Tips from the Journals of the American Society for Microbiology

June 19, 2007

Needle-free Vaccine May Protect Against C. Difficile Infection

Researchers from the U.S. and abroad have developed a transcutaneous (needle-free) vaccine delivered through a patch applied to the skin that protects mice from C. difficile infection. They report their findings in the June 2007 issue of the journal Infection and Immunity.

Clostridium difficile is the leading cause of nosocomial diarrhea worldwide with more than 300,000 cases reported each year in the U.S. alone. The recent emergence of a new highly virulent strain has increased the need for effective preventative treatment methods.

Toxins A and B are the two major virulence factors expressed by C. difficile. Toxin A initiates infection allowing toxin B to access underlying cells. In the study researchers developed a vaccine including anti-toxin A antibodies and transcutaneously immunized mice, some also with the cholera toxin and some without, over a period of 42 days. Mice immunized with both C. difficile toxin A and cholera toxin displayed prominent immune responses to both toxins and blood from immunized mice was capable of neutralizing C. difficile toxin A in a cell culture test.

"Our results suggest that transcutaneous immunization with C. difficile toxin A may be a feasible immunization strategy against C. difficile, an important cause of morbidity and mortality against which current preventative strategies are failing," say the researchers.

(C. Ghose, A. Kalsy, A. Sheikh, J. Rollenhagen, M. John, J. Young, S.M. Rollins, F. Qadri, S.B. Calderwood, C.P. Kelly, E.T. Ryan. 2007. Transcutaneous immunization with Clostridium difficile toxoid A induces systemic and mucosal immune responses and toxin A-neutralizing antibodies in mice. Infection and Immunity, 75. 6: 2826-2832).

Respiratory Tract Immunization May Protect Against Ebola Virus

A topical respiratory tract vaccine tested for the first time in a primate model may protect against Ebola virus infection. Researchers from the National Institutes of Health, Bethesda, MD and the Centers for Disease Control, Atlanta, GA report their findings in the June 2007 issue of the Journal of Virology.

Ebola virus is a highly contagious form of severe hemorrhagic fever with a mortality rate of up to 88% in humans. Because it can be transmitted by contact and aerosol route, it is also considered to be high risk for use as a biological weapon. With the respiratory route as the common portal of pathogen entry, intranasal vaccines may prove vital in preventative therapies.

In the study researchers developed a vaccine incorporating the human parainfluenza virus type 3 (HPIV3), a common pediatric respiratory pathogen, and administered it by respiratory route to rhesus monkeys. Some monkeys were immunized once and others twice, then all were challenged with a highly lethal dose of the Ebola virus. Results showed that a single immunization protected 88% of the animals against severe hemorrhagic fever and death, while all those receiving two doses not only survived but were symptom free and no detectable Ebola virus was found in the bloodstream.

"These data illustrate the feasibility of immunization via the respiratory tract against the hemorrhagic fever caused by Ebola virus," say the researchers. "To our knowledge, this is the first study in which topical immunization through respiratory tract achieved prevention of a viral hemorrhagic fever infection in a primate model."

(A. Bukreyev, P.E. Rollin, M.K. Tate, L. Yang, S.R. Zaki, W.J. Shieh, B.R. Murphy, P.L. Collins, A. Sanchez. 2007. Successful topical respiratory tract immunization of primates against Ebola virus. Journal of Virology, 81. 12: 6379-6388).

Bullfrogs May Serve as Hosts for E. coli O157:H7

For the first time researchers have identified American bullfrogs as potentially suitable hosts for E. coli O157:H7, a common source of food-borne illness. They report their findings in the June 2007 issue of the journal Applied and Environmental Microbiology.

Escherichia coli O157:H7 is a major food safety concern worldwide. Cattle are known reservoirs of the bacterium and researchers are now suggesting transmission to aquatic vertebrates, such as amphibians, occurs when infected cattle defecate in water sources. Infected tadpoles could then shed the pathogen and infect cattle drinking the contaminated water as well as vegetables if the water is used for irrigation.

In the study researchers orally inoculated American bullfrog tadpoles and metamorphs with E. coli O157:H7 and tested for infection after 14 days. Tadpoles, which were housed in flowthrough aquaria, did not become infected, however 54% of metamorphs tested positive after being housed in stagnant aquaria.

"Our results suggest that American bullfrog metamorphs could function as a 'spill-over' reservoir for E. coli O157:H7 and thus contribute to its persistence in aquatic environments," say the researchers. "Further, given that metamorphs are capable of dispersal, they may have a role in the epidemiology of this pathogen."

(M.J. Gray, S. Rajeev, D.L. Miller, A.C. Schmutzer, E.C. Burton, E.D. Rogers, G.J. Hickling. 2007. Preliminary evidence that American bullfrogs (Rana catesbeiana) are suitable hosts for Escherichia coli O157:H7. Applied and Environmental Microbiology, 73. 12: 4066-4068).

American Society for Microbiology

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