Health In Action African AIDS Vaccine Programme for a Coordinated and Collaborative Vaccine Development Effort on the Continent Pontiano Kaleebu*, Alash’le Abimiku, Shenaaz El-Halabi, Sinata Koulla-Shiro, Nicole Mamotte, Souleymane Mboup, Roy Mugerwa, John Nkengasong, Coumba Toure-Kane, Tim Tucker, Douglas Wassenaar, Carolyn Williamson, Dawit Wolday

early 30 years after the first Summary Points with candidate vaccines that were not cases of AIDS were reported based on strains circulating in Africa. sÈ 4HEÈ!)$3ÈPANDEMICÈCONTINUESÈTOÈ [1] and HIV identified as the AAVP was created with the specific N be the most serious public health causative agent, Africa today bears a intention of mobilizing support and challenge facing the world today, disproportionate burden of the disease. advocating for a more Africa-focused and Africa bears an overwhelming Sub-Saharan Africa has just over 10% vaccine agenda. In 2000, representative proportion of infections, with of the world’s population but is home African scientists met in Nairobi to unprecedented medical and to more than 65% of the 33 million create AAVP and issued a declaration— socioeconomic consequences. people in the world estimated to be “An African Appeal for an AIDS living with HIV/AIDS. The annual rate sÈ 4HEÈBESTÈHOPEÈTOÈENDÈTHEÈ!)$3È Vaccine” [5]. of new infections continues to rise, with pandemic remains the development The mission of AAVP is to advocate an estimated 2.5 million people newly of an effective HIV vaccine, and its for and support a coordinated infected in 2007 [2]. distribution to all communities. international effort to promote Although newer initiatives aimed sÈ 4HEÈ!FRICANÈ!)$3È6ACCINEÈ0ROGRAMMEÈ the development of and future at providing universal access to (AAVP), formed in 2000, is a network of access to HIV vaccines suitable for antiretroviral therapy in Africa are African HIV vaccine stakeholders, led ongoing, most Africans receive neither by Africans across the continent, with a Funding: AAVP is funded by CIDA Canada, SIDA/ treatment nor adequate care [3]. vision of an African continent without SAREC Sweden, and WHO/UNAIDS. These funders Relatively few HIV-infected patients in AIDS. had no role in the decision to submit this article for sub-Saharan Africa (about 1 million) publication or in its preparation. The authors received sÈ !!60ÈSUPPORTSÈANDÈREPRESENTSÈ no specific funding for this article. are currently receiving antiretroviral the diverse African communities treatment [4], and many more new Competing Interests: Tim Tucker was the consultant involved in HIV vaccine research contracted to develop the AAVP strategic plan. He cases are occurring each year [2]. It is and development (R&D), and is an received a fee for this. However, this was completed thus evident that treatment alone will important unified voice for African many months back, and he now has no financial not control the spread of the disease connection. There is no financial benefit to him in stakeholders. the publication of this article. We were unable to and that a vaccine is our best hope of contact Roy Mugerwa, listed as an author of this halting this pandemic. sÈ 4HISÈPAPERÈDESCRIBESÈWHATÈ!!60ÈIS È paper, before its publication. The corresponding In the history of infectious what it does, and its impact, successes, author, Pontiano Kaleebu, has stated that to the best and challenges. Finally, we discuss of his knowledge, Roy Mugerwa has no competing diseases, effective vaccines are critical interests. The remaining authors have declared that public health tools to control and where AAVP is heading to harmonize they have no competing interests. with the Global HIV Vaccine Enterprise prevent diseases. Developing an Citation: KaleebuP, Abimiku A, El-Halabi S, Koulla- effective HIV vaccine is proving to and the dynamic HIV vaccine research Shiro S, Mamotte N, et al. (2008) African AIDS Vaccine field. Programme for a coordinated and collaborative be one of the greatest challenges in vaccine development effort on the continent. PLoS biomedical research. The need for Med 5(12): e236. doi:10.1371/journal.pmed.0050236 a simple, safe, effective, affordable, This is an open-access article distributed under the and equitably distributed preventive with other more traditional prevention terms of the Creative Commons Public Domain HIV vaccine to complement existing declaration, which stipulates that, once placed in the interventions. public domain, this work may be freely reproduced, HIV/AIDS prevention, treatment, distributed, transmitted, modified, built upon, or and care programs is greater than What Is AAVP? otherwise used by anyone for any lawful purpose. ever. It is probable that vaccines An African response—the genesis Abbreviations: AAVP, African AIDS Vaccine will form part of future innovative AAVP was created in 2000 Programme; CC, collaborative center; R&D, research of AAVP. and development; SC, steering committee; UNAIDS, interventions including microbicides within the global context of relatively Joint United Nations Programme on HIV/AIDS; WHO, and circumcision, used in conjunction little attention being paid to Africa’s World Health Organization need for an HIV vaccine. While an HIV * To whom correspondence should be addressed. vaccine has always been considered a E-mail: [email protected] The Health in Action section is a forum for individuals global public good, most laboratory Author affiliations are listed at the end of the article. or organizations to highlight their innovative and clinical activities prior to 2000 were approaches to a particular health problem. Provenance: Not commissioned, externally peer conducted in the industrialized world reviewed

