AGE DA. 8:00-8:30 Breakfast All. 8:30-8:40 Introductions All. 8:40-8:55 Mandate of the Enterprise Alan Bernstein

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1 200 Park Ave. S. Suite 1501 New York, NY Ph: Fax: THE GLOBAL HIV VACCI E E TERPRISE (THE E TERPRISE) I AUGURAL MEETI G OF THE SCIE CE COMMITTEE WED ESDAY, JA UARY 21, 2009, E TERPRISE OFFICES, EW YORK MI UTES AGE DA 8:00-8:30 Breakfast All 8:30-8:40 Introductions All 8:40-8:55 Mandate of the Enterprise Alan Bernstein 8:55-9:00 Role of the Science Committee Rafi Ahmed 9:00-11:00 Scientific Priorities for the Enterprise Scientific Strategic Plan: Current and Future All 11:00-11:15 Break 11:15-11:45 Post STEP: What Have We Learned and Future Directions Larry Corey 11:45-12:00 Breakout Logistics Alan Bernstein 12:00-1:00 Lunch 1:00-2:00 Breakout Discussion: Top Scientific Priorities Three Discussion Groups 2:00-3:30 Consensus Discussion: Top Scientific Priorities All 3:30-3:45 Break 3:45-4:15 Next Steps and Action Items Alan Bernstein 4:15 Adjourn i

2 PARTICIPA TS SCIE CE COMMITTEE MEMBERS: Alan Aderem, Institute for Systems Biology, USA Rafi Ahmed (Chair), Emory University, USA Françoise Barré-Sinoussi, Institut Pasteur, France Dennis Burton, The Scripps Research Institute, USA Larry Corey, University of Washington, USA Barton Haynes, Duke University Medical Center, USA Bette Korber, Los Alamos National Laboratory, USA Andrew McMichael, University of Oxford, UK Gary Nabel, National Institutes of Health, USA Michel Nussenzweig, Rockefeller University, USA Giuseppe Pantaleo, University of Lausanne, Switzerland Louis Picker, Oregon Health & Science University, USA Rino Rappuoli, Novartis Vaccines and Diagnostics, Italy Robin Shattock, St George's University of London, UK Ralph Steinman, Rockefeller University, USA Anna-Lise Williamson, University of Cape Town, South Africa EX-OFFICIO MEMBERS: Catherine Hankins, UNAIDS, Switzerland Margaret (Peggy) Johnston, National Institutes of Health, USA Wayne Koff, International AIDS Vaccine Initiative, USA Yves Lévy, Hôpital Henri Mondor, France Manuel Romaris, European Commission, Belgium Nina Russell, Bill & Melinda Gates Foundation, USA E TERPRISE SECRETARIAT: Alan Bernstein, Executive Director Jennifer Ferré, Assistant to the Executive Director Myra Ozaeta, Director of External Relations Candace Rosen, Senior Adviser on Strategic Planning and Policy Development Brant Silvers, Director of Operations Yegor Voronin, Science Officer OBSERVERS: Emily Bass, AIDS Vaccine Advocacy Coalition, USA Anna Laura Ross, French National Agency for Research on AIDS and Viral Hepatitis, France SC MEMBERS U ABLE TO PARTICIPATE: Arnold Levine, Institute for Advanced Study, USA Pontiano Kaleebu, Uganda Virus Research Institute, Uganda ii

