates with in vivo protection Lynn Morris Georgia Tomaras Christiane Moog 09:30-09:50 Fc Receptors and Lentivirus Infection Don Forthal 09:50-10:10 Panel Discussion 10:10-10:50 Coffee Break 7

SESSION IX Mucosal Immunity Chair by: Mario Clerici & Julie McElrath 10:50-11:10 Mucosal Barriers to HIV in the Female and Male Genital Tract Minh Dinh 11:10-11:30 11:30-11:50 Mucosal antibodies targeting gp41 for blocking mucosal entry of HIV-1 Virosome-gp41 induces mucosal antibodies that may act as front line defense against HIV-1 entry Morgane Bomsel Sylvain Fleury 11:50-12:10 Moving beyond the RV144 Thai Phase III trial Barton Haynes 12:10-12:30 Panel Discussion 12:30-14:00 Lunch SESSION X 14:00-14:20 14:20-14:40 Animal models Chair by: Shiu Luk Hu & Roger Le Grand Broadly neutralizing Abs generated by SHIV infection in macaques Elicitation of potent systemic and mucosal immune responses against HIV using self-amplifying RNA vaccines Malcom Martin Susan Barnett 14:40-15:00 Novel HIV Vaccine Strategies Dan Barouch 15:00-15:20 The SIVmac251 macaque model recapitulates the protection observed in RV144: immune correlates of protection Veffa Franchini 15:20-15:30 Passive Immunization with IgA Ruth Ruprecht 15:30-15:40 Panel Discussion 15:40-16:30 Coffee Break SESSION XI Conclusions Chair by: Jose Esparza & Patrice Debré 16:30-16:50 Meeting Review Françoise Barré Sinoussi 16:50-17:00 Concluding Remarks Marc Girard End of the Meeting 8

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