Evading immunity

Credit: Courtesy of Dan Barouch" /> Credit: Courtesy of Dan Barouch The paper: D.M. Roberts et al., "Hexon-chimaeric adenovirus serotype 5 vectors circumvent preexisting antivector immunity," Nature, 441:239-243, 2006. (Cited in 52 papers) The finding: In 2006, Dan Barouch wanted to develop a vaccine vector that would not be suppressed by preexisting immunity. His gro

Elie Dolgin
May 1, 2008
<figcaption> Credit: Courtesy of Dan Barouch</figcaption>
Credit: Courtesy of Dan Barouch

The paper:

D.M. Roberts et al., "Hexon-chimaeric adenovirus serotype 5 vectors circumvent preexisting antivector immunity," Nature, 441:239-243, 2006. (Cited in 52 papers)

The finding:

In 2006, Dan Barouch wanted to develop a vaccine vector that would not be suppressed by preexisting immunity. His group at the Harvard Medical School and colleagues in the Netherlands constructed a chimeric adenovirus serotype 5 (Ad5) vector by swapping the hexon proteins in the capsid - the main target for antibodies - with proteins from the related Ad48 virus, which is less detectable by the immune system. As Barouch had hoped, these chimeras passed undetected into the bodies of mice and monkeys.

The impact:

Not only does this study produce a potentially effective vaccine vector, says John Mascola of the NIH's Vaccine Research Center, it's a "proof of principle that one can engineer a vector to avoid the immune...

The vaccine:

In 2007, Merck Research Laboratories halted Phase II trials of an HIV vaccine based on a nonchimeric Ad5 vector after the vaccine proved to be ineffective. Now, the NIH is planning to use a chimeric Ad5/Ad48 vector in HIV-vaccine Phase I trials, scheduled to begin in mid-2008.

Other uses:

Earlier this year, Andrew Baker of the University of Glasgow used the Ad5/Ad48 vector to show that the virus's hexon protein mediates the liver's uptake of adenoviruses. "Now that we know the mechanism of liver specificity, we can block it," says Baker, who is working to design tissue-specific vectors for delivering gene therapy.

Global Ad5 immunity
Ad5 seroprevalence in Western world: 30%-40%
Ad5 seroprevalence in developing world: 80%-90%