Meetings

The Canadian HIV Vaccine Initiative (CHVI) Team Grant in HIV Vaccine Research Partnership Development Forum

AIDS Vaccine 2008 October 2008 Cape Town, South Africa

Executive Summary

The HIV/AIDS epidemic spans the globe and continues to impact the lives of millions of people. It remains clear that the best way to get ahead of this sweeping infection is through the development and global distribution of a preventative vaccine. The recent and well publicized failures of HIV vaccine trials, though disheartening, have left the research community with a strengthened resolve to work towards this goal - each failure offering valuable insight into the final success. There is no doubt that intensifying efforts will lead to a positive outcome.

In support of international HIV vaccine discovery, the Government of Canada launched the Canadian HIV Vaccine Initiative (CHVI), a partnership between five federal departments and the Bill & Melinda Gates Foundation. This joint initiative recognizes the need for specific attention in all areas of HIV vaccine research from basic discovery to issues of ethics and social acceptance; and through the Discovery and Social Research component is launching key funding opportunities to address them. The Canadian Institutes of Health Research (CIHR) and the Canadian International Development Agency (CIDA) are working together to support HIV vaccine discovery and social research while strengthening capacity and promoting greater involvement and collaboration amongst researchers in Canada and low- and middle-income countries (LMIC).

During a consultation session in February 2008, feedback from the HIV community in offered insight into the funding opportunities which would yield the greatest success. With the advice offered, Operating and Catalyst Grant competitions were launched in the summer of 2008. Moving forward, the focus has shifted to supporting teams of Canadian and developing country researchers with interest in research and research capacity related to the discovery of HIV vaccines and related research, such as mucosal and innate immunity, as well as social, behavioural and ethical issues including cultural and other sensitivities to HIV vaccines use and their impact on behaviour. A Team Grant Request for Applications (RFA) is expected to be launched early in 2009.

To ensure that this funding opportunity is relevant and most responsive to the needs of the HIV community, CHVI held a Partnership Development Workshop in October 2008. Held in Cape Town as a satellite session of the AIDS Vaccine 2008 Conference, the session capitalized on the gathering of international researchers to garner feedback on the draft CHVI Team Grant RFA. Over the course of the half-day workshop, participants from seven different countries heard from key players in the HIV vaccine movement, were introduced to the CHVI Team Grant funding opportunity in detail and provided input on its design. The session made it clear that a team approach to vaccine research was indeed required but that improvements were needed to increase the impact of the funding opportunity. In addition to valuable insight on administration of the RFA, the following two broad topic areas were identified as requiring additional thought:

• Encouraging new and young researchers – given the current trend of thought that "New Minds, New Ideas" represent the most promising path forward in this field, does this RFA provide sufficient support to encourage new researchers into the field and to maintain existing ones?; and
• Supporting new ideas and approaches – ensuring that the objectives of the RFA include opportunities for the development of new ideas by allowing new partnerships to emerge.

The CHVI partners are now in discussion to incorporate these elements and build on the recommendations stemming from the workshop into a final funding opportunity which will be released in early 2009. It is anticipated from the response and participation in the satellite session that quality applications from both social and basic researchers will be submitted to this competition once under way.

Top of Page

Introduction

Around the world there are approximately 4.1 million new HIV infections per year and some countries have prevalence rates as high as 25%. Research is needed in many areas of HIV/AIDS but research focused on HIV prevention is seen as a critical step in controlling the epidemic. The world needs preventative and therapeutic HIV vaccines that are safe, effective and globally accessible.

HIV/AIDS threatens the lives of many and compounds stigma and discrimination against people who are already marginalized. There are fears that without a viable vaccine, the spread of HIV could continue unabated, potentially disabling entire countries and regions, wiping out gains in socio-economic development particularly in low- and middle-income countries (LMIC). Therefore, in the absence of a cure, HIV vaccine research and development is a pressing priority.

Background

Canadians understand that what happens globally matters locally and that Canadian research can have a global impact on preventing the spread of HIV and improving the health and quality of life of people living with HIV/AIDS. In 2007, the Canadian HIV Vaccine Initiative (CHVI) was created. This five-year collaborative initiative between the Government of Canada and the Bill & Melinda Gates Foundation represents a significant Canadian contribution to global efforts to develop a safe, effective, affordable and globally accessible HIV vaccine. Industry Canada, the Canadian Institutes of Health Research (CIHR), the Canadian International Development Agency (CIDA), the Public Health Agency of Canada (PHAC) and Health Canada are the representative federal departments involved in this initiative. Together, CIHR and CIDA are responsible for implementing the Discovery and Social Research component of the CHVI that will support HIV vaccine discovery and social research and capacity building initiatives. In keeping with the overarching CHVI principle of global access, true partnership and collaboration amongst researchers in Canada and LMIC will be crucial for the success of these initiatives.

