Virus Used In HIV Vaccines Weakens Immune System

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Main Category: HIV / AIDS
Also Included In: Immune System / Vaccines
Article Date: 19 Nov 2007 - 3:00 PDT

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A new US study has shown that some of the viruses used as carriers in clinical trials for HIV-1 vaccines weaken the immune system and may do more harm than good.

Researchers primed the immune systems of laboratory mice by exposing them to fragments of HIV carried by rAAV (recombinant adeno-associated virus (rAAV) vector), a type that has been used recently in human trials. This resulted in the anticipated creation of special T cells against HIV, but they didn't work properly. They couldn't fight against infection, they didn't release enough cytokines to activate an appropriate immune response, and they didn't reproduce when exposed to HIV in a booster.

The study is the work of Dr Hildegund C.J. Ertl, director of the Wistar Institute Vaccine Center, an independent nonprofit biomedical research institute based in Philadelphia, Pennsylvania, and colleagues, and is published in the November 16th online issue of the Journal of Clinical Investigation.

Leading efforts in human trials to develop an HIV vaccine have depended on the use of viruses to carry scraps of HIV virus as a way to get the patient's immune system to make antibodies against HIV.

However, more recently, evidence has been coming forward that some of these viral "vectors" may weaken the immune system and should not be used.

This study from Ertl and colleagues gives further evidence of this, and suggests that some viral vectors could do more harm than good.

Ertl and colleagues found that while the rAAV based vaccine managed to stimulate the immune system to produce T cells specifically against HIV, as intended, those same T cells also undermined the immune system in various ways.

"Put simply", said Ertl, these results "mean that AAV vaccines against HIV may potentially cause harm and that, without additional pre-clinical studies, they should not be used in humans".

Using laboratory mice, Ertl and colleagues primed the immune system against HIV with an experimental rAAV based vaccine. Then, as would be done in a typical vaccine regimen, they followed this with a booster immunization using a vaccine based on another viral vector, adenovirus (Ad). They also carried out some booster immunizations using other viral vectors.

When they looked at the resulting immune response using follow up assays, they found that in all booster immunization cases, the HIV specific T cells induced by the rAAV vector were ineffective at preventing infection, regardless of time between prime and booster. The T cells protected poorly against HIV, they failed to secrete sufficient levels of cytokines, chemicals that stimulate the immume response, and they did not replicate sufficiently in response to the booster.

The results indicate a condition known as "T cell exhaustion", something that has been observed before with HIV, hepatitis B and hepatitis C, and some cancers like melanomas, said the researchers.

The researchers concluded that:

"Our data suggest that rAAV vectors induce functionally impaired T cells and could dampen the immune response to a natural infection."

Ertl questioned the rationale for injecting people with "a vaccine that's going to have a detrimental effect".

"AAV vaccines against HIV may do more harm than good by robbing people of their natural immune response to HIV," she warned.

"Recombinant adeno-associated virus vectors induce functionally impaired transgene product - specific CD8+ T cells in mice."
Shih-Wen Lin, Scott E. Hensley, Nia Tatsis, Marcio O. Lasaro, and Hildegund C.J. Ertl.
J. Clin. Invest., Published Online November 16, 2007.
doi:10.1172/JCI33138

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Written by: Catharine Paddock
Copyright: Medical News Today
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