Science

Since it was identified three decades ago, HIV has infected more than 78 million people worldwide and has killed half of those it has infected. Antiretroviral drugs have made AIDS treatable for those who have access and adhere to it, and — by reducing viral load in blood — can reduce the risk of transmission to others. However, only 45% of those living with HIV in low- and middle-income countries who are eligible for treatment under the current guidelines by the World Health Organization actually access treatment. In 2013, 1.5 million people worldwide died from AIDS-related causes, and 2.1 million people newly contracted HIV.

Vaccine researchers worldwide are working relentlessly toward training the immune system to prevent new infection with HIV or to control or even clear existing infection. A vaccine that controlled infection would reduce viral load and thereby avoid or delay progression to AIDS, and also reduce the risk of transmission to others.

  • Sub-Saharan Africa is the epicenter of the global AIDS epidemic. About 68 percent of the almost 6,000 people worldwide infected each day with HIV are living in Sub-Saharan Africa. About 19 percent of people in South Africa and 27 percent in Swaziland are living with HIV. In Eastern Africa, prevalence in the general population can still reach 5 to 7 percent, and can be several times higher among commercial sex workers, men who have sex with men, transgender people and highly mobile communities such as fisher folk around Lake Victoria. Of the 3.2 million children worldwide under the age of 15 living with HIV, 91 percent live in Sub-Saharan Africa. Incidence in young women and girls in sub-Saharan Africa is up to five times that of men and boys their age.
     
  • HIV mutates more rapidly than most other viruses, escapes the immune system’s responses and exists in different strains globally. Only a few people live with untreated HIV without progressing to AIDS (long-term non-progressors); their immune systems are able to fully contain HIV for decades. In most cases however, HIV establishes persistent infection very quickly after transmission and hides in reservoirs from which it can strike again at any time – so the opportunity for a vaccine to prevent or control initial infection is short-lived. An effective HIV vaccine likely will need to induce both arms of the adaptive immune system, antibodies and killer T cells, to prevent infection with HIV and progression to AIDS.

  • Broadly neutralizing antibodies found in about 5% of the people living with untreated HIV (elite neutralizers) can neutralize many if not all of the many HIV variants in laboratory experiments and in monkeys, and may be able to prevent new infection with HIV. Broadly neutralizing antibodies have cleared existing infection in some monkeys. Research has also shown that killer T cells (CD8+) can control HIV replication in both acutely infected people and long-term non-progressors, and as part of an effective vaccine may play an important role in preventing new or clearing initial infection. However, HIV’s huge variability and capacity to play hide and seek with the immune system continue to pose significant challenges to the design of an effective vaccine. The VISTA partnership proposes to address some of these challenges.

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A VISTA Program Steering Committee (PSC) composed of the Principal Investigators of the participating Clinical Research Centers and representatives of IAVI and Emory oversees the program. IAVI’s Scientific Advisory Committee provides strategic and scientific advice. The charter for the PSC is being developed. The Scientific Strategy Group (SSG) identifies and further develops the scientific goals and plan, and is responsible for implementation. The program will include several projects and project teams.

 

VISTA Scientific Strategy Group

The VISTA Scientific Strategy Group is made up of the following experts:

Virology — led by This email address is being protected from spambots. You need JavaScript enabled to view it., Professor of Systems Biology and Scientific Director of the HIV Pathogenesis Program, University of KwaZulu Natal, South Africa and This email address is being protected from spambots. You need JavaScript enabled to view it., Professor of Microbiology and Immunology and Co-Director, Emory Center for AIDS Research, Emory University, Atlanta, GA, USA

Immunology — led by This email address is being protected from spambots. You need JavaScript enabled to view it., Director of the Medical Research Center/Ugandan Vaccine Research Institute Research Unit on AIDS and Deputy Director Uganda Virus Research Institute, Entebbe, Uganda and This email address is being protected from spambots. You need JavaScript enabled to view it., Executive Director, IAVI Human Immunology Laboratory at Imperial College London, United Kingdom

Clinical — led by This email address is being protected from spambots. You need JavaScript enabled to view it.Projet San Francisco, Rwanda Zambia HIV Research Group, Kigali, Rwanda and This email address is being protected from spambots. You need JavaScript enabled to view it., clinical researcher, Kenya Medical Research Institute/Wellcome Trust, Kilifi, Kenya

 

VISTA Program Steering Committee

The VISTA Program Steering Group includes the leaders of the of the Scientific Strategy Group plus:

This email address is being protected from spambots. You need JavaScript enabled to view it., Director Kenya AIDS Vaccine Initiative Institute of Clinical Research (KAVI-ICR) at the University of Nairobi in Nairobi, Kenya

