Bone marrow transplants offer a way to cure leukemia, sickle cell disease, and a variety of other life-threatening blood disorders.There are two major problems, however: One is many patients don’t have a well-matched donor to provide the marrow needed to reconstitute their blood with healthy cells. Another is even with a well-matched donor, rejection or graft versus host disease can occur, and lifelong immunosuppression may be needed.
A much more powerful option would be to develop a means for every patient to serve as their own bone marrow donor. To address this challenge, researchers have been trying to develop reliable, lab-based methods for making the vital, blood-producing component of bone marrow: hematopoietic stem cells (HSCs).
Two new studies by NIH-funded research teams bring us closer to achieving this feat. In the first study, researchers developed a biochemical “recipe” to produce HSC-like cells from human induced pluripotent stem cells (iPSCs), which were derived from mature skin cells. In the second, researchers employed another approach to convert mature mouse endothelial cells, which line the inside of blood vessels, directly into self-renewing HSCs. When these HSCs were transplanted into mice, they fully reconstituted the animals’ blood systems with healthy red and white blood cells.
Tags: adult stem cell therapy, adult stem cells, B cells, blood, blood cells, blood disorders, blood stem cells, bone marrow transplant, bone marrow transplantation, cell reprogramming, endothelial cells, graft versus host disease, hematopoietic stem cells, HSC, HSCs, immune system, immunosuppression, induced Pluripotent Stem cells, iPS cells, iPSCs, leukemia, red blood cells, regenerative medicine, sickle cell disease, stem cells, T cells, transcription factors, white blood cells
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 . 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.
Tags: AIDS, AIDS vaccine, antibodies, B cells, bnAbs, broadly neutralizing antibodies, eOD-GT8, eOD-GT8 60mer, HIV, HIV envelope, HIV vaccine, human immunodeficiency virus, immune system, immunology, infectious disease, nanoparticle, Phase I clinical trial, protein engineering, protein modeling, retrovirus, vaccine, virology
When most of us come down with a bacterial infection, we generally bounce back with appropriate treatment in a matter of days. But that’s often not the case for people who suffer from common variable immunodeficiency (CVID), a group of rare disorders that increase the risk of life-threatening bacterial infections of the lungs, sinuses, and intestines. CVID symptoms typically arise in adulthood and often take many years to diagnose and treat, in part because its exact molecular causes are unknown in most individuals.
Now, by combining the latest in genomic technology with some good, old-fashioned medical detective work, NIH-funded researchers have pinpointed the genetic mutation responsible for an inherited subtype of CVID characterized by the loss of immune cells essential to the normal production of antibodies . This discovery, reported recently in The New England Journal of Medicine, makes it possible at long last to provide a definitive diagnosis for people with this CVID subtype, paving the way for them to receive more precise medical treatment and care. More broadly, the new study demonstrates the power of precision medicine approaches to help the estimated 25 to 30 million Americans who live with rare diseases .
Tags: B cells, common variable immunodeficiency, CVID, exome, gamma globulin, genetic counseling, genomics, IKAROS, IKAROS deficiency, immunology, passive immunity, precision medicine, primary immune deficiency, rare disease, transcription factor
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 , 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.
Tags: AIDS, antibodies, B cells, bnAbs, broadly neutralizing antibodies, eOD-GT8 60mer, HIV, HIV envelope, HIV infection, HIV vaccine, immune response, immune system, nanoparticle, protein engineering, vaccines, virus