JCI table of contents: March 20, 2008

BACTERIOLOGY: Antibodies protect against bacteria in the blood

In developed countries, infection with nontyphoidal strains of Salmonella bacteria (NTS) usually occurs through eating contaminated food and causes gastroenteritis. By contrast, in Africa, children under the age of 2 and HIV-infected adults usually develop an infection in the blood (bacteremia), which is fatal in almost a quarter of affected children. There is currently no vaccine against NTS and understanding the immune response that protects against NTS bacteremia is crucial if one is to be developed. New data, generated by Calman MacLennan and colleagues, has now identified a role for antibody in protection against NTS bacteremia in children from Malawi, leading to the suggestion that effective vaccines against NTS should induce the generation of protective antibody.

TITLE: The neglected role of antibody in protection against bacteremia caused by nontyphoidal strains of Salmonella in African children

AUTHOR CONTACT:
Calman A. MacLennan
University of Birmingham, Birmingham, United Kingdom.
Phone: 44-121-414-6944; Fax: 44-121-414-3599; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=33998

GENE THERAPY: Take heed: HOXB4 gene therapy causes leukemia in large animals

Individuals with a number of life-threatening genetic diseases of the immune system have been successfully treated by gene therapy — that is, they were infused with early precursors of immune cells that had the correct form of the defective gene delivered into them by agents known as retroviral vectors. However, some patients later developed leukemia. This slowed progress in the field and has led to detailed studies seeking to determine the mechanisms underlying the cause of leukemia and whether other genes that are candidates for gene therapy approaches might pose a similar risk. A new study, carried out by Hans-Peter Kiem and colleagues, at the Fred Hutchinson Cancer Research Center, Seattle, has now indicated that early precursors of immune cells that had the gene HOXB4 delivered into them by a gammaretroviral vector became leukemic in 2 of 2 dogs and 1 of 2 macaques. In vitro analysis established a clear link between HOXB4 expression and leukemia, leading the authors to conclude that the use of HOXB4-based gene therapy would probably carry a high risk of leukemia and that extreme caution is needed when considering gene therapy approaches. The need for caution is echoed in an accompany commentary by Andre Larochelle and Cynthia E. Dunbar, at the National Institutes of Health, Bethesda, who discuss how important large animal studies, such as those reported by Hans-Peter Kiem and colleagues, are to minimize the risk of adverse events in humans receiving gene therapy in the future.

TITLE: High incidence of leukemia in large animals after stem cell gene therapy with a HOXB4-expressing retroviral vector