Beating the AIDS virus

Beating the AIDS virus


In The Lab: A microscopic image of a secondary AIDS infection. Getty Images

In what may bolster humanity’s chances of winning over the smart and clever human immunodeficiency virus (HIV), researchers have discovered two powerful antibodies which may become an Achilles heel for the dreaded virus. Scientists will now try to exploit HIV’s newfound vulnerability to craft novel approaches to design a more potent AIDS vaccine. “The findings are exciting. We’ve got a new, potentially better target on HIV to focus our vaccine design efforts,” said Wayne Koff, senior vice president of research and development at the International AIDS Vaccine Initiative (IAVI).

New bNAbs may help
The discovery of two broadly neutralising antibodies (bNAbs) may increase the chances of producing more such antibodies that in turn may reveal HIV’s additional vulnerabilities and give more vitality to the effort to develop an AIDS vaccine. Previous research conducted on primates showed neutralising antibodies prevented retrovirus infection in non-humans and can be a key for an effective HIV vaccine. Because HIV is a smart cookie that subtly changes its genetic make up when faced with survival threats, broadly neutralising antibodies are better suited to tackle the virus head on rather than those antibodies that can counter only specific HIV types. bNAbs are produced by a minority of HIV-infected individuals and distinct from other antibodies. Though conceptually it is better suited to protect against HIV, previous research with four similar antibodies did not yield much.

 “The four previously identified bNAbs are the subject of intensive investigation. However, these targets have been less accessible to immunogen design (vaccine development) than what we hope will be the case for the two new antibodies (PG 9 and PG16) based on the breadth and potency of these bNAbs,” Koff told Deccan Herald.

Why is the IAVI pinning such high hopes on these new candidates? “These new antibodies attach to a novel and potentially more accessible site on HIV,” said Dennis Burton, professor of immunology and microbial science at the Scripps Research Institute in La Jolla, California and scientific director of the IAVI.

 The antibodies target a region of the virus’s surface protein required to infect cells. For invading a cell, the virus uses two glycol-proteins, termed gp120 and gp41, which have evolved to thwart immune attack. That’s why those four were proven difficult to exploit in designing a vaccine. On the contrary, PG9 and PG16 target regions of gp120, unable to change in the face of a vaccine attack. They expose the virus’ vulnerability and select themselves as better leads to develop a vaccine by offering “breadth of neutralisation.”

Breadth of neutralisation is important because any effective AIDS vaccine must provide protection from a diverse range of prevalent types of HIV circulating globally. PG9 and PG16 are the first bNAbs to have been identified in more than a decade and are the first to have been isolated from donors in developing countries where the majority of new HIV infections occur.

Reporting their findings in the journal Science, scientists from Scripps Research Institute, California and two biotech companies, Theraclone Sciences and Monogram Biosciences said that they looked for bNAbs rather than the regular ones because of the variable nature of the virus.

The effort is distinguished by its emphasis on identifying antibodies that neutralize subtypes of HIV circulating primarily in developing countries. More than 1800 blood samples were collected from seven sub-Saharan countries and Thailand, Australia, the United Kingdom and the United States to find out these antibodies.

Repository stocks of various HIV subtypes kept at different institutes were utilised for testing the efficacy of the bNAbs. They were also found effective against sub type C, the commonest HIV strain found in India. “The two new bNAbs have neutralised a wide spectrum of subtype C viruses, including some HIV isolates from India. So, yes they would be expected to neutralize a broad spectrum though not 100 per cent of isolates circulating in India,” Koff said.  Two new technologies were used to identify the bNAbs.

 One was a micro-neutralization assay developed by biotech company Monogram and the second one is a high-throughput process to carry out huge numbers of screening tests at the same time and get results faster. Another biotech firm Theraclone developed that.

“If you think of it as a fishing expedition, we were previously using the wrong bait. We reasoned that the best approach to identifying antibodies with the most potent and broad neutralizing activity was to screen directly for their ability to block HIV infection. Our assay has opened up new avenues for exploration,” said Christos Petropoulos, chief scientific officer at Monogram Biosciences.

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