To fight HIV, the development of immunization strategies must keep up with how quickly the virus modifies itself. Now, Boston Children’s Hospital researchers are developing models to test HIV vaccines on a faster and broader scale than ever before with the support of the Bill & Melinda Gates Foundation.
The researchers are racing against HIV’s sophisticated attack on the human immune system. HIV, the human immunodeficiency virus, mutates much faster than other pathogens. Within each infected patient, one virus can multiply by the billions. …
An AIDS vaccine able to fight any HIV strain has thus far eluded science. HIV frequently mutates its coat protein, dodging vaccine makers’ efforts to elicit sufficiently broadly neutralizing antibodies.
“Only a small fraction of patients are able to develop broadly neutralizing antibodies, and by the time they do, the virus has already integrated into the genomes of their T-cells,” says Ming Tian, PhD, of Boston Children’s Hospital’s Program in Cellular and Molecular Medicine (PCMM).
Tian is part of a group led by PCCM director Frederick Alt, PhD, that developed a technology to greatly speed up HIV development. Described today in Cell, the group’s method generates mouse models with built-in human immune systems. The model recapitulates what the human immune system does, only much more rapidly, enabling researchers to continuously test and tweak potential HIV vaccines. …
Millions of people worldwide suffer from co-infection with tuberculosis (TB) and HIV. While prompt antibiotic and antiretroviral treatment can be a recipe for survival, over the years, physicians have noticed something: two or three weeks after starting antiretrovirals, about 30 percent of co-infected patients get worse.
The reason: immune reconstitution inflammatory syndrome, or IRIS. Doctors think it represents a kind of immune rebound. As the antiretrovirals start to work, and the patient’s immune system begins to recover from HIV, it notices TB’s presence and overreacts.
“It’s as though the immune system was blanketed and then unleashed,” says Luke Jasenosky, PhD, a postdoctoral fellow with Anne Goldfeld, MD, of Boston Children’s Hospital’s Program in Cellular and Molecular Medicine. “It then says, ‘I can start to see things again, and there are a lot of bacteria in here.'”
Though potentially severe, even fatal, IRIS may actually be a good sign: there is evidence that patients who develop it tend to fare better in the long run. But why does it arise only in some patients? …
The immune system, despite its immense complexity, really has only a few ways to kill bacteria:
Neutrophils and macrophages can capture and digest extracellular bacteria (ones that live free in tissues and the bloodstream).
Peptides (protein fragments) can punch holes in bacterial membranes or cross the membranes to disrupt bacterial processes.
T-cells can kill cells infected by intracellular bacteria (ones that take up residence within cells).
It’s this last mechanism that I want you to pay attention to. The conventional wisdom has long held that T-cells can only kill intracellular bacteria indirectly by eliminating the cells they’ve infected. But a paper by Judy Lieberman, MD, PhD, of Boston Children’s Hospital’s Program in Cellular and Molecular Medicine, reveals that T-cells have a hitherto unnoticed way of directly killing intracellular bacteria And she only found it because of HIV/AIDS. …
AIDS and HIV have been with us for more than 30 years. In that time, millions have died and millions more have been able to keep the virus at bay with a cocktail of medications called highly active antiretroviral therapy, or HAART.
But of those millions, only one person has reportedly been cured. As of this week, that number may now be two.
The key, according to their report, was aggressive and near immediate HAART treatment, starting before the child was 30 hours old and continuing until she was a year and a half old.
“This finding is hopeful but requires further study,” says Sandra Burchett, MD, MSc, clinical director of our Division of Infectious Diseases and director of the Children’s Hospital AIDS Program. “We all agree that treating babies infected with HIV as soon as possible maintains a healthy immune system; what we do not know is when, if ever, it is safe to stop HAART. Treating adults early after infection is not curative, but it may be that babies are somehow different.
“It is critically important, though,” she cautions, “for children, youth and young adults with HIV who are on HAART now to keep taking their medications, not stop on their own to see if they too are cured.”
Some question, though, whether the child was ever actually infected. Her doctors started therapy so early because her mother had uncontrolled HIV, putting the child at extremely high risk of developing the infection herself.
The only other patient reportedly ever cured of HIV is a man named Timothy Ray Brown. In 2006, Brown received a bone marrow transplant for leukemia, but with a twist: the marrow donor had been chosen for harboring a rare genetic mutation that conferred resistance to HIV. According to a paper published in the New England Journal of Medicine in 2009, Brown has been off HAART treatment since 2007 with little to no sign of infection.
Want to learn more? Click here to read an online Q&A with Burchett hosted by The Guardian on March 5.
Some 90 percent of us are exposed to the Epstein-Barr virus (EBV) at some point in our lives. While the immune system’s T cells rapidly clear most EBV-infected B cells, about one in a million infected cells escapes destruction. Within these cells, the virus enters a latent phase, kept in check by the watchful eye of so-called memory T cells.
This uneasy relationship usually holds steady for the rest of our lives, unless something suppresses the immune system – such as infection with HIV or use of anti-rejection drugs after a transplant – and breaks the surveillance. The virus can then reawaken and drive the development of certain B cell cancers.
This month marks an anniversary that no one wants to see: 30 years since the first paper describing what we know now as HIV/AIDS.
Over those three decades, more than 30 million people worldwide have died from the disease. We have learned a great deal – how HIV is passed from person to person, how long it circulated among humans before it was recognized, how to control it with antiretroviral drugs. Yet HIV still spreads: An additional 2.6 million people were infected with it in 2009 alone. Safe sex practices like condom use provide an effective barrier against passage of the virus, but don’t affect HIV’s ability to gain a foothold should the barrier fail.
Judy Lieberman and Lee Adam Wheeler want to move prevention beyond one-time physical blockades to longer-lasting, more reliable molecular resistance. “The current model of HIV transmission holds that the virus is localized to the genital tract for about a week,” says Lieberman, “which could provide a window of opportunity to intervene and prevent the infection from establishing itself throughout the body.” …
The number of mobile phone subscriptions worldwide is approaching 5 billion, many of them in developing countries where cell phones are the most reliable communications platform. So it’s no wonder that they’re becoming a global health tool to combat diseases like tuberculosis and AIDS.
Imagine you’re a long-suffering biologist, and imagine that the problem is figuring out the three-dimensional shape of a very important molecule. The solution could lead to (a) new insights into disease and potential therapies, and (b) career advancement. What if someone gave you virtually unlimited computer power that could crack the problem you’re trying to solve overnight?
A team at Children’s Hospital Boston has created a super-charged way of solving molecule shapes, harnessing idle scientific computer time across the country and around the world to survey vast reference databases – a “Google Shape” if you will.
HIV is unique among viruses in many ways. Here’s another: upon breaking into a cell, it erases evidence of its presence by exploiting a natural cellular “cleanup” mechanism. It thereby manages to dodge the innate immune system, the body’s first line of attack against invaders.