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Tips from the Journals of the American Society for Microbiology
Date:9/22/2007

Phage Therapy May Control Staph Infections in Humans Including MRSA

Researchers from Italy have identified a bacteriophage active against Staphylococcus aureus, including methicillin-resistant strains, in mice and possibly humans. They report their findings in the August 2007 issue of the journal Antimicrobial Agents and Chemotherapy.

S. aureus is a highly flexible and potentially dangerous pathogen capable of causing skin abscesses, wound infections, endocarditis, osteomyelitis, pneumonia and toxic shock syndrome. Due to the organisms ability to live inside cells, emerging strains are increasingly resistant to antibiotics. Currently, forty to sixty percent of reported nosocomial S. aureus infections in the United States and the United Kingdom are multi-drug resistant with methicillin-resistant S. aureus carrying a significantly higher mortality rate.

A bacteriophage, or phage for short, is a virus that infects bacteria. In the study researchers identified the phage, MSa, and tested its activity against S. aureus in mice. Following simultaneous inoculation with both MSa and lethal and non-lethal doses of S. aureus results showed MSa rescued ninety-seven percent of mice from death and fully cleared mice of non-lethal bacterial infections.

These results suggest a potential use of the phage for the control of both local and systemic human S. aureus infections, say the researchers.

(R. Capparelli, M. Parlato, G. Borriello, P. Salvatore, D. Iannelli. 2007. Experimental phage therapy against Staphylococcus aureus in mice. Antimicrobial Agents and Chemotherapy, 51. 8: 2765-2773).


New Smallpox Vaccine Candidates Demonstrate Superior Immune Response, Efficacy and Safety in Mice

The integration of an immune-enhancing protein into two new smallpox vaccine candidates elicited superior immune responses, efficacy and safety in mice say researchers from the U.S. They report their findings in the August 2007 issue of the Journal of Virology.

Following the declaration of global eradication of smallpox in 1979, vaccinations for the general public were discontinued. Today, the virus poses threat as an agent of biological warfare, leaving half of the worldwide population susceptible to serious disease or death in the event of an attack. Severe adverse effects resulting from the currently licensed Dryvax vaccine emphasize the need for new preventative methods.

Researchers developed two new vaccine candidates integrating the immune-enhancing protein Interleukin-15 (IL-15) and tested for efficacy in mice lethally challenged with a neurovirulent western reserve strain of vaccinia. Wyeth IL-15 included a strain of the vaccinia virus derived from the Dryvax vaccine and MVA IL-15 incorporated a modified strain of the vaccinia virus Ankara which is currently being considered as a substitute for the Dryvax vaccine. The Wyeth IL-15 vaccine resulted in a 1,000-fold reduction in lethality and highly increased cellular and humoral immune responses. Additionally, mice vaccinated with Wyeth IL-15 fully survived a lethal intranasal challenge ten months after vaccination. The second candidate MVA IL-15 also demonstrated greater immunogenicity and efficacy than Dryvax.

By integrating IL-15 cytokine into Wyeth and MVA strains, we have developed two smallpox vaccine candidates with greater immunogenicity and efficacy yet with more-attenuated virulence than the currently licensed Dryvax vaccine suitable for contemporary populations, say the researchers.

(L.P. Perera, T.A. Waldmann, J.D. Mosca, N. Baldwin, J.A. Berzofsky, S.K. Oh. 2007. Development of smallpox vaccine candidates with integrated interleukin-15 that demonstrate superior immunogenicity, efficacy, and safety in mice. Journal of Virology, 81. 16: 8774-8783).


First Animal Model Developed for Oral Infection of Human Poliovirus

For the first time researchers have developed an animal model for oral poliovirus infection. They report their findings in the August 2007 issue of the Journal of Virology.

Poliovirus causes acute disease in the central nervous system in humans often resulting in paralysis. Due to its reemerging presence in developing countries researchers are reexamining the viruses ability to spread among humans through oral ingestion and develop new preventative therapies accordingly.

Due to the human digestive tracts low sensitivity to the poliovirus, no previous rodent model tracking oral infection has been developed. In the study mice carrying the human poliovirus receptor gene and lacking the interferon receptor gene (IFNAR) were sensitive to an oral challenge of the poliovirus. Nine days following the challenge the mice had died and the virus was detected in their small intestines and digestive tracts. Mice expressing the interferon receptor gene were found to be much less sensitive to virus.

These results suggest that IFNAR plays an important role in determining permissivity in the alimentary tract as well as the generation of virus-specific immune responses to poliovirus via the oral route, say the researchers. Thus, hPVR-Tg/IfnarKO are considered to be the first oral infection model for poliovirus.

(S. Ohka, H. Igarashi, N. Nagata, M. Sakai, S. Koike, T. Nochi, H. Kiyono, A. Nomoto. 2007. Establishment of a poliovirus oral infection system in human poliovirus receptor-expressing transgenic mice that are deficient in alpha/beta interferon receptor. Journal of Virology, 81. 15: 7902-7912).


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Contact: Carrie Patterson
cpatterson@asmusa.org
American Society for Microbiology
Source:Eurekalert

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