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: Bacterial communities of female genital tract have impact on inflammation, HIV risk

Related Stories

Inoculating against science denial

Apr 27, 2015

Science denial has real, societal consequences. Denial of the link between HIV and AIDS led to more than 330,000 premature deaths in South Africa. Denial of the link between smoking and cancer has caused ...

Vaccines from a reactor

Mar 02, 2015

In the event of an impending global flu pandemic, vaccine production could quickly reach its limits, as flu vaccines are still largely produced in embryonated chicken eggs. Udo Reichl, Director at the Max ...

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 ...

Recommended for you

HIV reservoirs remain obstacles to cure

May 19, 2015

Antiretroviral therapy (ART) has proven lifesaving for people infected with HIV; however, the medications are a lifelong necessity for most HIV-infected individuals and present practical, logistical, economic ...

Microclinics help keep Kenyan HIV patients in care

May 18, 2015

A team led by researchers from UC San Francisco, Organic Health Response, and Microclinic International is reporting results of a study that showed significant benefits of microclinics—an innovative intervention ...

'Redesigned' antibodies may control HIV

May 18, 2015

With the help of a computer program called "Rosetta," researchers at Vanderbilt University have "redesigned" an antibody that has increased potency and can neutralize more strains of the AIDS-causing human ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.