World Aids Vaccine Day, May 18th

Today, 33 million people are living with HIV/AIDS and almost 7,500 people are newly infected every day. Whilst the spread of HIV appears to have slowed down, given the recent revisions of the epidemiological figures by the UNAIDS and WHO, the motor behind this epidemic is still running. For each 2 persons starting on antiretroviral therapy, another 5 people become infected with HIV. Yet we know of a tool that can help us not only to bring down the numbers of newly infected people, but also to eradicate this virus from the world. This tool is an AIDS vaccine.

The costs for fighting HIV/AIDS are unsustainable

Developing an AIDS vaccine is a major scientific challenge, and a long-term effort, but we can’t afford to ever give up. The costs of providing life-prolonging treatment will continue to escalate. UNAIDS projected in September that the pricetag of universal access to AIDS prevention, treatment and care would be roughly $54 billion a year by 2015. Since then UNAIDS has revised its epidemiological figures downwards, but even with a 20 percent cost reduction, spending on AIDS would place a phenomenal burden on budgets for overseas development assistance.

Vaccines are powerful tools in fighting infectious diseases

No viral disease has ever been controlled without a vaccine. The history of infectious diseases acts as a powerful reminder of the extraordinary promise held by a vaccine. Smallpox was eradicated in 1977 through vaccination; the first infectious disease to ever be eliminated from the planet. Today, polio has been eradicated in most regions across the world, thanks to the discovery and worldwide delivery of a vaccine. Even a modestly effective AIDS vaccine could avoid millions of new infections (recent modeling conducted by IAVI shows that an AIDS vaccine with 50% efficacy used in 1/3 of the population would avoid 17 million new infections during the first 15 years following its introduction), thereby substantially increasing our chances to eradicate HIV.

Vaccines are one of the most effective public health interventions ever known. They are relatively cheap and can be distributed using rather basic health infrastructures. Moreover, AIDS vaccines have the potential to protect from both sexual and blood-borne transmission of HIV for a sustained period of time and before the sexual debut. Also, the distribution of AIDS vaccines is independent of any risk behavior, which could facilitate outreach to highly vulnerable and marginalized populations, such as commercial sex workers and injecting drug users.

Vaccines are powerful equity tools that can be initiated by women

Existing prevention tools for HIV/AIDS are only partially successful. Those available today, such as condoms and circumcision, are mostly controlled by men. Women, in particular, lack methods they can use and control to prevent themselves against HIV infection. New technologies are required that women can initiate, such as microbicides and vaccines. Vaccines are powerful equity tools, more easily accessible for women and the poor than most other medical interventions. AIDS vaccines could protect women and their children independently of a partners’ consent.

Scientific evidence suggests that an AIDS vaccine is possible

There are clearly documented cases of individuals who have been infected for 25 years or more and have shown no ill effects. If scientists can work out the type of immune responses that afford these “elite controllers” protection, then the hope is that researchers can replicate those with a vaccine. There are also documented cases of individuals who have been repeatedly exposed to HIV but have not become infected. Again, if scientists can define precisely how these individuals manage to be resistant to HIV infection, it might provide vital clues about how to create a vaccine. In non-human primates (NHPs) it is possible to provide protection against infection with SIV, an equivalent of HIV, with a live-attenuated vaccine (a vaccine that uses the entire virus). It is not considered safe to make vaccines for humans using the same approach. But by studying how this model works the AIDS vaccine field can gain clues about how to make a safe vaccine for humans. Finally, AIDS vaccine experts know that some individuals who are HIV infected produce broadly neutralizing antibodies. These are antibodies that will destroy the vast majority of types of HIV circulating in the world today. If researchers can figure out how to design a vaccine that would teach the body to make broadly neutralizing antibodies, there is hope we can design an effective AIDS vaccine for humans.

