Viral-Vector Vaccines Vexed

Hopes for radical new vaccines using so-called viral vector technology have received a setback, with researchers reporting that the method may actually do more harm than good.

The new study, in the Journal of Clinical Investigation, found evidence that an HIV vaccine construct incorporating the adeno-associated virus (AAV) directly interferes with the immune system’s response to the HIV virus. Specifically, while it induces HIV-specific T cells, as intended, those cells are functionally impaired in important ways.

The scientists behind the study, from The Wistar Institute, believe that great caution should now be exercised with trials of viral-vector vaccines. “What do these results mean”” asks Hildegund C.J. Ertl, director of the Wistar Institute Vaccine Center. “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, using 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. “AAV vaccines against HIV may do more harm than good by robbing people of their natural immune response to HIV,” concluded Ertl.

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Source: The Wistar Institute

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