3 EXECUTIVE SUMMARY The inaugural meeting of the Global HIV Vaccine Enterprise (the Enterprise) Science Committee (SC) convened on January 21, 2009, at the Enterprise s office in New York City, with the purpose of identifying critical issues in HIV vaccine research and development that must be addressed in the updated Enterprise Scientific Strategic Plan (SSP). Sixteen of the eighteen SC members and all six ex-officio SC members participated in the meeting. The Enterprise also invited a member of the AIDS Vaccine Advocacy Coalition to observe the SC Meeting. Following a brief introduction to the Enterprise by Dr. Alan Bernstein, Executive Director of the Enterprise, and an overview of the role of the SC by Dr. Rafi Ahmed, Chair of the SC, members were asked to discuss current and future scientific priorities. This initial, free-flowing discussion highlighted the need for increased understanding of immunology and virology in the field of HIV vaccine research and development. Key points from the initial discussion of scientific priorities included: It is essential to learn more about antigen processing, including the effects of the vector and the insert on processing, the mechanisms underlying masking of conserved epitopes, and the nature of epitope immunodominance. Multiple potential effects of the vaccine must be considered and addressed through research (e.g., the vaccine may allow control or prevention of infection). Nonhuman primate (NHP) models are best suited to address basic research questions, including mechanisms of immune protection, not to serve as gatekeepers to human trials. Technological advances are required to study the immune response in humans (e.g., in vivo imaging). In particular, modalities are needed to monitor immune responses in the mucosa, especially the vaginal mucosa. Ex vivo approaches look promising for understanding certain aspects of human immunobiology. Leveraging recent technological advances is critical for the success of HIV vaccine research. Although all neutralizing antibodies observed to date are directed against the envelope trimer, its genetic variability and phenotypic instability are major barriers to the development of an effective HIV vaccine. Many studies have evaluated the levels of antibody required to produce effective sterilizing immunity. Encouragingly, recent data suggest that these levels are somewhat lower than initially hypothesized and are in accordance with those a vaccine might realistically elicit. An increased focus must be placed on antibody functional activities beyond conventional neutralization (e.g., antibody-dependent cell-mediated cytotoxicity, Fc-mediated effects, the impact of isotype, and the role of aggregation and immune complexes). Following the initial group discussion Dr. Larry Corey, Principal Investigator of the HIV Vaccine Trials Network, presented a review of the updated results from the STEP trial highlighting lessons learned and iii

4 factors to consider in future HIV vaccine trials. Next the SC members were divided randomly into three breakout groups that each reviewed the relevancy of the scientific priorities in the existing Enterprise SSP and identified current and future critical scientific issues in HIV vaccine research and development. The full SC then reconvened to discuss the scientific priorities of the three breakout groups in order to come to consensus on the preliminary scientific priorities for the Enterprise to consider including it is updated SSP, which are listed below: 1. Identify, exploit, and measure the cellular and molecular mechanisms underlying the protective immune response. 2. Leverage current and future understanding of the immunologic vulnerabilities of HIV in vaccine design; in particular, study the early events in HIV infection in greater detail. 3. Use NHP models to answer the fundamental questions surrounding transmission, infection, and protection. Implement an iterative process in which NHP model experiments and phase zero and phase I clinical trials interact closely to inform and modify each other. 4. Develop a solid understanding of human immunobiology; especially of T- and B-cell biology, antigen processing and presentation, adjuvants, mucosal immunity, and the role of complement and other Fc-mediated mechanisms. 5. Conduct ongoing vector research, with an emphasis on encouraging comparability and standardization of approaches, in order to keep up with advances in the fundamental understanding of human HIV immunobiology. Finally, Dr. Bernstein described the next steps in the development of the updated Enterprise SSP. The Enterprise Secretariat in conjunction with the SC Chair will define WGs based on the themes discussed during the current meeting and choose co-chairs: one from the Science Committee and the other from within or external to HIV vaccine research and development. Each WG will include 8 to 10 additional Working Group Recommendations Consultations (SC Chair/WG Co-Chairs) Enterprise Council SSP draft Next Steps: Working Group Recommendations Leading Non-HIV Scientists $ Funders Community and Advocacy Groups Industry (?) SSP Published October 2009 AIDS Vaccine 2009 Conference members of the scientific community and will develop a comprehensive set of recommendations that will subsequently be discussed with leading non-hiv scientists, funding bodies, community and advocacy groups, and industry. Following review by the Enterprise Council, the WGs will draft sections of the Enterprise SSP. The Enterprise Secretariat will coordinate and assemble the Enterprise SSP and will publish it in a major, peer-reviewed journal in iv