Important progress towards a safe and effective AIDS vaccine is being made

Over the past few decades considerable time and energy has been invested in developing and testing AIDS vaccine candidates, but the results so far have been disappointing. HIV and its strategies for infection have proven to be a much more complex than initially thought. Yet, the investments in research have unraveled a great number of secrets about this virus, and more is known about HIV than any other pathogen studied to date. Furthermore, AIDS vaccine studies, whilst not yielding a successful candidate, have informed researchers on how to design better vaccine candidates. Some of the critical lessons learned over the last years include:

• The milestone Merck and Phambili STEP trials which were halted in September 2007 have provided valuable lessons (on what does not work) and have marked a move away, at least in the short term, from large-scale trials, with funds shifting towards more discovery research
• There has been a significant improvement in our understanding of HIV: how it works and where some its vulnerabilities lie (though more secrets need to be unraveled in order to get to a vaccine).
• Studies with HIV´s sister virus, Simian Immunodeficiency Virus (SIV) have shown that protection is possible, and this research continues to provide information on what an AIDS vaccine needs to achieve in order to work.
• Ongoing research in two rare groups of individuals - those at risk of HIV infection but not contracting it and those who are infected but control the virus for many years, namely “elite controllers”, is providing important clues for the design of novel AIDS vaccine candidates.
• Important capacity for AIDS vaccine research has been established in developing countries. The contribution of these countries to the global research effort is critical - as the burden of AIDS is greatest there, as is the need for an AIDS vaccine - and is providing critical information for vaccine design.

AIDS vaccine research is still in its discovery phase, but with more resources being dedicated here, progress will be accelerated and more important breakthroughs may be expected, as well as the launch of promising new AIDS vaccine candidates in clinical trials.

Developing an AIDS vaccine is a long-term effort

The development of an AIDS vaccine is one of the greatest challenges currently in medical research, and is going to be a long-term effort. But this is not news. We know from history that other vaccines took many decades to develop. For example, it took scientists 42 years to develop a vaccine for chicken pox and 47 years to find one that protects against polio. AIDS vaccine research is still in its early years. Whilst HIV was discovered 25 years ago, a serious effort to develop a vaccine against this virus did not start until the mid-nineties. Today, more than a decade into this effort, we tested in clinical trials only 2 AIDS vaccine candidates for their ability to protect against HIV infection; both candidates failed. Such results are common when developing medicines or vaccines (it is estimated that only 1-5 to 1-10 products in advanced clinical development ultimately make it to market).
Scientists don’t know how long it will take to develop an AIDS vaccine. We do know from history that a vaccine is the only way to end a major viral epidemic and that perseverance and long-term investment are necessary to develop a vaccine. It is certainly true that developing an AIDS vaccine has proven more difficult than researchers imagined when they first set out on the mission decades ago. But nobody entered this field thinking this was easy work. On the other hand, every researcher involved knew it was vital, and it remains more so today than anyone could have imagined 25 years ago.

There are important benefits in the journey towards an AIDS vaccine

Whilst we do not yet have an AIDS vaccine, the money spend on this research so far has brought us much closer to such a vaccine. From a scientific perspective, we did learn over the last years what it takes to make a safe and effective HIV vaccine. The challenge now is turning this knowledge into designing the right vaccine. And we should not forget what investing in HIV vaccine research means for the broader vaccine field. HIV is the most complex virus we know today. It has forced us to look at new technologies on how to make vaccines; the classical methods turned out to be insufficient. The new technologies that we are developing now will help us also to improve the development of current vaccines, for example against flu and tuberculosis.

The money spend on HIV vaccine research has also helped researchers and communities in developing countries. Their contribution towards developing an AIDS vaccine has resulted in the building of research laboratories and clinics, in training scientists and healthcare staff, and in providing thousands of volunteers with education on HIV prevention and access to HIV testing. Such achievements make investing in AIDS vaccines even more worthwhile; not only the end-goal, but also the journey to reaching it provides benefits to those most affected by HIV.

The discovery of an AIDS vaccine needs innovation in science

We need to diversify our approach and design new vaccine concepts. Currently nearly all AIDS vaccine candidates in development are based on the same idea: activating the T-cell arm of the immune system. T-cell vaccines may suppress the amount of virus circulating in those who become HIV infected after vaccination, thereby slowing progression to AIDS and potentially reducing the risk of transmission. However, it is thought that these vaccines are unlikely to protect individuals from becoming infected in the first place. Many scientists believe that to prevent infection altogether a vaccine will also have to activate the other arm of the immune system, B-cells that can generate neutralizing antibodies to HIV. Considerable work still needs to be done unlocking the mysteries of neutralizing antibodies before an AIDS vaccine can be developed based on this design.

A number of scientific consortia have been established in recent year to address this and other challenges blocking the path to success. These consortia bring together scientists and product development specialists from across the world, and focus on solving a particular scientific question. More recently, a number of organizations including the Bill and Melinda Gates Foundation and the International AIDS Vaccine Initiative launched Innovation Funds promoting out-of-the-box ideas to solve key scientific challenges, foster innovation and accelerate progress.

