08 July 2012

New Magic Bullets Against Emerging and Chronic Infections?

Emerging infections -- both human engineered and naturally evolved -- present a difficult challenge for modern and future medicine. Recent scares from SARS and Bird Flu have sent journalists and health watchers into a frenzy, although fortunately neither outbreak proved as rapidly contagious and broadly lethal as anticipated -- so far.

A "magic bullet" that could provide resistance against a wide array of new viral, bacterial, and fungal infections would give medical practitioners and public health officials new confidence for a healthier human future.

Two potential "magic bullets" have been recently developed. The first is an artificial protein -- EP67 -- which appears to boost mammalian immune systems -- even when given alone without other drugs or vaccines.
Mice treated with EP67 within a twenty-four hour window of non-lethal infection were significantly protected from influenza-induced weight loss. Furthermore, EP67 delivered twenty-four hours after lethal infection completely blocked influenza-induced mortality (0% vs. 100% survival). Since protection based on innate immune induction is not restricted to any specific pathogen, EP67 may well prove equally efficacious against a wide variety of possible viral, bacterial, and fungal pathogens. Such a strategy could be used to stop the worldwide spread of emergent respiratory diseases, including but not limited to novel strains of influenza.

...In summary, this report shows that the C5a agonist peptide EP67 provides both prophylactic and therapeutic protection against influenza infection. Protection results from the rapid induction of a robust innate immune response that includes high local concentrations of anti-viral cytokines and the influx of several populations of innate immune effector cell types. These results have profound implications for influenza therapeutic development and, ultimately, for broad-spectrum emergency therapy against unidentified respiratory pathogens. _PLoS

Medical Express News Release on EP67

Another potential "magic bullet" approach to both new and old infectious diseases, is the T Cell vaccine.
For some infectious diseases, traditional vaccines just don't cut it. Microbes that hide inside human cells and cause chronic illness aren't stymied by the antibody response generated by the kind of vaccine available at the doctor's office. T-cell vaccines, which activate a different type of immune response, could, in theory, better prevent or control such chronic infections, but so far nobody has been successful at transitioning T-cell vaccines from the lab bench to the clinic.

A Cambridge, Massachusetts, biotech company called Genocea thinks its high-throughput method could change that. The company will begin its first clinical trial later this year, when its experimental herpes vaccine will be the first test of its claims.

All existing vaccines rouse the body into creating antibodies that attach to the surface of infecting microbes and flag them for destruction. But pathogens that live inside our cells, such as the viruses, bacteria, and other microbes that cause AIDS, malaria, herpes, and chlamydia, can evade this surveillance. "In order to deal with those types of pathogens, oftentimes we have to stimulate what we call cellular immunity. Unlike antibody immunity, which recognizes pathogens directly, cellular immunity has to recognize the infected cell and get rid of your own infected cells," says Darren Higgins, a biologist at Harvard Medical School who studies the interaction between hosts and pathogens and is a cofounder of Genocea.

... our understanding of how T cells control infection is still developing. The challenge is to identify the right protein—or antigen—from a pathogen that will grab a T cell's attention and signal that a human cell harbors an infectious agent. "If you can figure out what those protein pieces are, then you can use those proteins as a vaccine to sort of educate your immune system on what to respond to," says Higgins, who is now a consultant and scientific advisor for Genocea.

...Genocea plans to enter clinical trials with its genital herpes vaccine later this year. If successful, Genocea's herpes simplex 2 vaccine would be the first to combat the disease, which affects one out of every six people aged 15 to 49. Currently, patients can take antiviral drugs as a treatment, but there is no cure. Genocea's candidate vaccine would be used as a therapeutic treatment for patients who already have the disease.

Genocea's herpes vaccine program is moving faster than typical vaccine research, which can take 10 years to go from discovery to proof-of-concept and 20 years to reach the market, says Higgins. "Now you can screen very rapidly what is going to be the optimal vaccine component that allows you to get into clinical trials at a rapid rate." _TechnologyReview

These two distinct approaches to triggering immune system activity work on different parts of the immune system. EP67 protein induces an immediate immune response against acute threats. T Cell vaccines induce cellular immunity to destroy cells which are already infected, often chronically.

Human knowledge of the immune system was advanced significantly by the $billions spent on HIV / AIDS since the 1980s. Research tools and computational power have advanced along with this growing knowledge. Understanding the immune system better is one of the most important keys to effective treatment of a wide range of cancers, as well as to the development of effective anti-aging treatments.

Brian Wang looks at T Cell vaccines

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