Vaccination is the best way to tackle AIDS, says Seth Berkley, but we must plan to ensure wide access once we find the vaccine
AIDS is the greatest public health crisis of our time. More than 40 million people are now living with the human immuno-deficiency virus (HIV) or full-blown acquired immune deficiency syndrome (AIDS), and 14,000 more people are infected every day. It is critical that global initiatives that address the AIDS epidemic incorporate both a short-term and a longer-term perspective. Over the short term, we must do all we can to slow the epidemic by scaling up prevention programmes as well as coping with the consequences of today’s infections by providing treatment and care. Over the longer term, we need to support the development of better preventive tools, especially a vaccine, which has been key to ending viral epidemics.
Ending the AIDS epidemic is one of the greatest international challenges that we face, and a vaccine is the world’s best hope. Success will require a global response in which the public and private sectors adopt new ways to work together, building on each other’s strengths. The private sector is noted for its efficiency but requires market forces to operate. Given that more than 95% of the new HIV infections are occurring in developing countries, that the science is difficult and AIDS is politically controversial (at least in terms of stigma, sexual norms, intellectual property and expectations of acceptable profitability), we cannot rely on private sector solutions alone. The public sector, though often slow and less efficient, is called upon to solve problems where there is no market solution.
Vaccine not cure
The International AIDS Vaccine Initiative (IAVI) was established as a not-for-profit, public-private partnership in 1996 with this goal in mind. IAVI’s mission is to ensure the development of a preventive vaccine that will be accessible to all. Since its founding, IAVI has grown into the world’s largest organization focused solely on seeking out an AIDS vaccine, now operational in 23 countries. IAVI provides a global voice for the development of a vaccine and works to help advance scientific progress. With our partners, we have taken five candidate vaccines into human trials in eight countries. Three-quarters of IAVI’s scientific staff comes from the vaccine or biotechnology industry, and IAVI now operates as a fully integrated virtual vaccine company.
Vaccines rank among the most cost-effective public health interventions. Strong evidence exists from primates and humans that a vaccine to prevent the spread of HIV is scientifically possible. However, vaccines have not, until recently, been a priority. Spending on AIDS vaccine research and development (R&D;) grew from roughly $160 million in 1996, according to the Rockefeller foundation, to some $550 million, by our reckoning, in 2002. Even today, the world spends less than 2% of its AIDS effort on developing a vaccine. The AIDS vaccine effort represents less than 1% of total global spending on health R&D; annually. If a vaccine is to become a reality in the near future, we must significantly expand the level of political and financial support globally, and ensure that adequate resources are strategically targeted to priority areas.
Currently more than 30 candidate AIDS vaccines are in early human clinical trials. These are designed to elicit a type of anti-HIV immune response called cell-mediated immunity. A few look promising. However, there is too much duplication and not enough innovation. It is critical to develop other approaches, for example to bring the immune system’s second defence – antibodies – to bear on the problem. Through a novel research approach, a number of academic scientists and company and government researchers have come together in virtual consortium in an IAVI-sponsored initiative to solve this problem. The consortium is run by industrial project managers and pools core resources. Detailed structural analysis, high throughput assays and robotic technologies – only possible in the past few years – are giving the teams important clues for new designs and mechanisms to create them.
IAVI manages a diverse portfolio of vaccine projects to maximize our probability of success. The quickest route to a safe and effective vaccine is to pursue multiple paths in parallel and not sequentially. Our job is to survey academia, biotech and pharmaceuticals companies globally to find the best products; partner with the companies and scientists engaged; and work in partnership with investigators in the developing world. For each project the goal is to accelerate its development in order to make go/no go decisions as soon as possible and so keep a pipeline of candidates moving.
One of IAVI’s core principles is the need to engage the private sector. Most product development expertise rests in private companies. These companies have traditionally played the lead role in translating important basic research – which is mostly carried out by government research agencies and academic institutions – into products that can be manufactured on a large scale for commercial use. But in the case of vaccines, there is little incentive for private companies to invest heavily. With an AIDS vaccine, the problem is compounded because the potential market in industrialized countries is limited and may be influenced by political factors as well as the fact that the largest demand will be in countries least able to pay.