5 DETAILED SUMMARY OF DISCUSSIO S MA DATE OF THE E TERPRISE Dr. Alan Bernstein, Executive Director, Global HIV Vaccine Enterprise The meeting was opened by Dr. Alan Bernstein, Executive Director of the Global HIV Vaccine Enterprise (the Enterprise), who summarized the mission and vision of the Enterprise, the purpose of the Enterprise Scientific Strategic Plan (SSP), and the goals for the inaugural Enterprise Scientific Committee (SC) meeting. The mission of the Enterprise is to accelerate the research and development of a safe and effective preventive HIV vaccine. This meeting represented an important first step toward updating the Enterprise s SSP, which was drafted in The SSP will be used as a guide for the Enterprise and the HIV vaccine research and development field by highlighting areas of particular or neglected opportunity, delineating major obstacles to vaccine discovery and development, serving as the foundation for an integrated, global effort to inform research efforts towards developing a safe and effective preventive HIV vaccine. Dr. Bernstein emphasized the importance of a collaborative approach that involves scientific and medical researchers, funders, advocates, government agencies, industry, and the broader community of individuals and organizations with an interest in developing an effective vaccine. This plan updates the initial 2005 plan. Given the recent release of the STEP study results, Dr. Bernstein emphasized that it is more critical than ever for the field to innovate and integrate new ideas, new researchers, particularly young and early career investigators from the developed and developing worlds, and new and powerful existing technologies into HIV vaccine research and development. ROLE OF THE SCIE CE COMMITTEE Dr. Rafi Ahmed, Chair, Science Committee Dr. Ahmed, Director of the Emory Vaccine Center and Chair of the Enterprise SC, explained that the SC members included experts in HIV research, scientists with an outside perspective, as well as ex-officio members from six of the seven founding stakeholders of the Enterprise. The primary role of the SC is to identify the scientific issues in the field today and in the foreseeable future, including major obstacles to vaccine development. Citing the tremendous diversity of the virus, Dr. Ahmed noted that any approach to the development of an HIV vaccine will require an in-depth understanding of human immunobiology. Dr. Ahmed summarized some of the failed approaches to the development of an HIV vaccine, including the gp120 vaccine and the gag/pol/nef trivalent vaccine that was tested in the STEP study. These trials, especially the STEP trial, have raised many questions and have highlighted the importance of deepening our understanding of the human response to HIV and HIV immunogens. 1

6 Dr. Ahmed defined two key issues in HIV vaccine development. First, how do we address the tremendous diversity of the virus? Second, how do we broaden immune response? Using these questions as an outline, he asked attendees to participate in an open discussion of future scientific priorities for the Enterprise SSP. SCIE TIFIC PRIORITIES FOR THE E TERPRISE SCIE TIFIC STRATEGIC PLA : CURRE T A D FUTURE All The initial discussion focused on efforts to broaden the T-cell response, including recent research and potential future directions. Following this discussion, attendees briefly addressed the B-cell response to vaccination. Several labs are developing artificial HIV strains based on within-clade consensus sequences; this approach cuts in half the genetic distance between the vaccine strain and circulating strains. The consensus strain can be built to minimize branch lengths ( center of tree approach) or to target an ancestral strain ( root of the tree approach). Both strategies produce similar responses. A number of groups have explored polyvalent approaches with an emphasis on the HIV envelope. One SC member noted that these approaches are insufficient, and that gag and pol must be studied as well. Also under examination are attempts to design artificial mosaic antigens. One SC member s lab has developed an approach that assembles 9-mers most commonly found in nature into something resembling real proteins, which appear to be well expressed. Data on the first published mouse study show that mosaic antigens are much more cross-reactive than three natural strains. Thus far, data on ongoing primate studies currently using this concept suggest that they are immunogenic and well expressed. Results will be available in several months. In preclinical models, mosaic proteins are well expressed and immunogenic. However, less breadth might be observed in humans than in NHP models. An SC member noted that there will be a need for a larger number of phase I trials to test the immunogenicity and breadth of different candidate vaccines. A second SC member is working with gag and nef mosaics versus consensus in a recombinant vaccinia virus vector. Nearing completion, the trial will determine whether NYVAC is sufficiently immunogenic to warrant further tests. All of the described strategies have two main goals: (1) to generate an immune response that deals with HIV sequence diversity with a greater likelihood of interaction at initial infection, and (2) to create an immune response raised to multiple viral variants, making escape less likely and driving the virus into a low fitness area on the fitness landscape. 2

