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AIDS Vaccine Research: Better By Design?

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OD-GT8 60mer

Caption: eOD-GT8 60mer nanoparticle based on the engineered protein eOD-GT8. Yellow shows where eOD-GT8 binds antibodies; white is the protein surface outside the binding site; light blue indicates the sugars attached to the protein; dark blue is the nanoparticle core to which eOD-GT8 has been fused.
Credit: Sergey Menis and William Schief, The Scripps Research Institute

A while ago, I highlighted a promising new approach for designing a vaccine against the human immunodeficiency virus (HIV), the cause of AIDS. This strategy would “take the immune system to school” and teach it a series of lessons using several vaccine injections—each consisting of a different HIV proteins designed to push the immune system, step by step, toward the production of protective antibodies capable of fending off virtually all HIV strains. But a big unanswered question was whether most people actually possess the specific type of precursor immune cells that that can be taught to produce antibodies that kill HIV.

Now, we may have the answer [1]. In a study published in the journal Science, a research team, partly supported by NIH, found that the majority of people do indeed have these precursor cells. While the total number of these cells in each person may be low, this may be all that’s needed for the immune system to recognize a vaccine. Based in part on these findings, researchers plan to launch a Phase 1 clinical trial in human volunteers to see if their latest engineered protein can find these precursor cells and begin coaxing them through the complicated process of producing protective antibodies.


Toward an AIDS-Free Generation: Can Antibodies Help?

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Virus and antibody bound to virus

Caption: Left: Human Immunodeficiency Virus (HIV); Right: VRC01 antibody (blue and green) binding to HIV (grey and red). The VRC01-HIV binding (red) takes place where the virus attaches to primary immune cells.
Credits: C. Bickel, Science Translational Medicine; National Institute of Allergy and Infectious Diseases

This year, an estimated 50,000 Americans will learn they have been newly infected with the human immunodeficiency virus (HIV), which causes AIDS [1]. The good news is that if these people are diagnosed and receive antiretroviral therapy (ART) promptly, most will enjoy a near-normal lifespan.The bad news is that, barring any further research advances, they will have to take ART every day for the rest of their lives, a regimen that’s inconvenient and may cause unpleasant side effects. Clearly, a new generation of safe, effective, and longer-lasting treatments to keep HIV in check is very much needed.

That’s why I’m encouraged to see some early signs of progress emerging from a small, NIH-supported clinical trial of an HIV-neutralizing antibody. While the results need to be replicated in much larger studies, researchers discovered that a single infusion of the antibody reduced levels of HIV in the bloodstreams of several HIV-infected individuals by more than 10-fold [2]. Furthermore, the study found that this antibody—known as a broadly neutralizing antibody (bNAb) for its ability to defend against a wide range of HIV strains—is well tolerated and remained in the participants’ bloodstreams for weeks.


Creative Minds: Teaming Math and Science for an HIV Cure

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Alison Hill

Alison Hill

You may have heard about young mathematicians who’ve helped to design cooler cars, smarter phones, and even more successful sports teams. But do you know about the young mathematician who is helping to find a cure for the estimated 35 million people worldwide infected with the human immunodeficiency virus (HIV)? If not, I’d like to introduce you to Alison Hill, a mathematical biologist at Harvard University, Cambridge, MA.

Recognized this year by Forbes Magazine’s 30 Under 30 as one of the most important young innovators in healthcare, Hill is teaming with clinicians to develop sophisticated mathematical tools to predict which experimental drugs might work to clear HIV from the body once and for all. While current treatments are able to reduce some patients’ HIV burden to very low or even undetectable levels, it is eradication of this viral reservoir that stands between such people living with a serious, but controllable chronic disease and actually being cured.


Vaccine Research: New Tactics for Tackling HIV

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HIV-infected Immune Cell

Caption: Scanning electron micrograph of an HIV-infected immune cell.
Credit: National Institute of Allergy and Infectious Diseases, NIH

For many of the viruses that make people sick—think measles, smallpox, or polio—vaccines that deliver weakened or killed virus encourage the immune system to produce antibodies that afford near complete protection in the event of an exposure. But that simple and straightforward approach doesn’t work in the case of human immunodeficiency virus (HIV), the virus that causes AIDS. In part, that’s because our immune system is poorly equipped to recognize HIV and mount an attack against the infection. To make matters worse, HIV has a habit of quickly mutating as it multiplies.That means, in order for an HIV vaccine to be effective, it must induce antibodies capable of fighting against a wide range of HIV strains. For all these reasons, the three decades of effort to develop an HIV vaccine have turned out to be enormously challenging and frustrating.

But now I’m pleased to report that NIH-funded scientists have taken some encouraging strides down this path. In two papers published in Science [1, 2] and one in Cell [3], researchers presented results of animal studies that support what most vaccine experts have come to suspect: the immune system is in fact capable of producing the kind of antibodies that should be protective against HIV, but it takes more than one step to get there. In effect, a successful vaccine strategy has to “take the immune system to school,” and it requires more than one lesson to pass the final exam. Specifically, what’s needed seems to be a series of shots—each consisting of a different engineered protein designed to push the immune system, step by step, toward the production of protective antibodies that will work against virtually all HIV strains.


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