Engineered antibody that attacks HIV strains an ‘exciting breakthrough’

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Scientists have engineered an antibody that attacks 99% of HIV strains and can prevent infection in primates, reports BBC News.

Scientists from Sanofi, the Vaccine Research Centre, National Institute of Allergy and Infectious Diseases, Bethesda, the Centre for Virology and Vaccine Research, Beth Israel Deaconess Medical Centre, Harvard Medical School, Boston, the Ragon Institute of MGH/MIT and Harvard, Cambridge and the department of immunology and microbiology, IAVI Neutralising Antibody Centre, Centre for HIV/AIDS Vaccine Immunology and Immunogen Discovery, and The Scripps Research Institute, La Jolla, California, were involved.

It is built to attack three critical parts of the virus – making it harder for HIV to resist its effects.

The International Aids Society said it was an “exciting breakthrough”. Human trials will start in 2018 to see if it can prevent or treat infection.

Our bodies struggle to fight HIV because of the virus’ incredible ability to mutate and change its appearance. These varieties of HIV – or strains – in a single patient are comparable to those of influenza during a worldwide flu season. So the immune system finds itself in a fight against an insurmountable number of strains of HIV.  But after years of infection, a small number of patients develop powerful weapons called “broadly neutralising antibodies” that attack something fundamental to HIV and can kill large swathes of HIV strains.

Researchers have been trying to use broadly neutralising antibodies as a way to treat HIV, or prevent infection in the first place.

The report says the study combines three such antibodies into an even more powerful “tri-specific antibody”. Dr Gary Nabel, the chief scientific officer at Sanofi and one of the report authors, is quoted in the report as saying: “They are more potent and have greater breadth than any single naturally occurring antibody that’s been discovered.” The best naturally occurring antibodies will target 90% of HIV strains. We’re getting 99% coverage, and getting coverage at very low concentrations of the antibody.”

Experiments on 24 monkeys showed none of those given the tri-specific antibody developed an infection when they were later injected with the virus. Nabel said: “It was quite an impressive degree of protection.” Clinical trials to test the antibody in people will start next year, the report said.

Professor Linda-Gail Bekker, the president of the International Aids Society, is quoted in the report as saying: “This paper reports an exciting breakthrough. These super-engineered antibodies seem to go beyond the natural and could have more applications than we have imagined to date. It’s early days yet, and as a scientist I look forward to seeing the first trials get off the ground in 2018. As a doctor in Africa, I feel the urgency to confirm these findings in humans as soon as possible.”

Dr Anthony Fauci, the director of the US National Institute of Allergy and Infectious Diseases, said it was an intriguing approach. He added: “Combinations of antibodies that each bind to a distinct site on HIV may best overcome the defences of the virus in the effort to achieve effective antibody-based treatment and prevention.”

Abstract
The development of an effective AIDS vaccine has been challenging due to viral genetic diversity and the difficulty in generating broadly neutralizing antibodies (bnAbs). Here, we engineered trispecific antibodies (Abs) that allow a single molecule to interact with three independent HIV-1 envelope determinants: 1) the CD4 binding site, 2) the membrane proximal external region (MPER) and 3) the V1V2 glycan site. Trispecific Abs exhibited higher potency and breadth than any previously described single bnAb, showed pharmacokinetics similar to human bnAbs, and conferred complete immunity against a mixture of SHIVs in non-human primates (NHP) in contrast to single bnAbs. Trispecific Abs thus constitute a platform to engage multiple therapeutic targets through a single protein, and could be applicable for diverse diseases, including infections, cancer and autoimmunity.

Authors
Ling Xu, Amarendra Pegu, Ercole Rao Nicole, Doria-Rose Jochen, Beninga Krisha McKee, Dana M Lord, Ronnie R Wei, Gejing Deng, Mark Louder, Stephen D Schmidt, Zachary Mankoff, Lan Wu, Mangaiarkarasi Asokan, Christian Beil, Christian Lange, Wulf Dirk Leuschner, Jochen Kruip, Rebecca Sendak, Young Do Kwon, Tongqing Zhou, Xuejun Chen, Robert T Bailer, Keyun Wang, Misook Choe, Lawrence J Tartaglia, Dan H Barouch, Sijy O’Dell, John-Paul Todd, Dennis R Burton, Mario Roederer, Mark Connors, Richard A Koup, Peter D Kwong, Zhi-yong Yang, John R Mascola, Gary J Nabel

BBC News report
Science abstract


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