7 In the STEP trial, the CD8 responses to Ad5 were to the conserved regions of Ad5. The CD8 responses to gag, nef, and pol inserts were confined to the variable regions. How to translate this data into human trials and understanding why this happens are important issues. In short, will a synthetic immunogen in which multiple 9-mers are introduced actually be seen and processed so that breadth is achieved? A greater understanding of the mechanics of what goes into antigen processing is required. Key questions include: o What are the mechanisms through which the vector affects processing of the insert? o Is there immune escape or masking of conserved epitopes? If so, what are the mechanisms, and how can these epitopes be unmasked? Polyepitope approaches have not yet been successful. One approach, consisting of 20 gag epitopes linked like beads on a string, did not elicit a robust CD8 response. A second polyepitope approach used a linker strategy and was not at all immunogenic. Based on these results, SC members were inclined to favor immunogens designed to look like natural proteins. One SC member stated that viral escape is the primary concern in vaccine development. In short, the problem is not making epitopes that can elicit a broadly reactive immune response but figuring out which epitopes generate responses that can act against the virus. The most important missing element is an understanding of viral bag of tricks that allow HIV to evade responses of immune system. There was some discussion about the kind of vaccine under consideration: is the vaccine being developed to control or prevent infection? An SC member pointed out that these two approaches may coincide because there is data that shows that if the virus is controlled in the genital mucosa, transmission can be prevented. However, there is a major difference between post-peak control and the much narrower window of opportunity for initial control in the mucosa. Another SC member stated that there is no data to support the idea that breadth of immune responses is beneficial. People who control the virus often exhibit narrow immune responses. Alternatively, it is possible that our understanding of the breadth is not correct. Do broad responses target a single conserved epitope or multiple diverse epitopes? Understanding immunodominance should be a high priority. It will be impossible to design an immunogen around immunodominance without understanding the mechanistic underpinnings of this phenomenon. Indeed, it is not even clear whether immunodominance is beneficial or harmful for protective immune responses. Another SC member summarized three key issues to be addressed in immunogen research agenda: (1) prevention vs control, (2) the number of epitopes vs key epitopes, and (3) immunodominance issues. 3

8 An SC member noted a tension between wanting to understand more about basic immunobiology of the disease and a desire to test various approaches in humans. Is it possible to address key questions - e.g., understanding antigen processing, vector dependence, and epitope masking - without undertaking full-scale human trials? o One SC member suggested an iterative approach in which an NHP model is used to establish a potential vaccine candidate and a subsequent early stage clinical trial is conducted to test it. o A second SC member disagreed with this approach. This SC member believed that NHP models have not been used appropriately. Currently, NHPs are used as a screen for vaccine candidates but should be used to understand basic facts about virus biology and host immunology. There is an urgent need to use NHPs to explore fundamental questions of T-cell biology, breadth, and immunodominance. An SC member outlined three possibilities for design of a vaccine: o Generating sterilizing immunity via antibodies alone. This approach is probably not viable because of the concentrations of antibody needed. o Effectively sterilizing immunity in which the infection would be confined to a local site. Such an approach would be antibody-based but would also involve a CD8 response. o Permitting dissemination of the virus with subsequent control. This SC member believed the second approach is the most realistic; however, another SC member noted that there are few, if any, vaccines that fail to block the initial infection yet provide subsequent control of infection. There is a spectrum of T-cell responses that occur naturally. It is critical to understand which pathways lead to the production of HIV-specific T-cells. NHP models must be used to elucidate these pathways. These results can then be bridged into approaches for human phase I trials. Another SC member emphasized the major difference between controlling and preventing infection. In a control scenario, where a large amount of replicating virus provides for many chances to escape, a hit hard, hit early approach may be more effective. Regardless, it is critical to understand how to get the right T-cells to the right place. To date most T-cell work has concentrated on the upper GI tract; very little work has been done on the rectum and the genital tract. There are likely to be major differences among these sites requiring a very different immunization regime determined by the portal of entry. There was concern about concentrating on a single vector. In parallel to immunologic studies, there is also a need to evaluate different vectors and to have a detailed understanding of how each vaccine vector affects insert immunogenicity in mice, primates, and humans. The chair asked attendees for opinions regarding technical advances needed to enable monitoring response on mucosal surfaces. 4