CIHR and CIDA are preparing to launch a Request for Applications (RFA) entitled the "CHVI Team Grants in HIV Vaccine Research" for which funding in the amount of $ 17 million dollars (CDN) will be available. Collaborative teams of Canadian and LMIC researchers will be funded through the CIHR Team Grant program which aims to strengthen health research by supporting teams of talented and experienced researchers conducting high-quality research and providing superior research training and mentorship. The program's emphasis is on the production of new knowledge, and the translation of research findings into improvements in health and the health care system.

Proposals that represent active and meaningful partnerships between community organizations and research teams based in institutions (including universities, colleges, hospitals, and affiliated research institutions) are encouraged. The unifying element underlying all successful CHVI Teams will be a commitment to excellence and the pursuit of a problem-based, collaborative approach to health research.

Top of Page

Goals and Objectives of Session

Recognizing the need to develop a coordinated and focused research effort, CHVI and its partners provided a forum for researchers to meet, share experiences and prepare for this major funding opportunity. The AIDS Vaccine 2008 conference offered a unique opportunity for members of the scientific community to begin to formulate and strengthen research partnerships. Accordingly, a satellite session was held to bring together researchers from the various HIV research domains. The session was open to researchers from all disciplines and countries.

A key eligibility requirement of the CHVI Team Grant is the need for teams to include at least one LMIC institution and at least one Canadian institution and each funded team must involve two co-principal applicants (one from an LMIC and one from a Canadian institution) who will be directors for the program of work and share administrative responsibility for the grant. An overarching goal of this workshop was to foster these partnerships. Interested Canadian and LMIC researchers were afforded an opportunity to meet each other and to discuss areas of common interest with a view to preparing applications for these grants. In addition to providing all participants with an opportunity to meet and network in a stimulating environment, the goals of this Partnership Development Forum were:

• to increase knowledge and understanding of the Canadian HIV Vaccine Initiative and the funding opportunities it offers for Canadian and International researchers;
• to support the researchers by providing an opportunity for them to learn more about the upcoming Large Team Grant funding opportunity;
• enhance collaboration and linkages between Canadian and LMIC researchers and potential partners;
• generate opportunities for future collaboration on innovative research to reduce the global burden of HIV infection; and
• share information and solicit feedback on current research partnerships, identifying challenges and barriers to success.

It was also expected that teams of researchers would take advantage of this opportunity and begin to formulate their proposals to the "CHVI Team Grants in HIV Vaccine Research" Request for Applications to be launched in early 2009.

Top of Page

Speakers and Discussions

Setting the Stage - Presentations in HIV Vaccine Research

The Canadian HIV Vaccine Initiative

Steven Sternthal, Public Health Agency of Canada, Ottawa, Canada

Steven Sternthal is the Acting Director of the Public Health Agency of Canada's Office of HIV Vaccines in Ottawa. The Office of HIV Vaccines is responsible for providing secretariat support for the multi-department/agency Canadian HIV Vaccine Initiative. Steven's work in HIV/AIDS spans over a decade with PHAC and Correctional Service Canada.

Steven Sternthal welcomed researchers and representatives from different countries and institutions and acknowledged their recognition that no one sector can solve this problem alone, and only through innovative partnerships can solutions be found. One novel partnership announced in February 2007 by Prime Minister Stephen Harper and Bill Gates is the CHVI through which Canada is doing its part to contribute to the global cause. This initiative is supported through a five-year investment of $111 million from the Government of Canada and $28 million in funding from the Bill & Melinda Gates Foundation. Within the Government of Canada, the CHVI involves several federal departments and agencies already engaged in HIV/AIDS and vaccine-related issues, including the Canadian International Development Agency, the Public Health Agency of Canada, Industry Canada, the Canadian Institutes of Health Research, and Health Canada. Partnerships and engagement are key priorities for the CHVI and mechanisms that help determine the path forward in establishing these partnerships and sharing information across the different program areas of the CHVI and across sectors are being developed.

