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New vaccine approach could turn HIV’s sugar coating into its Achilles’ heel

20 July 2010

The chains of sugar molecules, or carbohydrates, that cover the outside of the highly variable HIV virus remain constant, are different from those found on human cells, and could form the basis of a promising new approach to an AIDS vaccine, according to research led by the University of Oxford.

The researchers suggest that a vaccine based on synthetic versions of the HIV carbohydrate coat, because it is so unchanging, could prime the body’s immune system to recognise the otherwise rapidly changing HIV virus and fight off any infection.

We’re used to flu vaccines being reformulated every year because new strains come along,’ says Dr Chris Scanlan of the Department of Biochemistry at the University of Oxford, who led the research. ‘Yet you will see more viral diversity develop in a single HIV patient in a single day than you will in the whole flu season this year across the whole of the UK. That is some challenge for developing a vaccine against HIV.

‘We’re cautiously optimistic that this research could lead to a promising new approach for a vaccine against HIV/AIDS,’ says Dr Scanlan. ‘We’ve found something that doesn’t change across all classes of HIV – from viruses found in the USA to those in Uganda – and it’s something that can be made and manufactured.

The team from Oxford University, The Scripps Research Institute in La Jolla, California, and the Ragon Institute in Boston, Massachusetts report their findings in the journal Proceedings of the National Academy of Sciences.

The researchers were able to isolate the carbohydrate coating from different samples of live HIV-1 virus, representing typical viruses found in different parts of the world, and analyse their chemical structures for the first time. They found that the carbohydrates are unique and are found across all classes or ‘clades’ of HIV-1. Importantly, these carbohydrates are completely different to the patterns of sugars found on human cells.

The researchers also showed that existing vaccines being developed against HIV will not have the same carbohydrate structures within their formulations as the native HIV virus and so may not mimic this element of the virus adequately.

‘The dense cloud of carbohydrates covering the virus has been called its ‘carbohydrate camouflage’ because the carbohydrate chains look like those on the outside of the body’s own cells, and so they aren’t normally recognised by the immune system,’ explains Dr Scanlan.

‘We’ve shown that HIV’s camouflage may be flawed. The carbohydrates on an HIV virus are different to the body’s own cells, and that might give us an opportunity to attack.

‘It is possible to educate the immune system to these differences. You can include danger signals in your vaccine formulation to force the immune system to take notice of particular carbohydrate structures. Some cancer vaccines in development use this approach, for example,’ he adds.

The team now aim to come up with ways of making synthetic versions in the lab of the particular carbohydrates found on the outside of HIV. These could then be combined with an adjuvant – a factor that enhances the body’s immune response – to give a completely new vaccine candidate for evaluation.

The researchers have already shown in their PNAS paper that it is possible to modify a human cell line to produce the gp120 HIV protein with the correct carbohydrates attached. This is one way that the carbohydrates for any future vaccine could be produced.

For more information please contact Dr Chris Scanlan of the University of Oxford on +44 (0)1865 275340, +44 (0)7776 144850, or chris.scanlan@bioch.ox.ac.uk

Or the University of Oxford press office on +44 (0)1865 280530 or press.office@admin.ox.ac.uk 

Notes to Editors

  • According to the latest WHO estimates, 33.4 million people were living with HIV in 2008. That year, it is estimated that 2.7 million people will have become newly infected with HIV while 2 million will have died from AIDS. http://www.who.int/hiv/data/global_data/en/index.html
  • The Health Protection Agency’s 2009 report on HIV in the UK showed that the number of people living with HIV in the UK continues to rise, with an estimated 83,000 infected at the end of 2008, of whom over a quarter (27%) were unaware of their infection. http://www.hpa.org.uk/web/HPAweb&HPAwebStandard/HPAweb_C/1259151891866
  • The paper ‘Envelope glycans of immunodeficiency virions are almost entirely oligomannose antigens’ by Katie Doores and colleagues is to be published in the journal PNAS with an embargo of 20.00 UK time / 15.00 ET (USA) on Monday 19 July 2010.
  • The research was funded by the International AIDS Vaccine Initiative (IAVI), the Oxford Glycobiology Endowment, the National Institute of Allergy and Infectious Diseases, and the Ragon Institute.
  • Oxford University’s Medical Sciences Division is one of the largest biomedical research centres in Europe. It represents almost one-third of Oxford University’s income and expenditure, and two-thirds of its external research income. Oxford’s world-renowned global health programme is a leader in the fight against infectious diseases (such as malaria, HIV/AIDS, tuberculosis and avian flu) and other prevalent diseases (such as cancer, stroke, heart disease and diabetes). Key to its success is a long-standing network of dedicated Wellcome Trust-funded research units in Asia (Thailand, Laos and Vietnam) and Kenya, and work at the MRC Unit in The Gambia. Long-term studies of patients around the world are supported by basic science at Oxford and have led to many exciting developments, including potential vaccines for tuberculosis, malaria and HIV, which are in clinical trials.
  • The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations, at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel. Scripps Research is headquartered in La Jolla, California. It also includes Scripps Florida, whose researchers focus on basic biomedical science, drug discovery, and technology development. Scripps Florida is located in Jupiter, Florida.