9 o According to one SC member, rectal T-cells are relatively easy to obtain because numerous biopsies can be taken. Only a limited number of genital T-cells can be obtained without biopsy, and these are generally not viable. Technology needs to be developed to enable meaningful experiments on vaginal mucosa. o Another member pointed out that HIV research is not on the current edge of technology. Methods are available to investigate infection on a single-cell level, assessing its proteome and transcriptome. New sequencing technologies are underutilized. It is currently possible to directly study human immunobiology. The chair noted that if the purpose of a vaccine is to stop disease early, efficacy is dependent upon pre-existing, broadly neutralizing antibodies. According to an SC member, one clear challenge is the lack of immunogens that elicit reasonable levels of broadly neutralizing antibodies in animals. Some hope exists for eliciting broadly neutralizing antibodies. There are some broadly neutralizing antibodies produced by infected patients. However, these antibodies have unusual features and are not elicited frequently. Immunogen design will need to be oriented towards obtaining a similar response. One SC member suggested that the biggest single issue is that all neutralizing antibodies are targeted against the envelope trimer. One reason we do not have a vaccine that elicits decent antibodies is because this trimer is unstable. The difficulty of producing the trimer in a recombinant form represents a major challenge to the field. Many studies have been conducted that evaluate the levels of antibody needed to provide an effective response to initial infection. It has long been hypothesized that these levels must be very high. However, recent data suggest that the levels required are somewhat lower than initially hypothesized and in the realm of what a vaccine might produce. Broadly neutralizing antibodies can be placed into several categories: the membrane proximal region of the gp120 trimer, the stalk of the gp120 trimer, the CD4 binding site, and the sugars on the gp120 trimer. POST-STEP: WHAT HAVE WE LEAR ED A D FUTURE DIRECTIO S Dr. Larry Corey Dr. Corey, Principal Investigator of the HIV Vaccine Trials Network (HVTN) and co-director of the Vaccine and Infectious Diseases Institute, both at Fred Hutchinson Cancer Research Center in Seattle, WA, provided an overview of the updated findings and implications of the STEP trial. 5