The CHVI has 4 funding programs which are in different stages of development -- some are in progress while others are in the consultation or development stage. These include Operating grants related to vaccine discovery, a Pilot Scale HIV Vaccine Manufacturing Facility, a Community Initiatives Fund, Catalyst grants and the focus of this satellite session - Team Grants in HIV Vaccine Research. The Canadian Institutes of Health Research and the Canadian International Development Agency are responsible for implementing this component of the CHVI which will support HIV vaccine discovery and social research capacity building initiatives.

An HIV Vaccine: Where Do We Go From Here

Dr. Alan Bernstein. Executive Director, Global HIV Vaccine Enterprise, New York, United States.

Dr. Bernstein is the inaugural Executive Director of the Global HIV Vaccine Enterprise, an international alliance of researchers, funders and advocates committed to accelerating the development of an HIV vaccine. He is an internationally renowned researcher and the founding President of the Canadian Institutes of Health Research, which he built into one of the world's leading research agencies. Alan has received a number of national and international awards for his research, and has served on a large number of international scientific bodies, including the Science Board of the Grand Challenges for Global Health Initiative.

Dr. Bernstein provided an overview of the field at the moment and where it needs to go and offered an overview of the role the Global HIV Vaccine Enterprise plays in this forum.

Looking across the HIV Vaccine landscape, it is clear that profound challenges remain. From basic science issues of extensive sequence diversity to understanding the immune correlates of protection to more practical issues of limitations with animal models, limited industry engagement and political, ethical and regulatory challenges, there is much still to overcome. Failures should be treated as steps towards accomplishments and the scientific progress within each setback not overlooked or understated. Science is about a diversity of approaches and it will be important that no single scientific approach, no individual team and no one country be depended upon to solve this global problem. Areas for intensified efforts include greater understanding for the basis for long-term non-progression, better exploitation of non-human primate models as well as bringing new technologies such as systems biology, transcriptional profiling, computational biology and RNAi technologies to the forefront.

Young researchers bring energy, creativity, and new approaches to the field and we must endeavour to identify mechanisms to attract and support them in this field to ensure a sustained community of excellent investigators. In addition, investigators from countries most affected by HIV offer new insights and perspectives and should be encouraged by the provision of specific initiatives.

The Global HIV Vaccine Enterprise (GHVE) is a global partnership created by the world's leading funders of HIV/AIDS research to articulate the fastest way forward to a safe and effective preventive HIV vaccine. It creates a global community of problem solvers consisting of funders, scientists, governments, industry, and civil society, working together to devise and implement a global strategic plan to develop a safe and effective preventive HIV vaccine. The GHVE represents the HIV vaccine community by:

• developing and maintaining the Global Strategic Plan;
• serving as a neutral convener, catalyst, and honest broker;
• Mobilizing support for increased resources; and,
• Promoting greater collaboration and coordination

As it moves forward the GHVE will focus on the renewal of the Global Strategic Plan, a Young Investigators Initiative, Systems Biology Initiative and a Preclinical/Clinical Research Initiative

Building HIV Prevention Research Collaborations in Africa: Experience of the Canada-Africa Prevention Trials (CAPT) Network

Dr. David Moore, Research Scientist, BC Centre for Excellence in HIV/AIDS, British Columbia, Canada

Dr. Moore is a Research Scientist with the British Columbia Centre for Excellence in HIV/AIDS and an Assistant Professor in the Faculty of Medicine, Division of AIDS at the University of British Columbia in Vancouver, Canada. From July 2005 until December 2007, he worked with the US Centers for Disease Control as the Project Director and a Co-PI of the Home Based AIDS Care (HBAC) Project in Tororo, Uganda, a randomized clinical trial of different monitoring strategies for HIV-infected adults receiving antiretroviral therapy. Dr. Moore is a Co-applicant of the Canada-Africa HIV Prevention Trials (CAPT) Network and has received a New Investigator Award from the Canadian Institutes for Health Research for a CAPT Network study examining the effectiveness of antiretroviral therapy as an HIV prevention tool in sero-discordant couples.

The Canada Africa Prevention Trials (CAPT) Network was developed in 2006 with a two-year grant from the Global Health Research Initiative. Based on existing collaborations between Canadian HIV researchers and clinicians and African colleagues, the network involves five Canadian sites and eight sites in three African countries. The objectives of CAPT which reach across the two main themes of immune monitoring and prevention research capacity are:

• building a framework for a sustainable network;
• enhancing site capacity by providing staff, resources and training;
• generating research; and,
• developing collaboration with other networks.

