HIV vaccines hinder immune response

Author:  Wang Andrew
Date:  November 2007

There is mounting evidence that some of the viral vector systems used in creating a proper vaccine can interfere with the host immune system and are thus too dangerous to use for vaccine development. The latest study from The Wistar Institute provides strong support for the idea that viral vector vaccines could cause more harm than good. Recent study from researchers at The Wistar Institute has made scientists re-evaluate efforts to develop an HIV vaccine.

Often, viral vaccines are designed and administered using what are known as viral vectors' – a tamed' virus that contains specific genetic components of the target virus. These vectors are used to give target cells the ability to produce antibodies against pathogen proteins, improving the host's ability to fight those pathogens when they are introduced.

Vector research has been one of the main targets of HIV vaccine development and efforts in creating a successful HIV vaccine have relied heavily on the ability of these vectors to transfer genetic material. However, the findings in this study have shown that at least one vaccine using an adeno-associated virus (AAV) directly hinders the immune response to HIV itself. The virus activates HIV-specific T-cells, as intended, but at the same time it critically impairs the same cells. More than one major HIV vaccine development project currently uses an AAV vector, so these findings are immediately significant.

"What do these results mean?", asks Dr. Hildegund C.J. Ertl, Director of the Wistar Institute Vaccine Center and senior author of the new study. "Put simply, they mean that AAV vaccines against HIV may potentially cause harm and that, without additional pre-clinical studies, they should not be used in humans."

Conducted in mice, the researchers used a typical vaccine regimen in the experiment. The immune system was primed with an experimental AAV vaccine and was followed by a booster immunization using other viral vectors. However, follow-up assays of the immune response showed that in all cases HIV-specific T-cells put up a meagre defence against infection, secreted very few cytokines (a chemical that helps activate the immune system) and could not replicate very quickly.

This data partly replicates a condition known as T-cell exhaustion, often seen in chronic infections such as HIV, Hepatitis B and C, and in some cancers, such as melanoma.

These findings bring new and unforeseen challenges to the development of a successful vaccine. Hopefully, new research will surface with a more positive outcome, but for now, efforts in HIV vaccine development with viral vectors will have to be reconsidered.

Written by Andrew Wang

Reviewed by Charley Wang

Published by Pooja Ghatalia