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IAVI to begin clinical study on HIV elite controllers

THE progression of Human Immuno Virus (HIV) infection to a full blown Acquired Immune Deficiency Syndrome (AIDS) varies from one infected person to another. But few among the infected population, known as elite controllers, manage to keep their CD4 count low (a higher CD4 count means heavy viral load and such a person can infect another). This means, prolonging Anti Retroviral Therapy (ART), drugs required to keep the viral load low that need to be taken lifelong. What prevents the otherwise highly active HIV virus from reproducing in such individual’s body is a mystery. But certain recent studies have unravelled clues that have made scientists optimistic in solving this mystery.

This small group comprises less than three per cent of the HIV infected population and has certain additional antibodies in their immune system that hampers the virus from making copies of itself. Scientists see hope in this considering the virus keeps evolving and sheds some of its previous characteristics when it replicates.

A recent study carried out by International AIDS Vaccine Institute (IAVI), a non-profit organisation researching for AIDS vaccine, found that the elite controllers have certain neautralising antibodies, which attacks specific areas on the outer surface of the virus. Researchers believe that these portions are vulnerable areas of the virus. It is still unclear that this stage how many such antibodies exist, whether more than one antibody is present in a person or even whether there are other vulnerable sites on the virus. However, at least 17 neautralising antibodies have been identified in small group of elite controllers in a clinical study conducted in Africa.

Indian study

To corroborate the African study findings, a similar clinical trial will be conducted in India, early this year, the IAVI officials said. The study will have a small sample size of 100 HIV positive individuals, who have been infected for the last three years but have less than 50,000 copies of the virus; the elite controllers in the Indian setting. The screening and research on the samples will be carried out at Y R Gaitonde Centre for AIDS Research and Education (YRG CARE), Chennai, from where the samples will be sent to newly created Translational Health Sciences Technology Institute (THSTI), near Delhi. A joint collaboration between Department of Biotechnology, Government of India and IAVI, THSTI was set up to provide impetus to domestic research earlier last year. Trained by IAVI, the staff at THSTI will analyse the samples and match it with the African samples Considering India’s huge population, IAVI believes the study would throw up wider gamut of neutralising antibodies in elite controllers.

This hope come from the fact that as many as 17 new neautralising antibodies were discovered by researchers, which clustered in a different site – PG T – on the outer surface of the HIV virus, during the African study. While two neutralsing antibodies – PG 9 and PG 16 – were identified in 2009, which bound to a portion of the HIV virus’s outer protein cover that was vulnerable, the idea of the study was see whether there were other such vulnerable sites that other neutralising bodies attacked especially in this sub group. And indeed, after conducting series of tests on 18 elite controllers, four samples had 17 antibodies that targeted a different site on the virus. The structure of one of them was recently discovered by scientists at IAVI, said Dr Wayne Koff, Chief Scientific Officer and senior vice president, IAVI.

Around 2,000 HIV positive people were screened for the African study of which, only 200 had antibodies that matched the IAVI criteria. However, only 10 per cent or 18 individuals from this narrowed sample had variety of potent neautralising antibodies.

Dr Koff explained that a quarter of the elite controllers had made antibodies targeting CD 4 binding sties, another quarter had antibodies attacking PG 9 site and still another quarter struck at PG T site. ”Now we are screening more such number of sites,” he said. Besides this, the scientists have not found any person having antibodies that targeted all the three sites, which may turn up in the Indian study.

He explained that one of the approaches they were considering for vaccine development was to target the entire protein cover of the virus rather than any one site. So, engineer a vaccine that can attack all the three sides, revealed in the African study. In addition, it will stimulate varied and effective neutralising antibodies, which can eliminate the HIV virus at the entry level itself. If even one per cent of the virus gets in the T cells will be robust to attack it and knock it off at the mucosa (innermost layer of colon), Dr Koff said.

Domestic grants

Meanwhile, decline in research grants worldwide has forced countries invest inwards i.e. domestic research. And, India has taken a lead in this by creating THSTI, said IAVI country director Dr Rajat Goyal. Collaboration has become the buzz word, with researchers taking advantage of each other’s expertise and resources. This was clearly witness during the correlate research of Thai HIV vaccine candidate RV144, which saw collaboration from 35 investigators from 20 institutes worldwide.

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