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Figure 1. The AAVP Structure GTN, Global Training Network. use in Africa. To meet the vision the field of HIV vaccines. The SC AAVP operates and implements most of an AIDS-free Africa through advises the secretariat on unique of its activities through a network of an effective vaccine, AAVP has opportunities for collaboration, and collaborative centers (CCs), located at strengthened the network of African provides strategic directions for AAVP. key institutions across the continent, HIV vaccine stakeholders through The SC also has representation from selected for their extensive experience research, advocacy, partnership, and the international partners to facilitate and comparative advantages to AAVP contribution to capacity strengthening networking, promote transparency, and and their ability for technology transfer and policy development. AAVP aims consolidate global involvement. within the continent. There are five to ensure that African communities and Africans participating in the HIV vaccine development process are adequately supported, are well represented globally, and are equal partners playing a critical role in HIV vaccine development efforts. AAVP is supported by the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS). AAVP is a partnership-based network, committed to working closely with all HIV vaccine partners and sharing its resources and capacity, consistent with the Global HIV Vaccine Enterprise. AAVP has been successful in raising funds from different sectors and countries for its activities since its inception. AAVP (Figure 1) is coordinated by a secretariat and a steering committee (SC). The secretariat is housed by the WHO Initiative for Vaccine Research and its HIV Vaccine Initiative, with plans for relocation to an African center in the future. This future secretariat will maintain close ties to WHO, but will also have strong collaborations and links to the Global HIV Vaccine Enterprise activities and planned secretariat in Africa. The doi:10.1371/journal.pmed.0050236.g002 AAVP SC is an advisory body comprised of senior African stakeholders in Figure 2. AAVP Strategic Directions and Work Areas

PLoS Medicine | www.plosmedicine.org 1654 December 2008 | Volume 5 | Issue 12 | e236 are able to respond to relevant research questions and have the skills to secure further national and international funding in collaboration with their counterparts in the developed world. AAVP also assists countries with the development of country-specific vaccine R&D plans and ensures that these are integrated as part of the overall national AIDS control program of each country. Finally, AAVP focuses on increasing the capacity of stakeholders on the continent to communicate more effectively on HIV vaccines. Specific Projects, Impact, and Successes AAVP achievements. Since its inception, AAVP has contributed doi:10.1371/journal.pmed.0050236.g003 significantly to a new level of visibility for African HIV vaccine activities and Figure 3. African Countries Participating in HIV Vaccine Trials has played an important coordinating and networking role on the continent. CCs, which reflect AAVP’s primary work African solutions across the diverse AAVP has brought together various areas: (1) regulatory issues; (2) ethics, cultural and political environment on African HIV vaccine stakeholders from law, and human rights; (3) biomedical the continent. Africa’s participation many countries, creating collaborations research; (4) country-based strategic must include all aspects of vaccine and training programs and organizing planning; and (5) communication and development: laboratory research, symposia addressing key issues relevant media. Table 1 shows their location vaccine and trial design, cohort to Africa. One year after its formation, and key functions. All CCs are guided development, advocacy, ethical, and in the 2001 Abuja Declaration on HIV/ by the following strategic directions: regulatory issues, and projections and AIDS, Tuberculosis, and Malaria, the capacity strengthening, advocacy, policy strategies for use of any possible HIV African Union Heads of State and development, increased community vaccine. AAVP also has the advantage Government committed themselves involvement, and networking (Figure 2). of impartiality in that it has no specific to supporting the development of To ensure