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HIV vaccine is a daunting challenge
It's been 30 years since the AIDS epidemic spread to every corner of the world killing nearly 30 million people, infecting more than 60 million. There is still no vaccine or cure for it. However, what we do know is that AIDS is preventable. Margaret (Margie) McGlynn, who retired from Merck in 2009, after 26 years with the company to head the International Aids Vaccine Initiative, was in India recently. She was in India to launch the HIV Vaccine Translational Research Laboratory established by India's department of biotechnology that will spearhead India's search for an AIDS vaccine. In an exclusive interview to TOI-Crest she talks about challenges of finding a vaccine for AIDS.
What is stopping scientists from finding a vaccine that works?
Developing an effective vaccine to prevent HIV infection is one of the most daunting challenges scientists have ever faced. HIV is an incredibly elusive virus, for many reasons. First of all, it attacks the very cells that the immune system would need to clear the body of infection. Further, it very quickly inserts itself into the genetic makeup of human cells, hiding out in human DNA, far from the reach of the immune response. And on top of that, the virus is highly mutable, changing its genetic material rapidly and constantly over the course of HIV infection. As a consequence, major variants of the virus that predominate in various regions of the world, known as clades, differ from each other significantly. This is why it is very difficult to develop a broadly effective vaccine.
Realistically, how early do you think the world can see a HIV vaccine that can be used?
Unfortunately, there is no way to predict when we will see an effective AIDS vaccine that is ready to be used by the general population. There is one vaccine candidate, known as HVTN 505, currently in an efficacy trial and the results are expected by early 2014. Another regimen of candidate vaccines has shown some measure of efficacy in such a trial. This efficacy trial conducted in Thailand - known as RV144 - established for the first time that vaccines can indeed provide protection from HIV. However, it will take a number of years to complete all of the planned follow-up trials of vaccines based on the RV144 candidates. There are also several nextgeneration candidates moving through the pipeline today. Many of these candidates are in the pre-clinical testing and a few in the Phase I testing stage. To date, there are more than 30 vaccine candidates in clinical trials.
What do you think of India's HIV vaccine research programme?
We are encouraged by India's growing participation in HIV vaccine research and development. IAVI has long considered the nation a major partner in vaccine development and design. We are also very happy to see that the governments of India and South Africa have launched a joint programme for AIDS vaccine research and development.
Is there a candidate vaccine from India that could work?
Not yet. So far, only one HIV vaccine candidate has demonstrated modest efficacy, and researchers are now working to improve upon those results. The only valid proof that any vaccine candidate has promise comes from large scale efficacy trials examining its ability to protect people from the disease.
Is there a funding shortage in HIV vaccine research?
The global financial crisis has put a strain on many global health R&D budgets. For AIDS vaccines, total funding dropped 2% from 2010 to 2011. This continues a downward trend in AIDS vaccine funding that began in 2008. According to the most recent report from the HIV Vaccines and Microbicides Resource Tracking Working Group, the 2011 total investment in HIV vaccines was $845 million, a decrease of $14 million from 2010.
There are funding challenges associated with the development of an AIDS vaccine, leading to flat or slightly decreased funding. At the same time, there are new discoveries that could benefit from increased funding. Some donors are discouraged that a vaccine has not yet been brought to market and are shifting their investments to other priorities. Also, the global economic crisis has diminished the resources available to donors to address global health priorities.
Do you think the world at large and donors in particular are losing interest in HIV?
Although there has been some general fatigue associated with addressing the AIDS pandemic, there is currently new found excitement in the field given the enormous strides on a variety of HIV prevention fronts in recent years. At the recent International AIDS Conference, global supporters, including Bill Gates, Tony Fauci and secretary Clinton, spoke with great conviction about the continued need for investment in HIV vaccine R&D. We are confident that, given the scale and severity of the HIV crisis, donors will continue to support efforts to develop new tools for HIV prevention.
For a vaccine to be effective, what does it have to do?
IAVI researchers and many other scientists in the field believe that an effective vaccine will have to accomplish two things. First, it will have to teach B cells of the so-called humoral immune response to detect HIV and generate antibodies against HIV that are capable of neutralising the virus. Though the immune system makes huge amounts of antibodies to HIV, most of those do not stop HIV from infecting its target cells, which are primarily CD4+ T cells. The trick is to devise a vaccine that can teach B cells to generate antibodies capable of blocking entry of the virus into CD4+ cells. But any truly effective vaccine will also likely have to provoke a powerful cellular immune response. Researchers also suspect that the efficacy of these responses might be improved if the vaccine in question induces them within the mucosal tissues that line inner body cavities, where sexually transmitted HIV typically initiates infection. A number of research organisations are designing vaccines candidates to address all of these needs.
How will an HIV vaccine help in reducing HIV numbers or reducing new infections?
IAVI partnered with an organisation known as the Futures Institute to develop a mathematical model that explores the potential impact of an HIV vaccine in countries most affected by HIV. In a scenario where current coverage trends in HIV treatment and prevention continue through 2030, the model shows that an AIDS vaccine introduced in 2020, even one that is only partially effective, could have a substantial impact on the AIDS pandemic in low- and middle-income countries and lead to a dramatic decline in the number of new infections. For example, a preventive AIDS vaccine of just 50% efficacy given to 30% of the population in low-and-middle income countries could avert almost 20% of all infections between 2020 and 2030 - that's 5. 2 million new infections avoided.
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