Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Sepsis vaccine proves protective in preliminary studies at The Scripps Research Institute

13.11.2002


A group of researchers from The Scripps Research Institute (TSRI) have designed a vaccine that might be used to protect against the pernicious consequences of severe sepsis, an acute and often deadly disease that is estimated to strike 700,000 Americans a year and millions more worldwide.



Though the new vaccine has not yet been applied to clinical trials in humans, it has worked well in preclinical studies, the results of which the team reports in the latest issue of the journal Angewandte Chemie.

"The vaccine provided outstanding protection," says author Kim Janda, Ph.D., who holds the Ely R. Callaway, Jr. Chair in Chemistry at TSRI.


A Rapid and Deadly Disease

Sepsis, also known as septic shock and systemic inflammatory response syndrome, is characterized by shock to one’s organs following poisoning with endotoxins--chemical components of certain bacteria. The endotoxin molecules themselves are not particularly harmful, but the way that the immune system reacts to them is.

When bacteria like the deadly N. meningitidis invade the body, they trigger the immune system to stage a biochemical defense. One of the ways that the body initially responds to such an infection is to recruit white blood cells, like macrophages, which engulf the pathogens and destroy them. The macrophages also fight the pathogens by producing chemicals at the site of an infection that induce inflammation.

However, there is a limit to how much inflammation a body can take. If the infection is widespread, the systemic endotoxin levels can be so high that the macrophages respond by producing a lethal amount of inflammatory chemicals. One of these chemicals is called tumor necrosis factor alpha (TNF-alpha).

The prognosis for sepsis is dire. It can affect many parts of the body, from the bones to the brain, and death due to septic shock can occur in a matter of hours. According to the National Institutes of Health, two percent of all hospital admissions suffer from sepsis, and its typical case-fatality rate is around 30 percent. According to the Centers for Disease Control and Prevention, sepsis is one of the ten leading causes of both infant and adult mortality in the United States, and, in 1999, directly caused more than 30,000 deaths.

A New Approach

The best current treatment is to administer broad-spectrum antibiotics to try to quell the infection after the fact, but this is often too little too late and scientists have sought a better approach for years.

Since many patients who fall victim to sepsis acquire bacterial infections in the hospital, after undergoing major surgeries for instance, one approach would be to try to "prophylactically" protect a patient before he/she undergoes surgery.

Many scientists have sought to achieve such protection through passive immunization--by infusing antibodies into the patient to target the endotoxins. Many of the compounds that have been tested to date have proven to have limited effect, though, for reasons that are not entirely clear.

The TSRI team’s approach is fundamentally different. They sought to use active immunization to protect patients against sepsis. Active immunization, used in measles, smallpox and polio vaccines, involves exposing patients to a substance that resembles the pathogen that one is immunizing against.

If the vaccine works, the body responds with an effective immune response both to the vaccine and to the pathogens that are later encountered. In this case, the TSRI team designed a synthetic "glycoconjugate" that mimics one of the most common bacterial endotoxins, called "lipid A."

Post-vaccination, they observed a nearly 95 percent reduction in the inflammatory chemical TNF-alpha which indicated that the vaccine successfully controlled the body’s response to infection.

Significantly, the vaccine seems to raise a broad antibody response, possibly inducing the formation of antibodies that have some enzymatic ability and can "hydrolyze" or chop up the lipid A. Researchers designed the vaccine to raise such "catalytic" antibodies by making a portion of it resemble a form of lipid A. This two-pronged approach may be the reason why the vaccine proved particularly protective.

"Now that we have evidence that [the vaccine] provides good protection in a mouse model, we really want to go on to a clinical working model," says Paul Wentworth, Jr, Ph.D., who is a corresponding author on the paper.

The researchers are also now looking to formulate their synthetic glycoconjugate into a slow-release form that can be administered well in advance of major surgery, for instance, in the hope of someday providing outstanding protection to hospital patients.