This email address is being protected from spambots. You need JavaScript enabled to view it., ‎Project Director, Zambia-Emory HIV Research Project (ZEHRP), Lusaka, Zambia

This email address is being protected from spambots. You need JavaScript enabled to view it., Deputy Director Research, The Aurum Institute, Rustenburg, South Africa

This email address is being protected from spambots. You need JavaScript enabled to view it., Executive Director, Uganda Virus Research Institute (UVRI) International AIDS Vaccine Initiative (IAVI) HIV Vaccine Program, Entebbe, Uganda

This email address is being protected from spambots. You need JavaScript enabled to view it., Deputy Director, Medical Research Council Uganda Virus Research Institute Uganda Research Unit on AIDS (MRC/UVRI), Entebbe, Uganda (chair)

 

Design and assess the next generation of AIDS vaccine candidates for Africa, with Africa, and make unique and complementary contributions to the broader field of AIDS vaccine research and development.

vista piechart 2015VISTA is a new initiative to strengthen and expand an international consortium of investigators in order to address gaps in HIV vaccine design. VISTA will extend knowledge using existing and new samples from unique cohorts of people across Africa. The partners are driven by shared research interests, their common desire to address important scientific needs, and their commitment to strengthening sustainable capacity and technical capability in early-stage research in eastern and southern Africa. The goal is to ensure that African scientists increasingly contribute to and take leadership in AIDS vaccine design and development.

At its inception, VISTA is building on over a decade of partnership and includes eight Clinical Research Centers in eastern and southern Africa; and the international collaborations and central support hubs with Emory University, Atlanta, USA (virology) and IAVI’s Human Immunology Laboratory at Imperial College London (immunology, and data and sample management). New partnerships have been developed with the Delhi-based HIV Vaccine Translational Research Laboratory, a collaboration between IAVI and the Indian Government. VISTA compliments and synergizes the efforts of IAVI's Neutralizing Antibody Consortium at the Scripps Research Institute and the IAVI Design & Development Laboratory. VISTA is open to the inclusion of other partners and aims to catalyze translational HIV vaccine research in East and Southern Africa.  

Advance Immunogen Design and Testing
VISTA aims to:

  • Further characterize how the immune system can control HIV across its diverse clades and the populations it affects the most
  • Help gain a deeper comprehension of the nature of the transmitted virus when one person infects another
  • Identify T cell specificities associated with broad and potent control of HIV infection in existing blood samples, and also in a newly developed laboratory test to analyze viral inhibition

Using these results, researchers will:

  • Identify critical sites of vulnerability on the virus
  • Fully assess the immune responses associated with these T cell specificities and vulnerable sites in volunteers who control HIV persistently
  • Help guide the design and assessment of next-generation immunogens to elicit broad and potent T cell responses against HIV through vaccination
  • Develop next-generation assays to better assess HIV vaccines in clinical trials

The development of new, more effective assays and relevant reagents will allow better understanding and characterization of both viral characteristics and immune responses, both of which are important for vaccine design. VISTA will develop assays to assess T cell responses, molecular characterization of HIV, and assess immune signatures for vaccine design studies and vaccine trials. VISTA will also include assay development to support a new type of experimental clinical trials of new immunogens to elicit both broad T cell responses and broadly neutralizing antibodies. As part of VISTA, African clinical research centers will perform exploratory clinical studies of immunogens to elicit broadly neutralizing antibodies. 

Strengthen Sustainable Capacity: Centers of Excellence, Training and Data Sharing
VISTA’s transfer and training program across the entire discovery and development pathway will strengthen existing capacity and capabilities in epidemiological research and clinical development and will build new capacity and capabilities in earlier stages such as virology, immunology and immunogen design.

VISTA will foster the development of centers of excellence across Clinical Research Centers in eastern and southern Africa, enhancing individual centers' expertise and capabilities in areas such as: functional viral inhibition assays using panels of diverse and well-characterized viruses from collaboration; mucosal sampling; epitope mapping; and viral gene sequencing.

VISTA will work with Indian partners to include participation of centers of excellence in India, thus enhancing South-South collaboration. The testing of immunogens to elicit broadly neutralizing antibodies will focus on immunogens developed in collaboration with Indian research institutions. Samples, reagents and capabilities will be shared across the consortium. Data and results will be shared openly between partners, and will be stored in a dedicated, common data warehouse. IAVI’s Human Immunology Laboratory at Imperial College London, along with Emory University will provide mentorship, training, core and data support, as well as develop and transfer reagents, assays and technology for immunology and molecular virology.

