Fighting a smart virus


Fighting a smart virus

Research on AIDS vaccines is over a decade old. Why are there so few successes?

Scientific advances are often incremental and vaccine development in particular has typically been a decades-long affair. The polio vaccine was developed 47 years after the virus was identified. The vaccine has had several successes over the past year alone, including among other things, the first demonstration in humans that an AIDS vaccine can in fact prevent HIV infection and the discovery of new antibodies that potently neutralise a broad range of HIV variants—and whose characterisation has revealed new vulnerabilities on the virus for vaccine designers to target.

The HIV virus is smart. But how can a tiny virus become so smart as to fox scores of scientists worldwide?

It is quite simply the most elusive virus scientists have ever come across. There are several reasons for this. First, HIV is—far and away—the most mutable pathogen known to modern medicine, one that changes rapidly and constantly over the course of an infected person’s life. Every time the immune system of an infected person figures out how to target the virus, it simply mutates and avoids detection. Vaccine designers hoping to teach the body how to detect and destroy HIV are similarly challenged by its mutability.

Second, HIV very quickly inserts itself into the genetic makeup of human cells—hiding out in human DNA, far from the reach of the immune response, to sporadically re-emerge over the course of an infected person’s life. Third, the virus has evolved several other equally cunning mechanisms to evade neutralisation.

Finally, it attacks the very cells the immune system—and any vaccine—would need to marshal to clear the body of infection. Simply put, HIV is a formidable foe and will not be easily conquered. Still, scientists have developed vaccines against variable pathogens for which no ideal animal models exist—as is the case for HIV. A number of lines of evidence from both human and animal studies suggest that vaccines can be made to prevent HIV infection.

Why do we need vaccines in the first place because prevention programmes can bring down the prevalence of the disease and medicines are available to treat the infected persons?

Existing prevention programmes are valuable components to the AIDS crisis. Any vaccination campaign would complement but never entirely replace them. Still, these programmes have proved to be limited by their dependence on the willingness of people to modify their behaviour and make risk-reducing practices a habit. Condoms only work if used, and if partners agree to their use. Similarly, drugs are effective only if taken properly. They are also costly over the long term. Today, for every two people who receive life-saving anti-retroviral treatment, another five are newly infected with HIV.
A programme for addressing the HIV crisis that depends solely on behaviour modification and treatment isn’t likely to be sustainable. In fact, modelling done by IAVI suggests even with a full scale-up of all programmes for universal access to HIV treatment and prevention—a best case scenario—the number of new HIV infections would still hover around 1.5 million per year. An HIV vaccine, which neither generates resistance nor requires sustained compliance, would have a far-reaching impact on the pandemic.

Do you think that because of the hype associated with HIV/AIDS in late 1990s, IAVI was under pressure to deliver?

We put the pressure on ourselves. Our very existence is predicated on the belief that an AIDS vaccine cannot be developed fast enough but with the world notching up 7,500 new HIV infections every day, the need for such a vaccine is dire to say the least. We have done all we can to stress that while an AIDS vaccine is desperately needed, the development of one that is both safe and effective is going to be a long-term effort.

Is there a shortage in research funds for AIDS vaccines?

Yes, we do believe that too little money is earmarked for HIV vaccine research and new prevention tools generally. Support for AIDS vaccine development represents less than five per cent of the overall funding dedicated to AIDS treatment, prevention and care.
The field has recently had several breakthroughs in the search for a safe and effective AIDS vaccine, most notably the results of the RV144 efficacy trial in Thailand that demonstrated for the first time that HIV can be prevented by immunisation. I suspect funding declines have more to do with the global economic cycle than with any particular issue stemming from the science.

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