Back-to-front West Nile vaccine

A clever twist on the design of so-called DNA vaccines could provide improved protection against the dengue and West Nile viruses, suggests research published online this week in Nature Biotechnology.

As traditional vaccines containing small doses of weakened viruses can actually cause disease in rare cases, there are no approved vaccines to protect against the serious and potentially fatal diseases caused by these viruses. This safety concern can be eliminated using newer DNA vaccines, but it remains unclear whether these are able to stimulate our immune systems sufficiently to protect against viral infection.

Alexander Khromykh and colleagues show how to boost the potency of a DNA vaccine against West Nile virus by allowing infectious particles to be produced, but stopping their replication after one round of infection. They accomplish this by encoding the instructions for making live West Nile virus on a single DNA sequence that can be read in two different directions. In one direction, the cell�s enzymes translates these instructions into the coat protein used to package the genetic material of West Nile virus; in the other direction, the cell decodes the sequence into all the viral proteins except the coat protein.

Cells that take up the back-to-front DNA vaccine first stimulate the immune system just like a conventional DNA vaccine that doesn�t produce live, infectious virus. But because the coat protein produced in one direction can package the West Nile virus genome and other proteins encoded by the sequence in the other direction, a new population of viruses is produced that are released and infect adjacent cells, boosting immune stimulation. In the next cells, however, further infection is stopped as the viruses they contain lack coat protein necessary for packaging, therefore stopping the assembly of infectious virus.

The authors demonstrate protective responses to West Nile virus in mice and horses. The approach could also be effective in tackling other diseases caused by flaviviruses, such as dengue fever and dengue hemorrhagic fever.

Single-round infectious particles enhance immunogenicity of a DNA vaccine against West Nile virus pp 571 - 577

David C Chang, Wen J Liu, Itaru Anraku, David C Clark, Christopher C Pollitt, Andreas Suhrbier, Roy A Hall & Alexander A Khromykh

Published online: 20 April 2008 | doi 10.1038/nbt1400

Abstract | Full text | PDF | Supplementary Information