HIV ‘cured’ as South African child remains virus-free 8.5 years after final treatment
Injection prevents virus spreading, could rid sufferers of disease
Cow antibodies yield clues for developing effective AIDS vaccine
A South African child, believed to have been infected with Human Immuno-deficiency Virus (HIV) around the time of birth, has remained free of the virus for eight and half years after early treatment — renewing hope among scientists that such outliers may hold clues to help end the decades-old epidemic.
The case study, described by researchers before a presentation Monday at an international AIDS conference in Paris, France suggests a paradigm shift in the treatment of those infected. It establishes that HIV may be controllable in some way other than a daily and lifelong regimen of antiretroviral drugs.
“This is really the first step toward HIV remission and a cure,” said Deborah Persaud, a virologist at Johns Hopkins Children’s Center in Baltimore. “Understanding the factors that came into play to lead to this outcome is really going to inform science.”
Out of the millions of children worldwide who are HIV-positive, the child, now 9, is one of only three who have been identified by scientists as having the ability to stop the virus from resurging for an extended period of time.
Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, struck notes of both optimism and caution when speaking about him. Fauci described the child as being in “remission” rather than being cured. And while hoping that the child would never have an active infection, Fauci noted that HIV tends to hide in “funny places” and that it is “not entirely inconceivable” a small amount of the virus may remain in the body and start replicating again.
“It is exciting to see this. It is encouraging to see a child going for such a long period of time without rebounding,” Fauci said. “But we don’t have the full answers to what this means yet.”
The first case of extended remission in a child was announced to great excitement in 2013. Startled researchers reported that a girl — who came to be known as the Mississippi baby — appeared to be “functionally cured” 23 months after stopping treatment. The celebration was premature, however: The virus returned shortly after that announcement, and the young girl had to be put back on medications. But her case brought to light the possibility of viral suppression in children and led to the funding of other research into the phenomenon. The second case, reported in 2015, involved a French teen who underwent treatment from soon after birth to age six and whose blood continued to have undetectable levels of the virus for 12 years after stopping the drugs.
The South African child came to the attention of researchers in 2008 through a larger study funded by the National Institutes of Health. It took place from 2005 to 2011 at hospitals near Johannesburg and Cape Town and involved nearly 400 HIV-positive babies.
Also, an injection may soon be available that prevents the virus spreading and could rid sufferers of the infection, a study implies.
Researchers injected cows with HIV, all of which developed an immune response within as little as 35 days, a study found.
When the immune cells of the cows were analyzed, one in particular was found to bind to a key site on HIV that the virus uses to spread infection, the research adds.
The researchers believe such immune cells could be incorporated into an injection to neutralize HIV in infected humans.
Currently, there is no cure for HIV, with patients usually being required to take lifelong medication that causes nausea, diarrhea and insomnia. Researchers from multiple institutions, including Texas A&M University, injected HIV into the side of four calves.
Cows are not normally at risk of HIV, however, the researchers believe the animal’s immune system has specific features that allows it to produce antibodies when exposed to the virus.
As outlined in a study published in Nature, lead author Devin Sok, Director, Antibody Discovery and Development at the International AIDS Vaccine Initiative (IAVI), reports the elicitation of powerful, HIV-blocking antibodies in cows in a matter of weeks – a process that usually takes years in humans. The unexpected animal model is providing clues for important questions at a moment when new energy has infused HIV vaccine research.
“One approach to a preventive HIV vaccine involves trying to elicit broadly neutralizing antibodies in healthy people, but so far the experiments have been unsuccessful, in both human and animal studies,” said Sok, the study’s first author. “This experiment demonstrates that not only is it possible to produce these antibodies in animals, but we can do so reliably, quickly, and using a relatively simple immunization strategy when given in the right setting.”
Scientists have known for some time that some people living with chronic HIV infection produce broadly neutralizing antibodies (bnAbs), which can overcome the high levels of diversity of HIV. One type of bnAb, first reported in Science in 2009 by IAVI, The Scripps Research Institute (TSRI), and Theraclone, uses long, arm-like loops that are capable of reaching concealed areas on the virus’s surface to block infection. Previous experiments led by bovine-antibody expert Vaughn Smider at The Scripps Research Institute (TSRI) showed that cattle antibodies also feature extra-long loops, which might access difficult epitopes that human antibodies cannot. This feature is relevant for HIV researchers because the virus has a fence of sugars that it uses to prevent most antibodies from reaching its vulnerable sites.
Sok is an affiliate of IAVI’s Neutralizing Antibody Center (NAC), a part of TSRI where multiple groups of scientists work collectively on an antibody-based HIV vaccine. The NAC is led by scientific director Dennis Burton, Professor of Immunology and Microbiology at TSRI, who is a lead author on the study. Like a bull in a scientific china shop, an alliance of HIV, antibody, and veterinary medicine scientists from IAVI, TSRI and Texas A&M University posed the colorful question: what would happen if we immunized cows with an HIV immunogen?
“It’s a remarkably simple and profound idea,” said Sok, who works closely with Dennis Burton at TSRI. “Since we know that some human bnAbs have longer-than-average loops, would immunizing animals with similar antibody structure result in the elicitation of bnAbs against HIV?”
The answer begins with a single protein on HIV’s surface that serves as a bnAb target – develop an antibody that recognizes variants of this protein on different HIV viruses and you’ll likely be protected from all of them. One of the many tricks that HIV uses to prevent humans from developing the right antibodies is to display irrelevant forms of this protein to distract the immune system. Scientists thought they had overcome this challenge by developing an immunogen called BG505 SOSIP, which closely mimics the protein target. Immunization with this immunogen in macaques, guinea pigs, and rabbits was both encouraging and discouraging – it has elicited very good antibodies against one strain of the virus, but failed to elicit antibodies capable of overcoming HIV’s global diversity – until now.
All four cows immunized with BG505 SOSIP elicited bnAbs to HIV within 35-52 days. In comparison, it takes HIV-positive humans multiple years to develop comparable responses, and only 5-15% even develop them at all.
Cows cannot be infected with HIV, of course. But these findings illuminate a new goal for HIV vaccine researchers: by increasing the number of human antibodies with long loops, we might have an easier chance of eliciting protective bnAbs by vaccination.
There is no doubt that cows’ ability to produce bNAbs against a complicated pathogen like HIV in a matter of weeks, highlights even broader significance, particularly for emerging pathogens.
“Scientific innovations like this are what propel the field forward,” said IAVI CEO Mark Feinberg. “This surprising set of results warrants further exploration and has potential applications not only to HIV prevention and treatment, but to the rapid development of antibodies and vaccines against other infectious diseases.”
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