Grand Challenges offer opportunities for HIV research funding

This article is more than 16 years old.

The Bill and Melinda Gates Foundation has announced a grant of US $200 million to challenge the scientific community to address a global public health research agenda. This is defined as a series of 14 'Grand Challenges' with one aim being, to encourage researchers who have not traditionally been active in public health to work on these issues. There is a deliberate echo of occasions when mathematicians, for example, have defined the main outstanding problems in a field in ways that have then led to the development of many new techniques.

Grants of up to US $20 million each, over periods of up to 5 years, will be awarded to teams - which may be in the public, private or independent sector, anywhere in the world - whose proposals survive a peer-review process to be administered by the NIH Foundation, a research charity linked to the US National Institutes of Health. Along the way, NIH will seek to identify proposals to be funded by the US government, in addition to the funding made available by the Gates Foundation.

The application process will be two-stage, with initial 'letters of intent' due in January 2004 used as a basis for inviting applicants to submit detailed funding proposals. (Full details are available on the Grand Challenges website here.)

Glossary

strain

A variant characterised by a specific genotype.

 

malaria

A serious disease caused by a parasite that commonly infects a certain type of mosquito which feeds on humans. People who get malaria are typically very sick with high fevers, shaking chills, and flu-like illness. 

cure

To eliminate a disease or a condition in an individual, or to fully restore health. A cure for HIV infection is one of the ultimate long-term goals of research today. It refers to a strategy or strategies that would eliminate HIV from a person’s body, or permanently control the virus and render it unable to cause disease. A ‘sterilising’ cure would completely eliminate the virus. A ‘functional’ cure would suppress HIV viral load, keeping it below the level of detection without the use of ART. The virus would not be eliminated from the body but would be effectively controlled and prevented from causing any illness. 

hepatitis B virus (HBV)

The hepatitis B virus can be spread through sexual contact, sharing of contaminated needles and syringes, needlestick injuries and during childbirth. Hepatitis B infection may be either short-lived and rapidly cleared in less than six months by the immune system (acute infection) or lifelong (chronic). The infection can lead to serious illnesses such as cirrhosis and liver cancer. A vaccine is available to prevent the infection.

attenuated

Weakened. Attenuated viruses are often used as vaccines because they no longer cause disease but may still stimulate a strong immune response.

What may be of particular interest for the future of HIV research is that more than half of the 'Grand Challenges' are directly relevant to HIV treatment and prevention. HIV research is explicitly recognised as a priority - alongside TB, malaria, hepatitis B and C, and other communicable diseases.

So what are these 'Grand Challenges' and how do they relate to HIV?

The first three are concerned with childhood vaccine development. Specifically, to 'Create effective single-dose vaccines that can be used soon after birth', 'Prepare vaccines that do not require refrigeration' and 'Develop needle-free delivery systems for vaccines'. The potential re-use and difficulty in ensuring safe disposal of syringes create serious disease risks, including a risk of HBV, HCV and HIV transmission, in many settings. If the first could be solved, then it could ease the way towards using a future HIV vaccine to protect babies against breast milk transmission. The second, if solved, would do much to help secure access to new vaccines as well as existing ones.

The next group relate to the development of wholly new preventive vaccines, with HIV as a priority target.

'Devise reliable tests in model systems to evaluate live attenuated vaccines' is NOT about live attenuated HIV, currently ruled out on safety grounds. Instead, it is about finding ways to test new vaccines based, for example, on weakened strains of bacteria that can be given orally. It could also mean developing research strains of mice, rats or rabbits so that HIV vaccine research does not depend on monkeys.

'Solve how to design antigens for effective, protective immunity' highlights the challenge of creating vaccines that generate broadly protective antibodies against HIV. 'Learn which immunological responses provide protective immunity' is about finding better ways to assess vaccines in clinical trials.

Two challenges refer to chemical or genetic methods of controlling disease-carrying insect populations, such as mosquitos or tsetse flies, and one controversially refers to modifying food crops to enhance their micronutrient content to address continuing, widespread malnutrition. While it calls for proposals to 'Create a full range of optimal, bioavailable nutrients in a single staple plant species' the technique could then clearly be applied to a whole range of different crops, following the example of vitamin-enhanced rice.

The next three challenges all refer to communicable diseases and give HIV as a priority. 'Discover drugs and delivery systems that minimize the likelihood of drug resistant micro-organisms' includes the development of drugs against new targets, especially within the cell, which organisms such as HIV could not readily become resistant to. It also includes new ways to deliver drugs to reduce adherence problems.

'Create therapies that can cure latent infections' would be directed in the case of HIV against infected cells that allow the virus to survive in the body despite immune responses and drug treatment. It is equally important to develop better treatments for TB and other conditions that can similarly survive for years, only to become active when the immune system weakens.

'Create immunological methods that can cure chronic infections' is primarily about the use of vaccines as part of an approach to treatment - 'therapeutic vaccination'. This is closest to clinical use in the case of HPV strains which cause cervical cancer, but the Challenge mentions HIV, HBV, HCV, HSV and the parasite Schistosoma too.

The last two challenges are about ways to 'Measure disease and health status accurately and economically in developing countries', and specifically to 'Develop technologies that permit quantitative assessment of population health status' (with particular reference to improving health statistics for preventable causes of illness and death) and finally, to 'Develop technologies that allow assessment of individuals for multiple conditions or pathogens at point-of-care'.

Of all the 14 challenges, the final one may be the most likely to revolutionise the lives of people with HIV. Accurate and rapid diagnosis of opportunistic and sexually transmitted infections, low-cost, reliable and rapid CD4 counts and viral loads. Tests to identify drug-resistant strains of TB and HIV. Better methods to separate malaria from other fevers. Proper diagnosis of Pneumocystis pneumonia ... the list goes on.

While the immediate response to these challenges will be interesting to see, perhaps the biggest challenge of all will be to scientific priorities, the balance between pure and applied research, and in drawing attention to the global imbalance between public health needs and the effort put in - especially by private industry - to meeting them.