AAVP is adequately products in development itself; AAVP’s an effective, affordable, accessible represented at a political level, close linkage to WHO/UNAIDS with HIV vaccine relevant to Africa. They Madame Jeannette Kagame, First their experience in ethics, regulatory, also pledged to support AAVP and Lady of Rwanda, has been appointed and policy issues gives it greater its partners and institutions devoted as AAVP’s “High Representative.” leverage in this regard. to HIV vaccine research and testing She is well versed in the issues of Operating through the five CCs, in Africa. This event, similar to the poverty-associated diseases, and has a AAVP addresses identified gaps, such as endorsement of the Global HIV high profile within Africa. The High the lack of adequate global regulatory Vaccine Enterprise by the G8 [6], Representative is expected to drive capacity and harmonization, which is is significant, as it was the first time the program at a political level and a major impediment to the conduct African leaders collectively and strongly act as AAVP’s “Ambassador” at various of properly reviewed and monitored, endorsed a continent-based vaccine meetings and policy forums. The AAVP high-quality HIV vaccine clinical effort. High Representative will work closely trials. AAVP also recognizes that To date, AAVP has successfully with the AAVP secretariat, the AAVP the development of an HIV vaccine expanded and increased training CCs, the secretariat of the Global HIV requires significant attention to ethics, and capacity building in the areas of Vaccine Enterprise, and the relevant law, and human rights, and works at the community and media education, WHO structures that are set up to interface of these fields with behavioral ethics, laboratory, and good clinical influence and advocate for countries— sciences to address the key issues in and regulatory practices specific to HIV e.g., the WHO External Relations HIV vaccine R&D and trials. vaccine development. AAVP has also Officer and the New Partnership for Furthermore, the AAVP vision provided support to the development African Development (NEPAD; http:// requires that Africans be integral to of national AIDS vaccine plans in www.nepad.org/) Focal Point. all aspects of vaccine development. Botswana, Cameroon, Côte d’Ivoire, Increased African participation in HIV Ethiopia, Kenya, Nigeria, Rwanda, What Does AAVP Do? vaccine-related biomedical research Tanzania, Uganda, and Zambia, and to As a network of African stakeholders is critical for true partnership and the involvement of community groups in vaccine development, AAVP has the trust. AAVP strengthens and develops in preparation for HIV vaccine trials. comparative advantage of being in a a broad base of African biomedical AAVP has been instrumental in the unique position to provide common scientists and research clinicians, who development of regional networks and

PLoS Medicine | www.plosmedicine.org 1655 December 2008 | Volume 5 | Issue 12 | e236 Table 1. AAVP Collaborating Centers, Location, and Key Functions Collaborating Center Location Key Functions

Regulatory issues Not yet determined; applications are requested sÈ Needs assessment and training of regulatory bodies in countries where HIV to host this Center vaccine trials are already being conducted or where they are planned sÈ Working with the various African and non-African regulatory bodies and international HIV vaccine developers to ensure that training courses and policy development programs are appropriate for developing country regulators sÈ Working with WHO and regional regulatory bodies to advise on potential harmonization of regulatory processes Ethics, law, and human rights School of Psychology, University of KwaZulu- sÈ Networking and assessment of needs for capacity building and training Natal, Pietermaritzburg, South Africa sÈ Development of policy and guidance documents and training of IRBs in Africa sÈ Publications and REC/IRB training on key ethical issues relevant for Africa sÈ Conducting research into development of a model ethical-legal framework Biomedical research Hosted by a consortium of three institutions: The sÈ Assessment of research and training needs, focusing on countries involved in Laboratoire de Bacteriologie Virologie, Universite HIV vaccine-related research and clinical trials Cheikh Anta Diop CHU Le Dantec, Dakar, sÈ Training of African investigators and building of human and infrastructure Senegal; the Institute of Infectious Disease and capacity Molecular Medicine, University of Cape Town, sÈ Networking and support for selected research projects to generate information South Africa; and the Uganda Virus Research relevant for Africa Institute, Entebbe, Uganda Dissemination of biomedical information across the continent Country-based strategic planning WHO secretariat, Geneva, SwitzerlandsÈ Support for strategic planning and the development of national HIV vaccines plans sÈ Development of a guidance document as a tool to help countries with their national HIV vaccine plans Communication and media ACE Communication and Media, University of sÈ Training for media and communication representatives, especially community Nairobi, Kenya representatives sÈ Development of targeted communication and education tools sÈ Links and networking between Anglophone, Francophone, and Lusophone African countries sÈ Linking of African trial site communities involved in HIV vaccines, so as to facilitate sharing of information and experience on community-based issues in the field

