Virus used to create experimental HIV vaccines directly impairs the immune response

Nov 15, 2007

Leading efforts to create an HIV vaccine have hinged on the use of viruses as carriers for selected elements of the HIV virus. Recently, however, evidence has emerged that some of these so-called viral vector systems may undermine the immune system and should not be used for vaccine development. Now, a new study from scientists at The Wistar Institute provides strong support for the idea that some viral-vector vaccines may cause more harm than good.

The findings show that an HIV vaccine construct incorporating one of these viruses, called adeno-associated virus, or AAV, directly interferes with the immune response to the HIV virus. Specifically, while it induces HIV-specific T cells, as intended, those cells are functionally impaired in important ways. At least one major HIV vaccine development project currently uses an AAV vector, so the findings are of immediate significance. A report on the study will be published online November 15 in the Journal of Clinical Investigation.

“What do these results mean?” asks Hildegund C.J. Ertl, M.D., director of the Wistar Institute Vaccine Center and senior author on 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.”

In the experiments, conducted in mice, the researchers used a typical vaccine regimen, priming the immune system with an experimental AAV vaccine against HIV and following it with a booster immunization using an HIV vaccine construct incorporating another viral vector called adenovirus, or Ad. Other viral vectors in addition to Ad were also tried as boosters.

Follow-up assays of the immune response showed that, in all cases, HIV-specific T cells induced by the AAV-vector only poorly protected from infection in a challenge model, failed to secrete adequate levels of important immune-system activating chemicals called cytokines, and most importantly were severely impaired in their ability to proliferate upon re-encounter with their antigen.

Taken together, the data partly outline a condition known as T-cell exhaustion, seen in a number of chronic infections, including HIV, hepatitis B, and hepatitis C, as well as in some cancers, such as melanoma.

“Why would you want to inject people with a vaccine that’s going to have a detrimental effect?” Ertl asks. “AAV vaccines against HIV may do more harm than good by robbing people of their natural immune response to HIV.”

Source: The Wistar Institute

Explore further: Animal study provides first evidence that gel can prevent multiple virus transmission in vagina/rectum

add to favorites email to friend print save as pdf

Related Stories

Mechanism of dengue virus entry into cells revealed

Feb 17, 2014

Dengue fever, an infectious tropical disease caused by a mosquito-borne virus, afflicts millions of people each year, causing fever, headache, muscle and joint pains and a characteristic skin rash. In some ...

HIV vaccine strategy expands immune responses

Mar 03, 2010

Two teams of researchers -- including Los Alamos National Laboratory theoretical biologists Bette Korber, Will Fischer, Sydeaka Watson, and James Szinger -- have announced an HIV vaccination strategy that has been shown to ...

Most detailed picture ever of key part of hepatitis C

Nov 28, 2013

Scientists at The Scripps Research Institute (TSRI) have determined the most detailed picture yet of a crucial part of the hepatitis C virus, which the virus uses to infect liver cells. The new data reveal ...

Recommended for you

HIV+ women respond well to HPV vaccine

Apr 16, 2014

HIV-positive women respond well to a vaccine against the human papillomavirus (HPV), even when their immune system is struggling, according to newly published results of an international clinical trial. The study's findings ...

User comments : 0

More news stories

Treating depression in Parkinson's patients

A group of scientists from the University of Kentucky College of Medicine and the Sanders-Brown Center on Aging has found interesting new information in a study on depression and neuropsychological function in Parkinson's ...

Airbnb rental site raises $450 mn

Online lodging listings website Airbnb inked a $450 million funding deal with investors led by TPG, a source close to the matter said Friday.

Health care site flagged in Heartbleed review

People with accounts on the enrollment website for President Barack Obama's signature health care law are being told to change their passwords following an administration-wide review of the government's vulnerability to the ...