New antibody attacks 99% of HIV strains

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

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

The work is a collaboration between the US National Institutes of Health and the pharmaceutical company Sanofi.

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.

Super-antibodies

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 study, published in the journal Science, 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, told the BBC News website: "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," said Dr Nabel.

Experiments on 24 monkeys showed none of those given the tri-specific antibody developed an infection when they were later injected with the virus.

Dr Nabel said: "It was quite an impressive degree of protection."

The work included scientists at Harvard Medical School, The Scripps Research Institute, and the Massachusetts Institute of Technology.

'Exciting'

Clinical trials to test the antibody in people will start next year.

Prof Linda-Gail Bekker, the president of the International Aids Society, told the BBC: "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."

Source: https://www.bbc.com/news/health-41351159

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Gene-editing Approaches in Treatment of HIV-infected Non-human Primates

Gene editing of bone marrow stem cells in pigtail macaques infected with simian/human immunodeficiency virus (SHIV) significantly reduces the size of dormant "viral reservoirs" that pose a risk of reactivation. Christopher Peterson of the Fred Hutchinson Cancer Research Center in Seattle, WA, and colleagues present these findings in PLOS Pathogens.

In 2007, HIV-positive Timothy Brown, also known as the Berlin Patient, received a bone marrow stem cell transplant to treat his leukemia. The procedure eliminated HIV from his system, likely facilitated by a mutation in the gene CCR5 in the donor cells that made them resistant to HIV. However, it is rare to find matching donors with CCR5 mutations, and transplant is considered too dangerous for otherwise healthy HIV-positive patients, due to risk of donor cells attacking patients' cells.

To address this challenge, Peterson and colleagues are exploring the use of gene editing techniques to introduce the CCR5 mutation into a patient's own stem cells. In previous work, they demonstrated the ability to safely remove bone marrow stem cells from a healthy macaque, edit the CCR5 gene, and transplant the cells back into the macaque, where the CCR5-mutant cells successfully multiplied.

Now, the research team has performed the same technique in macaques infected with simian/human immunodeficiency virus (SHIV) and receiving antiretroviral therapy, making them analogous to HIV-infected people undergoing treatment to keep their HIV levels low. The scientists found that, after transplant, the CCR5 gene-edited cells were able to multiply in the macaques, giving rise to white blood cells that also had the mutation and were therefore resistant to SHIV.

Tissue analysis of the macaques detected edited cells in viral reservoirs -- collections of infected cells that have been hijacked by SHIV to produce more copies of the virus, but are currently in a dormant state. The edited cells appeared to reduce the size of these reservoirs, which is notable because viral reservoirs may reactivate to produce more SHIV at any time, and antiretroviral therapies have no effect on them.

Over time, about 4 percent of each macaque's white blood cells consisted of cells with the CCR5 edit -- too low a percentage to induce SHIV remission without also continuing antiretroviral therapy. The research team is now working to increase the efficiency of their gene-editing technique in order to raise this percentage. With better efficiency and in combination with other strategies, gene editing could one day help fight HIV in people.

Source: https://www.sciencedaily.com/releases/2018/04/180419141503.htm
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Early ART treatment tied to HIV remission

The research on early antiretroviral therapy has led to the fact that treatment of the virus during infancy may suppress HIV to undetectable levels which could reduce the need for life-long drug therapy. In the study, before treatment, the child’s levels of HIV in the blood, or viral load, were very high. At around 9 weeks of age, the child started ART, which suppressed the virus to undetectable levels. The child’s treatment was halted at 40 weeks, and their immune health was monitored during years of follow-up examinations.

Investigators assessed the child’s immune health and the presence of HIV at age 9.5 years. They found a reservoir of virus in a tiny portion of immune cells, but otherwise no evidence of HIV infection was detected and there were no associated symptoms.

While the researchers detected a trace of response by the immune system, they were unable to identify any HIV capable of replicating. It was confirmed that the child does not have genetic characteristics connected with spontaneous HIV control, which suggests that the 40 weeks of ART received during infancy may have played a key role in achieving HIV remission.

Since the initial treatment, the child has maintained undetectable levels of HIV. “To our knowledge, this is the first reported case of sustained control of HIV in a child enrolled in a randomized trial of ART interruption following treatment early in infancy,” says Dr. Avy Violari, head of pediatric research at the Perinatal HIV Research Unit at the University of the Witwatersrand in Johannesburg, South Africa, co-led the study with Mark Cotton, head of the Division of Pediatric Infectious Diseases at Stellenbosch University, also in South Africa.

Source: https://www.medicalnewstoday.com/articles/318636.php