IRB, institutional review board; REC, research ethics committee doi:10.1371/journal.pmed.0050236.t001 collaborative partnerships with African far more focused on countries most as well as to work with more relevant HIV vaccine research stakeholders. affected by the HIV pandemic, and vaccine technology platforms and It has facilitated an international investment in Africa has increased HIV gene inserts. The move to shift discussion of the inclusion of significantly. In addition, there has greater financial support to developing adolescents in HIV vaccine trials [7], been a shift by vaccine developers countries has required increased identified capacity needs of 35 African towards vaccine candidates that better capacity development and political research ethics committees to review reflect the HIV-1 variants prevalent in support within developed countries. HIV vaccine trials [8], and developed Africa. One indicator of the increased Second, the significant shift in global discussion documents on topics such focus on Africa can be seen in the thinking associated with the Global as enrollment of women in trials number of countries conducting HIV Vaccine Enterprise has changed [9], intellectual property, and tissue HIV vaccine trials. Only one country the field. The Enterprise is an alliance transfer issues [10]. AAVP has provided (Uganda) had conducted an HIV of independent global HIV vaccine technical and financial support to ten vaccine clinical trial prior to 2000 development partners, all of which research projects implemented by [12], whereas by 2007, eight African have their own work plans, but share young African scientists (e.g., [11]). In countries had conducted HIV vaccine a commitment to working together addition, AAVP has organized three trials (http://www.iavireport.org/) in a more efficient, collaborative, and forums to facilitate interaction between (Figure 3). In addition, the level of complementary manner to develop an partners and stakeholders for the political support has also increased in HIV vaccine in the shortest possible development of common policies and many African countries. time (http://www.hivvaccineenterprise. strategies and their integration into the Global changes in the field of org/) [13]. global vaccine agenda. HIV vaccines, to which AAVP has responded, have occurred within Where Is AAVP Heading? Challenges two major contexts. First, there has In the next two to three years, Changes in the global HIV vaccine been a growing understanding by AAVP will become an autonomous environment. Since the creation the international community of organization, with its secretariat of AAVP in 2000, there have been the need to work more closely with based in Africa but with strong links dramatic changes in the African and scientists, clinicians, communities, to WHO/UNAIDS and the Global global HIV vaccine context. The HIV politicians, and other stakeholders in HIV Vaccine Enterprise. This move vaccine R&D agenda has become highly affected regions of the globe, will bring AAVP closer to its partners

PLoS Medicine | www.plosmedicine.org 1656 December 2008 | Volume 5 | Issue 12 | e236 working in Africa and to African Acknowledgments References leadership, and will increase African 1. Gottlieb MS, Schroff R, Schranker HM, We are very grateful to Dr. Marie-Paule Kieny, Weissman JD, Fan PT, et al. (1981) ownership. The CCs will be central Pneumocystis carinii pneumonia and mucosal Dr. Saladin Osmanov, Ms. Coumba Toure, to AAVP’s activities, acting as hubs candidiasis in previously healthy homosexual Dr. Madani Thiam (up to 2006), and Belinda men: Evidence of a new acquired cellular bringing together partners to address Hall at the WHO/UNAIDS HIV Vaccine immunodeficiency. N Engl J Med 305: 1425- a shared plan aligned with the Global Initiative, Geneva for their contribution in 1431. HIV Vaccine scientific plan. While 2. UNAIDS/WHO (2007) 2007 AIDS epidemic the drafting of this manuscript and for their update. Available: http://www.unaids.org/ biomedical research, communication continued administrative support. We are en/KnowledgeCentre/HIVData/EpiUpdate/ and media, ethics, law, and human also grateful to the following past members EpiUpdArchive/2007/default.asp. Accessed 6 rights, and regulatory issues will be of the AAVP Steering Committee and former November 2008. 