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Scientists discover how common vaccine booster works
May 22, 2008In an online paper in the journal Nature, Yale University researchers funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, explain how a common ingredient in many vaccines stimulates and interacts with the immune system to help provide protection against infectious diseases.
Vaccines must possess not only the bacterial or viral components that serve as targets of protective immune responses, but also ingredients to kick start those immune responses. In many vaccines, the bacterial or viral components themselves have this capability. For other vaccines, the immune system requires an added boost. Adjuvants are those substances added to a vaccine to help stimulate the immune system and make the vaccine more effective.
Currently the only vaccine adjuvants licensed for general use in the United States are aluminum hydroxide/phosphate formulations, known as alum. Although alum has been used to boost the immune responses to vaccines for decades, no one has known how it worked.
In this paper, the Yale team, led by Richard Flavell, M.D., Ph.D., and Stephanie Eisenbarth, M.D., Ph.D., examined the immune system pathway and cell receptors used by alum. Many microbial compounds function as adjuvants by stimulating Toll-like receptors. These receptors identify microbial invaders and alert the body to the presence of a disease-causing agent, or pathogen. Alum, however, does not stimulate Toll-like receptors. The Yale team found that alum stimulates clusters of proteins called inflammasomes, found inside certain cells. Inflammasomes respond to stresses such as infection or injury by releasing immune cell signaling proteins called cytokines. Inflammasomes are a component of the innate immune system that operates in parallel with, but separate from, Toll-like receptors, also part of the innate immune system.
To make this determination, Dr. Eisenbarth and her coworkers used mice that had been genetically engineered to be deficient in various components of a specific type of inflammasome, characterized by the presence of the protein termed Nalp3. The team demonstrated that an immune response did not occur in those animals with the deficient Nalp3 inflammasomes, despite the inclusion of alum, while it did occur in normal mice. The team's findings provide the first convincing evidence that the Nalp3 inflammasome forms the basis for alum's adjuvant action.
According to the study authors, several unanswered questions remain regarding how activation of this pathway controls a highly specific and long-lasting immune response generated by a vaccine. But this new information on the molecules that alum uses to activate the innate immune system should provide the keys to better understanding adjuvant function and should facilitate the design of new vaccine adjuvants.
NIH/National Institute of Allergy and Infectious Diseases
In this paper, the Yale team, led by Richard Flavell, M.D., Ph.D., and Stephanie Eisenbarth, M.D., Ph.D., examined the immune system pathway and cell receptors used by alum. Many microbial compounds function as adjuvants by stimulating Toll-like receptors. These receptors identify microbial invaders and alert the body to the presence of a disease-causing agent, or pathogen. Alum, however, does not stimulate Toll-like receptors. The Yale team found that alum stimulates clusters of proteins called inflammasomes, found inside certain cells. Inflammasomes respond to stresses such as infection or injury by releasing immune cell signaling proteins called cytokines. Inflammasomes are a component of the innate immune system that operates in parallel with, but separate from, Toll-like receptors, also part of the innate immune system.
To make this determination, Dr. Eisenbarth and her coworkers used mice that had been genetically engineered to be deficient in various components of a specific type of inflammasome, characterized by the presence of the protein termed Nalp3. The team demonstrated that an immune response did not occur in those animals with the deficient Nalp3 inflammasomes, despite the inclusion of alum, while it did occur in normal mice. The team's findings provide the first convincing evidence that the Nalp3 inflammasome forms the basis for alum's adjuvant action.
According to the study authors, several unanswered questions remain regarding how activation of this pathway controls a highly specific and long-lasting immune response generated by a vaccine. But this new information on the molecules that alum uses to activate the innate immune system should provide the keys to better understanding adjuvant function and should facilitate the design of new vaccine adjuvants.
NIH/National Institute of Allergy and Infectious Diseases
Immune System Current Events and Immune System News RSSMultiple health concerns surface as winter, vitamin D deficiences arrive
A string of recent discoveries about the multiple health benefits of vitamin D has renewed interest in this multi-purpose nutrient, increased awareness of the huge numbers of people who are deficient in it, spurred research and even led to an appreciation of it as "nature's antibiotic."
Factors from common human bacteria may trigger multiple sclerosis
Current research suggests that a common oral bacterium may exacerbate autoimmune disease. The related report by Nichols et al, "Unique Lipids from a Common Human Bacterium Represent a New Class of TLR2 Ligands Capable of Enhancing Autoimmunity," appears in the December 2009 issue of The American Journal of Pathology.
Surface bacteria maintain skin's healthy balance
On the skin's surface, bacteria are abundant, diverse and constant, but inflammation is undesirable. Research at the University of California, San Diego School of Medicine now shows that the normal bacteria living on the skin surface trigger a pathway that prevents excessive inflammation after injury.
Gene mismatch influences success of bone marrow transplants
A commonly inherited gene deletion can increase the likelihood of immune complications following bone marrow transplantation, an international team of researchers reports in the November 22 advance online issue of Nature Genetics.
Measuring and modeling blood flow in malaria
When people have malaria, they are infected with Plasmodium parasites, which enter the body from the saliva of a mosquito, infect cells in the liver, and then spread to red blood cells.
New cancer target for non-Hodgkin's lymphoma
Physician-scientists from Weill Cornell Medical College have discovered a molecular mechanism that may prove to be a powerful target for the treatment of non-Hodgkin's lymphoma, a type of cancer that affects lymphocytes, or white blood cells.
First reconstitution of an epidermis from human embryonic stem cells
Stem cell research is making great strides. This is yet again illustrated by a study carried out by the I-STEM* Institute (I-STEM/ Inserm UEVE U861/AFM), published in the Lancet on 21 November 2009. The I-STEM team, directed by Marc Peschanski has just succeeded in recreating a whole epidermis from human embryonic stem cells.
New findings suggest strategy to help generate HIV-neutralizing antibodies
New discoveries about anti-HIV antibodies may bring researchers a step closer to creating an effective HIV vaccine, according to a new paper co-authored by scientists at the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
UAB Researchers Discover Antibody Receptor Identity, Propose Renaming Immune-System Gene
Researchers at the University of Alabama at Birmingham (UAB) have uncovered the genetic identity of a cellular receptor for the immune system's first-response antibody, a discovery that sheds new light on infection control and immune disorders.
New culprit for viral infections among elderly -- an overactive immune response
Researchers at Yale School of Medicine have found that exaggerated responses of the immune system explain why the elderly succumb to viral infections more readily than younger people.
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