In the nearly two years of operation, the network has established the required operational framework, established site capacity and training, begun generating research capacity and knowledge and facilitated collaborations with other networks.

Working internationally on complex problems presents special challenges that teams planning applications to the CHVI Team Grant program must consider. In the CAPT Network as with other international collaborations, the pool of HIV researchers is much smaller than in North America and those who are identified have limited time for individual projects, proposal writing or providing feedback on proposals. There is a need to train more junior researchers (i.e. Master's or PhD training rather than fellowships) and once trained, consideration to support of salaried positions for researchers is necessary. Finding investigators willing and able to commit large amounts of time to African projects can be difficult without additional barriers. All countries have unique strengths and weaknesses making it impossible to apply a "one size fits all" approach to planning and implementation. There is also considerable competition for African sites with other collaborators.

Funding is a major issue with grant duration often being too short to allow real establishment of the project before it begins winding down. There is a need for continuous funding for sites beyond individual trials which would allow infrastructure investment to sustain longer term programs. Few Canadian funders have designed programs which allow funding for international projects leaving foreign NGOs ineligible to receive funding or qualify as Principal Applicants on grants. In addition, management of funds over several years is not possible with short-term funding of activities through deficit accounts and carry-over funding often not allowed.

Building prevention research capacity is critical part of building vaccine research capacity and working as a network can greatly strengthen sites both locally by developing human and HR, physical and administrative infrastructure and globally by transforming locally relevant ideas into high quality research. Addressing the challenges presented will require sustainable long-term funding which CHVI's "Discovery and Social Research Initiative" is an important step to recognizing.

Overview of Team Grant RFA

Dr. Michael Grant, Division of Basic Medical Sciences, Memorial University, Newfoundland, Canada.

Dr. Michael Grant is a full professor of Immunology in the Division of Basic Medical Sciences at the Faculty of Medicine at Memorial University in Newfoundland. Throughout his career, he has studied the immunology of chronic viral infections, especially HIV infection. He has earned personnel awards and research operating funds throughout his career and is a member of the CIHR Institute of Infection and Immunity Advisory Board and Chair of the CIHR HIV/AIDS Research Advisory Committee (CHARAC).

In preparation for the luncheon discussion and afternoon feedback session, Dr. Grant provided a detailed overview of the current version of the CHVI Team Grant RFA. The Team Grant program objectives are to create internationally recognized teams of Canadian and LMIC researchers and support their efforts to contribute important knowledge to the global search for HIV vaccines; build capacity (human and infrastructure) for HIV Vaccines discovery and related social research in Canada and in LMICs; create mechanisms for teams funded under the initiative to network and share information with one another and other relevant international networks and consortia; and, to create mechanisms for ongoing learning and sharing within, between and among funded teams including data sharing, shared platforms and global intellectual property access mechanisms.

It is expected that five to seven large teams will be awarded up to $600K (CAD) per year for periods of up to five years. To ensure the full range of topics are explored, at least one social science team or blended team (basic and social scientists) team and at least one biomedical/basic science team will be funded. The application process will be comprised of both Letter of Intent (LOI) and Full Application phases with teams invited to submit the full applications being eligible for $25K development grants. Teams must originate from at least one LMIC institution and at least one Canadian institution with two co-principal applicants (one from an LMIC and one from a Canadian institution) who will serve as directors of program. Teams may include both basic and social scientists working together or teams composed entirely of social or basic scientists.

This program is intended to support new or established teams with interest and expertise in HIV vaccine research however, "new" teams must demonstrate that they have already developed at least an informal relationship with the intent to work together in the future. In addition to these eligibility criteria, proposals must provide training opportunities for students and young investigators in both Canada and LMICs.

Based on feedback received at a stakeholder consultation held in February 2008, the following priority areas for research were suggested. In the area of Social Research:

• development and evaluation of targeted communication strategies to ensure the participation of at risk groups in the design and implementation of vaccine trials;
• monitoring the attitudes and behaviour of trial participants to assess the impact of trials on risk behaviour in communities affected by HIV;
• investigation of social issues surrounding HIV vaccines including knowledge, acceptability and access;
• ethical issues related to studying vulnerable populations (e.g. adolescents, injection drug users, sex workers);
• patent law and intellectual property issues related to HIV vaccines and related research; and,
• knowledge translation and risk communication relating to HIV Vaccine research.