The program will also ensure that additional capacity is sustained and that next-generation African researchers and investigators are developed, engaged and empowered to participate in and eventually lead the development of an AIDS vaccine for Africa. In addition, VISTA will:

  • Fund new research positions at African sites
  • Encourage African postdoctoral scientists who have studied abroad to return to work in African research institutions
  • Provide training opportunities for African PhDs and postdoctoral fellows
  • Support development of competitive research proposals by African investigators for both domestic and international funding

Leveraging More Than A Decade Of Experience And Unique Samples
VISTA leverages more than a decade of close collaboration between IAVI and a network of eight African research partners, as well as the IAVI Human Immunology Lab at Imperial College LondonEmory University and Indian research institutions (including the HIV Vaccine Translational Research Laboratory). Through training, equipment and technology transfer, IAVI and partners have helped build and strengthen capacity and technical capabilities for epidemiological research and clinical development in eastern and southern Africa. VISTA draws upon the capabilities and assets of the network including samples and new data from acute HIV infection cohorts, vaccine trial samples and novel technology platforms.

VISTA will leverage samples from unique, increasingly rare cohorts of people in different stages or with various kinds of HIV infection, including people with acute infection or super infection (re-infection with one or more virus strains), long-term non-progressors and elite controllers (people who spontaneously control the virus in the absence of therapy). These cohorts span multiple HIV clades and groups of people, and provide a powerful resource for guiding multi-functional vaccine design and assessment. A key component is a collection of samples and data from Protocol C, a well characterized early HIV infection cohort of more than 600 volunteers (including volunteer with acute infection) with more than 5 years median follow-up. Protocol C data drive immunogen design through understanding the nature of the transmitted virus and resolution of acute infection. VISTA will also establish new cohorts to collect samples in the very early stages of infection with HIV and to examine these samples with new technologies.

The Clinical Research Centers in Africa have well-established accredited laboratories that have supported 15 phase I and II clinical trials of 26 AIDS vaccine candidates as well as numerous epidemiological studies. Through these programs accredited quality controlled laboratories, and access to unique and diverse cohorts and samples have been developed. Each center has full safety diagnostic laboratory capability, well equipped cellular and serology laboratories and bio-banking capabilities. The teams at Emory University and IAVI’s Human Immunology Laboratory at Imperial College London have and will continue to develop a series of technical platforms including high throughput full viral genome sequencing, viral replicative capacity assays and functional assays such as the CD8 T cell viral inhibition assay. IAVI further contributes experience and capabilities in advancing promising vaccine candidates into clinical development.

Structure and governance of VISTA

Project management and contact: This email address is being protected from spambots. You need JavaScript enabled to view it., Senior Director, Program Management, IAVI, Entebbe, Uganda 

Funding The work on Protocol C and G has been funded by an international consortium of development agencies including the generous support of the American people through the United States Agency for International Development (USAID) that also funds VISTA. The complete list of IAVI's donors can be found here.

Outwit HIV where it hits the most

CRP 042611 825-webCharlotte Raymond/IAVIIAVI’s R&D team designs and develops HIV vaccine candidates, and conducts vaccine trials and related epidemiological research in partnership with more than 100 academic, biotechnology, pharmaceutical and governmental institutions. Learn more about recent progress in HIV vaccine R&D

 

HIV Vaccine Approaches
Vaccinologists are working simultaneously on two primary approaches to preventing HIV infection: engaging the immune system to block infection and training it to recognize and destroy cells that have already been infected by HIV. Learn more

Vaccine Development Process
HIV vaccine candidates are put through a rigorous and lengthy process of clinical evaluation to establish their safety and efficacy. Learn more

Clinical Research Standards
IAVI and its partners subscribe to the highest scientific and ethical standards for conducting trials of HIV vaccine candidates, one that emphasizes protecting the rights, wellbeing and dignity of trial volunteers. Learn more

IAVI’s Portfolio
IAVI and its partners have translated groundbreaking technologies into AIDS vaccine candidates, of which 15 have been tested in 27 early-stage human trials in 11 countries on 4 continents. Learn more

Vaccine Immunology Science and Technology for Africa (VISTA)
VISTA is a new initiative to strengthen and expand an international consortium of investigators in order to address gaps in HIV vaccine design. Learn more

IAVI’s Global Scientific Network
IAVI and its partners have established a network of sophisticated laboratories and clinical research centers in Asia, Africa, Europe and North America. IAVI also has launched consortia to address the major scientific problems of HIV vaccine development and boost the number and quality of novel vaccine candidates evaluated in clinical trials. Learn more

Building Scientific and Technical Capacity in Developing Countries
A major portion of the vaccine research that IAVI supports is conducted in developing countries, where 95% of all new HIV infections occur. The organization prioritizes building technical and scientific capacity in these countries. Learn more