3. Dionisio D, Cao Y, Hongzhou L, Kraisintu K, based at the CCs with coordination at WHO staff for their contribution to the Messeri D (2006) Affordable antiretroviral the secretariat, country-based strategic development of AAVP, namely Professor drugs for the under-served markets: How to planning will remain an activity of the Fred Mhalu, Professor Dundu Owili Malaki, expand equitable access against the backdrop Professor William Makgoba, Dr. Thior Ibou, of challenging scenarios? Curr HIV Res 4: 3-20. secretariat working closely with WHO/ 4. UNICEF/UNAIDS/WHO (2007) Towards and Dr. José Esparza. Lastly we thank all the UNAIDS. An important strategic universal access: Scaling up priority HIV/AIDS funders of the AAVP activities, especially interventions in the health sector. Available: objective for AAVP will be to influence CIDA Canada, SIDA/SAREC Sweden and http://www.who.int/hiv/mediacentre/ the global agenda for HIV vaccine WHO/UNAIDS. universal_access_progress_report_en.pdf. R&D and, at the same time, to create Accessed 29 October 2008. Author affiliations. Pontiano Kaleebu is 5. WHO (2000) The Nairobi Declaration: An stronger ties and partnerships between with the Uganda Virus Research Institute, African appeal for an AIDS vaccine. Available: African researchers and institutions Entebbe, Uganda (MRC/UVRI Uganda http://www.who.int/vaccine_research/ Research Unit on AIDS and UVRI- diseases/hiv/en/JC469-NairobiDeclar-E.pdf. and the rest of the world. To that end, Accessed 29 October 2008. AAVP will explore the possibility of IAVI HIV Vaccine Program). Alash’le 6. Vogel G (2004) AIDS vaccines. G8 leaders a close relationship with the Global Abimiku is with the Institute of Human endorse global effort. Science 304: 1728. Virology-Nigeria, Plateau State Human 7. WHO/UNAIDS/AAVP International Expert HIV Vaccine Enterprise as a vehicle Virology Research Center, Jos, Nigeria. Group, Osmanov S (2007) Executive summary and recommendations from WHO/UNAIDS for positioning African HIV vaccine Shenaaz El-Halabi is with the Ministry research internationally. and AAVP consultation on: ‘The inclusion of of Health of Botswana, Health Research adolescents in HIV vaccine trials’, 16-18 March In summary, AAVP acts to serve the Unit, Gabarone, Botswana. Sinata Koulla- 2006 in Gaborone, Botswana. AIDS 21: W1- network of African stakeholders in the Shiro is with the Faculty of Medicine and W10. 8. Milford C, Wassenaar D, Slack C (2006) major global mobilization to discover Biomedical Sciences, University of Yaoundé, Resources and needs of research ethics an effective HIV vaccine. AAVP is Yaoundé, Cameroon. Nicole Mamotte and committees in Africa: Preparations for HIV entering a new phase of increased Douglas Wassenaar are with the School of vaccine trials. IRB 28: 1-9. Psychology, University of KwaZulu-Natal, 9. Wassenaar DR, Barsdorf NW (2007) The activities and exposure, subsequent to ethical involvement of women in HIV vaccine Pietermaritzburg, KwaZulu-Natal, South comprehensive external review and trials in Africa: Discussion paper developed for Africa. Souleymane Mboup and Coumba strategic planning processes. the African AIDS Vaccine Programme. Women Toure-Kane are with the Laboratoire de Health 45: 37-50. AAVP is firmly positioned to play Bacteriologie Virologie, Universite Cheikh 10. Andanda P (2008) Human-tissue related a significant leadership role on the inventions: Ownership and intellectual Anta Diop, Dakar, Senegal. Roy Mugerwa is property rights in international collaborative African continent as the voice of with the Department of Medicine, Makerere research in developing countries. Discussion African stakeholders involved in University, Kampala, Uganda. John paper developed for the African AIDS Vaccine HIV vaccine development. AAVP’s Nkengasong is with the Centers for Disease Programme. J Med Ethics 34: 171-179. 11. Ndembi N, Lyagoba F, Nanteza B, plans are responding to the changing Control and Prevention, Atlanta, Georgia, Kushemererwa G, Serwanga J, et al. (2008) HIV vaccine environment, and offer United States of America. Tim Tucker is with Antiretroviral drug resistance surveillance substantial added value to those the Scientific Medical Research (Pty) Ltd, among newly HIV-1 diagnosed women Cape Town, Western Cape, South Africa. attending antenatal clinic in Entebbe, Uganda. working in Africa by focusing on AIDS Res Hum Retroviruses 24: 889-895. Carolyn Williamson is with the Institute of areas where AAVP has a comparative 12. Mugerwa RD, Kaleebu P, Mugyenyi P, Infectious Diseases and Molecular Medicine, Katongole-Mbidde E, Hom DL, et al. (2002) advantage. AAVP looks forward to the University of Cape Town, Cape Town, First trial of the HIV-1 vaccine in Africa: next five years of enhanced activities Western Cape, South Africa. Dawit Wolday Ugandan experience. BMJ 324: 226-229. and greater impact towards its vision 13. Klausner RD, Fauci AS, Corey L, Nabel GJ, is with Medical Biotech Laboratories, Addis Gayle H, et al. (2003). The need for a global of “an AIDS-free Africa through an Ababa, Ethiopia. After the first author, HIV vaccine enterprise. Science 300: 2036- effective vaccine.” authors are listed in alphabetical order. 2039.

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