Innovation in the way we do research is urgently needed

Besides scientific innovation, we also need innovation in the way we do research and development. Traditionally the R&D process is compartmentalized, with different stages lead by different actors, including academia, biotech and pharmaceutical companies and manufacturers. While this system acknowledges the strength of each of the actors, it hampers a smooth transition from ideas to products for testing and from testing to market launch. The players within the R&D chain need to be better integrated to accelerate the development and delivery of an AIDS vaccine.

Where this is already achieved is in public-private partnerships for product development (PDPs). These organizations play an important role in closing the gaps in the R&D chain globally, and bring together resources from the public sector with expertise from biotech and pharmaceutical companies. They focus especially on poverty-related and neglected diseases, where private sector investments often fall short. The International AIDS Vaccine Initiative, one of the first PDPs, and the only one dedicated solely to developing an AIDS vaccine, can provide resources, manpower and access to valuable global networks to accelerate the R&D process. Most importantly, it provides a strong connection to the countries where an AIDS vaccine is most needed, especially Sub-Saharan Africa.

Another way to address the gap in the R&D chain is to incentivize the participation of the biotech sector; a sector with significant innovation power. Engaging in AIDS vaccine development is not an enticing prospect for most companies in this sector, given the complexity of the science and the overall lack of interest in the pharmaceutical sector to developing these vaccines. Yet, the engagement of the biotech sector will promote much needed translational research, turning scientific ideas into vaccine concepts that can be tested in clinical trials. Linking public research laboratories and biotech firms can mobilize the biotech involvement in AIDS vaccine R&D, so long as the industry contribution is adequately funded and collaborations involve relatively small numbers of partners.

Relevant facts and figures

Epidemiology

• Today, 33 million people are living with HIV/AIDS and almost 7500 people are newly infected every day.
• For every 2 persons starting on antiretroviral therapy, another 5 people become newly infected with HIV

Investment

• UNAIDS projected in September 2007 that the pricetag of universal access to AIDS prevention, treatment and care would be roughly $54 billion a year by 2015 (note: since then, UNAIDS revised its global epidemiological figure downwards (from 39 to 33 million people living with HIV/AIDS). However, at best, this will result in a cost reduction of 20%)
• The total spending on AIDS vaccine R&D globally was an estimated 961 million USD in 2007. The vast majority of this (82%; 789 million USD) came from the public sector. European funders increased their commitment to AIDS vaccine R&D in 2007 to US$80 million, up from $23 million in 2000. Still, total spending of European funders represents less than 10% of global spending on AIDS vaccine R&D (with the US contributing more than 80%).
• Only 10% of worldwide expenditure on health research and development is devoted to the problems that primarily affect the poorest 90% of the world's population; know as the “10/90” gap (figures from the Commission on Health Research for Development)

Timelines

• HIV was discovered in 1983; in the spring of 1984, 25 years ago, the discovery of HIV was publicly announced by the then US Health and Human Service Secretary Margaret Heckler, who predicted that a vaccine against HIV would be ready for testing within 2 years.
• It took scientists 47 years to develop a vaccine for polio and 42 years to find one for chicken pox

AIDS vaccine field

• Since the start of AIDS vaccine research, some 25 years ago, only 2 AIDS vaccines have been tested for their ability to protect against HIV infection (i.e. testing in clinical efficacy trials). The first was a gp120 vaccine candidate from Vaxgen; the second was the recent adeno-5 vaccine candidate from Merck.
• Today, there is one AIDS vaccine candidate in an efficacy trial, being tested for its ability to protect against HIV infection: a phase III trial in Thailand testing a canarypox vaccine candidate from Sanofi-Pasteur in combination (prime-boost) with the gp120 vaccine candidate from Vaxgen. Data from this trial are anticipated in 2009.
• Around 30 AIDS vaccine clinical trials are ongoing around the world, in which around 20,000 volunteers participate. Nearly all vaccine candidates in clinical development are based on the same concept, that of cell-mediated immunity. Today, there are no vaccine candidates in clinical trials that are able to elicit broadly neutralizing antibodies.
• Recent modeling conducted by IAVI shows a vaccine that is 50% effective (it is important to note that no existing vaccine is 100% effective) used in just 30% of the population would avoid 17 million new infections during the first 15 years following its introduction.

Source: IAVI - International Aids Vaccine Initiative