The article, "Active Immunization with a Glycolipid Transition State Analog Protects against Endotoxic Shock," is authored by Lyn H. Jones, Laurence J. Altobell III, Mary T. MacDonald, Nicholas A. Boyle, Paul Wentworth, Jr., Richard A. Lerner, and Kim D. Janda and appears in the November 18, 2002 issue of the journal Angewandte Chemie.


###
This work was supported by The National Institutes of Health and The Skaggs Institute for Chemical Biology, and also funded through a Merck Science Initiative Research Fellowship.

Jason Bardi | EurekAlert!
Further information:
http://www.scripps.edu/

More articles from Health and Medicine:

nachricht Diabetes mellitus: A risk factor for early colorectal cancer
27.05.2020 | Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg

nachricht Ultra-thin fibres designed to protect nerves after brain surgery
27.05.2020 | Martin-Luther-Universität Halle-Wittenberg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New measurement exacerbates old problem

Two prominent X-ray emission lines of highly charged iron have puzzled astrophysicists for decades: their measured and calculated brightness ratios always disagree. This hinders good determinations of plasma temperatures and densities. New, careful high-precision measurements, together with top-level calculations now exclude all hitherto proposed explanations for this discrepancy, and thus deepen the problem.

Hot astrophysical plasmas fill the intergalactic space, and brightly shine in stellar coronae, active galactic nuclei, and supernova remnants. They contain...

Im Focus: Biotechnology: Triggered by light, a novel way to switch on an enzyme

In living cells, enzymes drive biochemical metabolic processes enabling reactions to take place efficiently. It is this very ability which allows them to be used as catalysts in biotechnology, for example to create chemical products such as pharmaceutics. Researchers now identified an enzyme that, when illuminated with blue light, becomes catalytically active and initiates a reaction that was previously unknown in enzymatics. The study was published in "Nature Communications".

Enzymes: they are the central drivers for biochemical metabolic processes in every living cell, enabling reactions to take place efficiently. It is this very...

Im Focus: New double-contrast technique picks up small tumors on MRI

Early detection of tumors is extremely important in treating cancer. A new technique developed by researchers at the University of California, Davis offers a significant advance in using magnetic resonance imaging to pick out even very small tumors from normal tissue. The work is published May 25 in the journal Nature Nanotechnology.

researchers at the University of California, Davis offers a significant advance in using magnetic resonance imaging to pick out even very small tumors from...

Im Focus: I-call - When microimplants communicate with each other / Innovation driver digitization - "Smart Health“

Microelectronics as a key technology enables numerous innovations in the field of intelligent medical technology. The Fraunhofer Institute for Biomedical Engineering IBMT coordinates the BMBF cooperative project "I-call" realizing the first electronic system for ultrasound-based, safe and interference-resistant data transmission between implants in the human body.

When microelectronic systems are used for medical applications, they have to meet high requirements in terms of biocompatibility, reliability, energy...

Im Focus: When predictions of theoretical chemists become reality

Thomas Heine, Professor of Theoretical Chemistry at TU Dresden, together with his team, first predicted a topological 2D polymer in 2019. Only one year later, an international team led by Italian researchers was able to synthesize these materials and experimentally prove their topological properties. For the renowned journal Nature Materials, this was the occasion to invite Thomas Heine to a News and Views article, which was published this week. Under the title "Making 2D Topological Polymers a reality" Prof. Heine describes how his theory became a reality.

Ultrathin materials are extremely interesting as building blocks for next generation nano electronic devices, as it is much easier to make circuits and other...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

Aachen Machine Tool Colloquium AWK'21 will take place on June 10 and 11, 2021

07.04.2020 | Event News

International Coral Reef Symposium in Bremen Postponed by a Year

06.04.2020 | Event News

 
Latest News

Selectively Reactivating Nerve Cells to Retrieve a Memory

02.06.2020 | Life Sciences

New experiment design improves reproducibility

02.06.2020 | Life Sciences

CeMM study reveals how a master regulator of gene transcription operates

02.06.2020 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>