Hexon-chimaeric adenovirus serotype 5 vectors circumvent pre-existing anti-vector immunity

Diane M. Roberts, Anjali Nanda, Menzo J. E. Havenga, Peter Abbink, Diana M. Lynch, Bonnie A. Ewald, Jinyan Liu, Anna R. Thorner, Patricia E. Swanson, Darci A. Gorgone, Michelle A. Lifton, Angelique A. C. Lemckert, Lennart Holterman, Bing Chen, Athmanundh Dilraj, Angela Carville, Keith G. Mansfield, Jaap Goudsmit and Dan H. Barouch ()
Additional contact information
Diane M. Roberts: Beth Israel Deaconess Medical Center, Harvard Medical School
Anjali Nanda: Beth Israel Deaconess Medical Center, Harvard Medical School
Menzo J. E. Havenga: Crucell Holland BV
Peter Abbink: Beth Israel Deaconess Medical Center, Harvard Medical School
Diana M. Lynch: Beth Israel Deaconess Medical Center, Harvard Medical School
Bonnie A. Ewald: Beth Israel Deaconess Medical Center, Harvard Medical School
Jinyan Liu: Beth Israel Deaconess Medical Center, Harvard Medical School
Anna R. Thorner: Beth Israel Deaconess Medical Center, Harvard Medical School
Patricia E. Swanson: Beth Israel Deaconess Medical Center, Harvard Medical School
Darci A. Gorgone: Beth Israel Deaconess Medical Center, Harvard Medical School
Michelle A. Lifton: Beth Israel Deaconess Medical Center, Harvard Medical School
Angelique A. C. Lemckert: Crucell Holland BV
Lennart Holterman: Crucell Holland BV
Bing Chen: Children's Hospital, Harvard Medical School
Athmanundh Dilraj: South African Medical Research Council
Angela Carville: New England Primate Research Center
Keith G. Mansfield: New England Primate Research Center
Jaap Goudsmit: Crucell Holland BV
Dan H. Barouch: Beth Israel Deaconess Medical Center, Harvard Medical School

Nature, 2006, vol. 441, issue 7090, 239-243

Abstract: A tailor-made viral vector Adenovirus 5 (Ad5) causes mild respiratory tract infections in humans but its main claim to fame is as a potential vaccine vector for key diseases such as HIV/AIDS and malaria. Its potential clinical utility is, however, hampered by the fact that about half of the population in developed countries and 90% in Africa have been exposed to Ad5 before and have built up immunity. A team based at Harvard Medical School and the Dutch biotechnology company Crucell has devised a way of circumventing this problem by replacing parts of an Ad5 viral capsid protein with those from a related virus, the much rarer Ad48 adenovirus. The strategy was effective in tests in mice and monkeys; if the work can be repeated in humans then modified Ad5 will be a strong candidate as a vector for vaccines and also for delivering gene therapy.

Date: 2006
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DOI: 10.1038/nature04721

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