10 Brief Summary A detailed, longitudinal look at post-acquisition data from STEP suggests that the vaccine had no effect on viral load, CD4 T-cell count, or time to initiation of antiretroviral therapy (e.g., the vaccine neither improved nor caused an increased rate of disease progression in the overall patient population or in any subgroup). The vaccine was immunogenic overall, but in some respects it could be considered poorly immunogenic. The overall frequency of T-cell response was high; however, only 31% of the vaccinated population mounted both a CD4 and CD8 T-cell response. Data from STEP also indicate that HSV-2 infection increases the risk of HIV acquisition approximately threefold with effects seen in both vaccine and placebo recipients. The effect of HSV-2 on HIV acquisition is greater than the effect of past Ad 5 infection. Analyses of STEP data continue to show that prior exposure to Ad 5 infection confers an increased risk for acquisition, although the effect of Ad 5 seropositivity on acquisition appears to be diminishing with more events. The minimal effect of Ad 5 immunity on HIV acquisition was further confirmed by Corey and colleagues in a study using data from Multicenter AIDS Cohort Study and HIV Prevention Trial Network. It is noteworthy, however, that while Ad 5 seropositivity does not change the magnitude of response, it significantly changes the breadth of response. Data from analyses of STEP, to be presented at the 16 th Conference on Retroviruses and Opportunistic Infections, also suggest that there is a relationship between HLA type and viral load. Key outcomes from the STEP trial include: In selected individuals, vaccination produces an immune response that can be associated with an in vivo effect on viral load. These immune responses are on an epitope-specific basis, and at present, most appear to lie within the gag protein of HIV-1. These data suggest the need to concentrate efforts on the HIV vaccine inserts in a vaccine regimen. In summary, the STEP trial has contributed significantly to the scientific understanding of vaccine design. First, the trial demonstrated that the concept of a simple vaccine consisting of homologous vector and homologous insert is unlikely to be effective. Second, the trial showed that vector-induced immunity needs to be evaluated in vaccine development, including tissue-specific responses. Third, the study showed that associations between vaccine-induced responses and viral load can be defined within the context of a clinical trial. Finally, the trial illustrated the urgent need to understand the biology of immunodominance following vaccination and the impact that this can have on effectiveness especially because of the genetic diversity of HIV-1. BREAKOUT DISCUSSIO : TOP SCIE TIFIC PRIORITIES Following a review of updated results from the STEP trial, SC members were divided at random into three groups in which they reviewed the scientific priorities in the current Enterprise SSP for relevancy 6

11 and identified and discussed top scientific priorities for the future of HIV vaccine research. Below are each group s s key scientific priorities: Group 1 1. Decipher the mechanisms by which vaccines confer protection rather than research the events associated with progression of disease. 2. Increase the focus on fundamental immunology, particularly as it relates to antigen processing, immunogenicity, and avidity of response. 3. Develop state-of-the art technology to evaluate T- and B-cell function at the site of viral entry. 4. Create smarter adjuvants that are most appropriate for inducing localization of T-cells to gut mucosa. Establish broad-based access to these reagents by researchers. 5. Increase research into appropriate vectors including studies in which (a) the insert is kept constant to allow side-by-side comparisons of vectors and (b) the vector remains constant in order to compare inserts. Allow cross-validation of multiple studies by providing open access to data and utilize systems biology to compare different strategies. 6. Increase understanding of (a) the mechanisms through which broadly neutralizing antibodies act on HIV and (b) antibody function beyond neutralization (e.g., complement activation, antibody-dependent cellular cytotoxicity and other Fc functions). Group 2 1. Instead of a pipeline approach to research (defined by the group as testing vectors with little rational basis ), conduct vector design firmly grounded in an understanding of immunobiology. 2. Examine the nature of protective T-cell and antibody responses and the circumstances under which this protection can be elicited. 3. Broaden understanding of the lentiviral lifecycle, including an evaluation of consequences of viral infection on different subsets of T-cells. 4. Increase the emphasis on using NHP models as basic research tools rather than their current use as gatekeepers to human trials. 5. Use mouse models to examine basic issues in immunology. (In general, the group was less enthusiastic about the ability of mouse models to answer critical questions in HIV immunobiology and vaccine research.) 6. Invest in new technologies, including genomic and transcriptional analysis, micro RNA, and proteomic responses to infection. 7. Gain a more detailed understanding of gp120 structure and function. 7

