Scripps-led consortium scores $129M NIH grant to work on vaccine for stubborn HIV
Scientific effort into developing a vaccine against the HIV has proved elusive, as the virus rapidly mutates and its outer spike protein operates as an invisibility cloak, allowing it to outwit the immune system’s defensive arsenal. On Wednesday, a consortium of scientists led by Scripps Research unveiled a $129 million grant from the National Institutes of Health (NIH) that will help shepherd vaccines — engineered to combat a plethora of HIV strains — into the clinic.
HIV was once a death sentence, but is now considered a chronic illness. For those already afflicted, antiretroviral therapy must be taken every single day to suppress the virus or unbridled replication can overwhelm the immune system and eventually cause AIDS. Daily pills also rack up expensive bills in the United States, with monthly expenditure on treatment hitting thousands per month — depending on the regimen, insurance provider and rebates/discounts. Then there’s preventative treatment or PrEP (pre-exposure prophylaxis), in which individuals at high risk for HIV (typically men who have sex with men) take medicines daily to lower their chances of contracting the infection. According to the CDC, daily PrEP reduces the risk of getting HIV via sexual intercourse by more than 90%.
Still, there are nearly 37 million people living with HIV/AIDS globally, according to World Health Organization figures from 2017, a year which also saw 940,000 patients succumb to the disease. According to Scripps, despite existing prevention measures, globally 1.8 million people acquired HIV in 2017 (about one person every 15 seconds).
A key challenge researchers face is that one HIV-afflicted person can carry hundreds of thousands of variants of the virus at any given point. Scripps’ scientist Dennis Burton and his colleagues initiated their quest in 2009 when they discovered two potent antibodies in the blood cells of a woman living with HIV that appeared capable of neutralizing 70% of 162 HIV reference strains representative of the global epidemic.
Taking a cue from this finding, Burton et al. identified stable regions on HIV’s outer coat that could be targeted by bnAbs to develop immunogens. These molecules in animal studies demonstrated the ability to confer long-lasting protection against exposure to multiple HIV strains. This work was supported by a $77 million NIH grant which ran out this June.
This new capital injection will be used to refine the immunogens, develop scalable manufacturing apparatuses, and test the immunogens in early-stage human clinical trials. In partnership with the International AIDS Vaccine Initiative, the consortium of researchers are set to launch their first human clinical trial this year, Scripps said.
The promise of an HIV vaccine first became apparent in 2009, when a trial in Thailand tested a combination of two vaccines. In the trial, one vaccine was given in four doses and then “boosted” by two doses containing both vaccines. The analysis showed the group receiving the vaccine(s) had an infection rate 31.2% lower than the group that received the placebo — while this data was not compelling enough to make the cut for approval, the lessons of this trial are now being used for a variety of other efforts.
Last year, a study published in the Lancet journal from a similarly structured study offered encouraging results. Researchers from NIH, Harvard, J&J $JNJ and elsewhere used the same process of dosing a vaccine and then followed up the initial administration with ‘booster’ doses in non-infected patients at low risk of HIV. Data showed the vaccine regimens were well tolerated and induced robust immune responses in healthy individuals — they are now being tested in sub-Saharan Africa.
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