More must be done to engage the private sector in AIDS vaccine research and development. Public policies aimed at increasing private sector involvement are critical. IAVI and its worldwide partners have advocated legislation to implement a combination of push and pull mechanisms to spur new vaccine development. Push mechanisms, such as subsidies, tax credits and other incentives, reduce the risk by supporting the cost of R&D; for private companies. Pull mechanisms, such as creating an advance guarantee from funders that resources will be available to purchase and deliver a vaccine once it is developed, also reduce risk and might increase rewards. The challenge is to create incentives that will be sufficiently attractive to industry on the one hand, and politically feasible on the other.
A greater commitment from the private sector would help increase the number and diversity of vaccine candidates in the pipeline. These candidates must be tested in different populations and regions, particularly in developing countries, where different subtypes of the virus are circulating. Conducting large-scale efficacy trials in developing countries requires significant preparation, including the recruitment of thousands of volunteers at high risk of HIV infection. To facilitate recruitment, education and advocacy, IAVI is working with partners worldwide to increase knowledge and understanding of the potential benefits and risks associated with participation, and to prevent potential discrimination against trial participants within the community due to their perceived association with HIV.
Worthless unless available
Once an AIDS vaccine is successfully developed, formidable barriers stand in the way of rapid global access to it. These are political and logistical rather than scientific challenges. Overcoming them will require new forms of political commitment and leadership. IAVI has worked with the World Economic Forum and its Global Health Initiative to plan projects to bring attention to these challenges and to work on forging solutions. Historically, vaccines have taken up to 25 years or longer to reach low-to-middle income countries where they are most needed. The world must begin planning now for the rapid and widespread delivery and uptake of an AIDS vaccine to avoid the delays in access that have occurred with other vaccines.
There are a number of issues related to access. For example, regulatory oversight is necessary to ensure that only safe and effective products reach the consumer. However, today’s regulatory systems are not geared to facilitate rapid global access to AIDS vaccines. Traditionally, there is a gap of several years between initial licensing in an industrialized country and widespread licensing in developing countries. Action by regulatory agencies to streamline and coordinate dossier requirements and submission processes, and develop fast-track approval for life-saving products would significantly accelerate access and lower costs. Some progress has been made in standardizing regulatory approaches in Europe, Japan and the United States; more can be done to expand such efforts, especially in the developing world.
To secure an adequate supply, it will be critical to create adequate manufacturing capacity to meet the global need. Cooperation between the public and private sectors will also be necessary here. Billions of dollars will be needed to purchase and deliver an AIDS vaccine for use in low- and middle-income countries. Much of this funding will need to come from donor governments, multinational funding bodies such as the Global Fund to Fight AIDS, TB and Malaria, and multilateral organizations such as the World Bank. Cooperation between the public and private sectors will also be critical in building manufacturing capacity.
Distribution challenge We will also need to focus on distribution. Unlike current vaccination programmes, which primarily target children, initial AIDS vaccination efforts will be geared toward high-risk adults and adolescents, populations that are difficult to reach through current delivery mechanisms. It is vital for manufacturing, distribution and financing reasons to obtain estimates of how many people would be willing to receive and pay for a vaccine. IAVI and others have begun studies to forecast demand.
A comprehensive delivery strategy must include transportation; venues for delivering vaccines (clinics, mobile units and community settings); storage facilities; maintenance of the cold chain (if the vaccine requires refrigeration); education and marketing appropriate to specific populations; and linkages between voluntary counselling and testing, and vaccine delivery. Preparing for access should also include action to build necessary human resources.
Efforts to accelerate the development and swift global introduction of a preventive AIDS vaccine must be part of any comprehensive response to the epidemic. IAVI is committed to working with the public and private sectors in both industrialized and developing countries to mobilize the best human, technical and financial resources for this effort.
Solving this problem can serve as a model for how to bring public and private expertise together to resolve great scientific challenges of our times. Many of our great health and social problems may be amenable to technical solutions but will not have adequate market incentives driving them. Finding innovative ways to work together to make this happen is a critical task for us all.
Seth Berkley, president and founder of the International AIDS Vaccine Initiative, is a doctor specializing in infectious disease epidemiology and international health.