In the area of Discovery Research:

• novel approaches to induction and long-term maintenance of mucosal innate and adaptive immune responses;
• novel approaches to developing prophylactic vaccines aimed at induction of broadly neutralizing antibodies and B cell responses to HIV
• development and testing of therapeutic HIV vaccines;
• studies aimed at better understanding the correlates of immune protection relating to HIV; and,
• development and testing of novel vaccine adjuvants.

As espoused by the Global HIV Vaccine Enterprise, greater collaboration will be key to moving forward. As such, the Team Grant RFA includes requirements for ensuring that progress and results are communicated between and across funded teams. Teams are expected to gather at official meetings and symposia to share progress/challenges and have a presence at meetings of funded teams to be hosted by the CHVI Secretariat Meetings. Co-PIs and their respective teams in LMICs and Canada also expected to communicate with one another on regular basis. Proposals will be measured on their defined strategies for ensuring ongoing linkages within teams and between funded teams to be described within the proposal.

The same criteria which are used to review CIHR Team Grants in general will be applied to these international teams. These include:

• proposals address an important health and disease, health care or health system problem or issue;
• excellence of research proposed;
• applicants' productivity, experience and training;
• appropriateness of the Team;
• value added of funding through a collaborative program;
• coherent, integrated and feasible research plan;
• training opportunities; and,
• problem-based approach to research.

In addition, the unique elements of this RFA will be judged during peer review. These include relevance and potential impact, collaboration and community involvement, technical merit, capacity building and ongoing learning.

This information was discussed over lunch by session participants who then returned to share their comments, concerns and suggestions.

Team Grant RFA Design - Feedback and Discussion

The afternoon discussion allowed potential applicants the opportunity to seek clarification and raise any concerns around shortcomings in the draft RFA. Feedback can be broken into three key topic areas.

Attracting and Retaining Young Researchers

Younger researchers do not have the established networks to form the partnerships necessary to apply for a grant under the current RFA. As a prevailing thoughts in HIV circles (as stated by both Dr. Bernstein during the session and by Dr. Anthony Fauci of the NIH in a recent article in Science) there is a recognition that opportunities for young investigators are few. Although the Team Grant program provides for training opportunities, authors of the RFA should also be mindful that young investigators also require support.

Supporting new ideas and approaches

The objective of the Team Grant program is to strengthen health research by supporting teams of talented and experienced researchers conducting high-quality research and providing superior research training and mentorship. The program emphasis is on the production of new knowledge, and the translation of research findings into improvements in health and the health care system. These results will be realized more rapidly and more efficiently through the Team Grant program than if the components were to be funded as a series of separate operating grants. These may be new or established teams. "New" teams must demonstrate that they have already developed at least an informal relationship with the intent to work together in the future. These grants are not intended to support the development or creation of new teams.

Questions emerged around the definition of "new" in this description and whether this program would allow emerging ideas room to be explored. Given the rapidly changing environment in HIV vaccine research, the RFA should ensure that no novel or new idea remains unexplored.

RFA Application Process and Program Delivery

Throughout the discussion, specific details regarding the application process and delivery elements were raised. These issues were based on the experiences of researchers currently engaged in other international partnerships, those knowledgeable of the Team Grant program as well as researchers new to the CIHR process. These comments and suggestions were broken down into two major groups; eligible costs and post-administration of grants. Eligible costs should allow for cohort maintenance and given the need in LMICs provide salary support for Principal Applicants in that country. The second discussion trend touched upon the challenges in meeting the post-administration requirements of a grant. These include ethics review and memoranda of understanding (MOU) amongst implicated institutions – both across Canada and internationally. The international nature of the teams will undoubtedly lead to extended timelines for completion and increased costs as issues such as intellectual property, technology transfer and ethics certification are resolved. Suggestions from funded researchers were to allow interim MOUs, ensure team composition includes experts in all domains, ex. Lawyers and patent experts, and to build solid contingency plans into the research plan itself. Participants urged CIHR to be as clear and detailed as possible on required elements within the RFA itself to help guide applicants during the proposal writing process.

Summary and Path Forward

The Partnership Development Forum provided a mechanism for researchers to meet with colleagues from different countries and explore the potential for international collaborations in the area of HIV vaccine research. The session allowed members of the research community the rare opportunity to meet face to face to share ideas and progress – which is one of the guiding principles of the CHVI.

Most importantly, the session offered CIHR and CHVI partners valuable insight and advice on the shortcomings and strengths of the draft Team Grant RFA. The feedback in the area of RFA design along with the observations on the application process itself will serve as a guide for the final version of the funding opportunity to be released shortly.