12 Group 3 Early events in infection 1. Examine immunopathogenesis, acquisition prevention, and immunodominance in the context of various portals of entry. 2. Determine the feasibility of preventing acquisition with a T-cell vaccine. 3. Identify the determinants of viral activation from latency using NHP models. 4. Further evaluate the events in early infection (defined by the group as the first 96 hours after infection). In particular, this group emphasized the importance of examining the early T-cell response to infection. Animal models 1. Develop a systematic approach to modeling HIV acquisition. 2. Apply an acquisition model to a variety of challenge viruses. 3. Evaluate current viral vaccines in order to learn how they should be extrapolated in the HIV arena. CO SE SUS DISCUSSIO : TOP SCIE TIFIC PRIORITIES Next, using the scientific priorities identified in the three breakout groups as a starting point, the SC identified preliminary scientific priorities for the updated Enterprise SSP. The SC was informed that the preliminary scientific priorities would be further refined by the Chair and Enterprise secretariat with the ultimate goal of defining 6 to 8 working groups (WGs) that will provide content for the updated Enterprise SSP. Below is a summary of the synthesized outcomes of this discussion. Preliminary Scientific Priorities Overarching principle: Move away from an empirical approach to vaccine development toward one based on a fundamental immunologic understanding of the host-virus relationship. 1. Identify, exploit, and measure the cellular and molecular mechanisms underlying the protective immune response. 2. Leverage current and future understanding of the immunologic vulnerabilities of HIV in vaccine design; in particular, study the early events in HIV infection in greater detail. 3. Use NHP models to answer the fundamental questions surrounding transmission, infection, and protection. Implement an iterative process in which NHP model experiments and phase zero and phase I clinical trials interact closely to inform and modify each other. 8

13 4. Develop a solid understanding of human immunobiology; especially of T- and B-cell biology, antigen processing and presentation, adjuvants, mucosal immunity, and the role of complement and other Fc-mediated mechanisms. 5. Conduct ongoing vector research, with an emphasis on encouraging comparability and standardization of approaches, in order to keep up with advances in the fundamental understanding of human HIV immunobiology. NEXT STEPS Dr. Bernstein described the next steps in the development of the updated Enterprise SSP (see slides below). The Enterprise Secretariat in conjunction with the SC Chair will define WGs based on the themes discussed during the current meeting and choose co-chairs: one from the Science Committee and the other from within or external to HIV vaccine research and development. Each WG will include 8 to 10 additional members of the scientific community and will develop a comprehensive set of recommendations that will subsequently be discussed with leading non-hiv scientists, funding bodies, community and advocacy groups, and industry. Following review by the Enterprise Council, the WGs will draft sections of the Enterprise SSP. The Enterprise Secretariat will coordinate and assemble the Enterprise SSP and will publish it in a major, peer-reviewed journal in Next Steps: Working Group Recommendations Working Group Recommendations Leading Non-HIV Scientists Consultations (SC Chair/WG Co-Chairs) $ Funders Community and Advocacy Groups Industry (?) Enterprise Council SSP draft SSP Published October 2009 AIDS Vaccine 2009 Conference 9

14 Next Steps: SSP Science Committee (SC) THEMATIC WORKING GROUP: Co-Chairs SC member + External Scientific Priorities End of February: Thematic Working Groups 6-8 members global & industry representation input on members from SC Chair & Enterprise Early April: Specific Recommendations Measureable Milestones to Track Progress Science writer Next Steps: Scientific Strategic Plan (SSP) Science Committee Priority Scientific Areas Enabling Themes e.g., Young and Early Career Investigators Systems biology Translational continuum NHP/humans Data-sharing culture others 10

15 Next Steps: YECI Young and Early Career Investigators (YECI) Purpose: 1. Articulate importance of young investigators as drivers of innovation 2. Propose structural changes required to engage and retain new scientific talent Timeline: January 27 Inaugural meeting by teleconference Mid-February Second meeting by teleconference Mid-March Face-to-face meeting in NY Spring 2009: IntegrateYECI section into SSP Next Steps: CRIP Sections CRIP Sections: Parallel process to Scientific Priorities An Expert Committee will: 1. Review 2005 SSP CRIP sections: Clinical trials capacity Regulatory capacity Intellectual property Product development and manufacturing 2. Determine key topics for 2009 SSP CRIP 11

16 Next Steps: CRIP sections 3. Similar process to Science Committee -Thematic working groups -Recommendations -Consultations Funders HIV vaccine scientists Community and Advocates Industry $ Enterprise Council CRIP sections draft Integrate CRIP sections into SSP 12