New Gene Discovery Boosts HIV Vaccine Development

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Oregon Health & Science University researchers have made a significant step in developing an HIV vaccine. They identified a gene that could have hindered vaccine effectiveness in humans. The study, published on Oct. 11 in Science Immunology, helps remove another obstacle in HIV vaccine development and could aid in addressing other diseases like malaria and cancer.

Daniel Malouli, Ph.D., the lead author, explained that the team examined whether human cytomegalovirus (HCMV) has additional genes that could obstruct the immune response needed for the vaccine to work against HIV.

In earlier studies with nonhuman primates, the researchers found that vaccines based on rhesus CMV (RhCMV) produced unique T cell responses not seen with other vaccines. These responses are critical for the vaccine’s effectiveness against SIV, the virus commonly used to model HIV/AIDS in primates.

“To create a similar vaccine for clinical trials, we need our HCMV-based vaccines to elicit comparable T cell responses in humans,” Malouli said.

Human and rhesus CMV share similarities. OHSU researchers previously determined that RhCMV requires certain genes to be turned off to generate these unique immune responses. This research has been a collaborative effort led by Louis Picker, M.D., Klaus Früh, Ph.D., and Scott Hansen, Ph.D., over several decades.

The team has been developing this vaccine platform since the early 2000s. In 2016, their startup, TomegaVax, was acquired by Vir Biotechnology, which is now testing the platform in a human clinical trial for HIV, in collaboration with the National Institutes of Health and the Bill and Melinda Gates Foundation. Früh, Picker, and Hansen are corresponding authors of the recent study.

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Malouli’s research journey began in 2007 with Früh, focusing on ways to improve rhesus CMV-based vaccine vectors. He later joined Picker’s lab to investigate T cell responses and refine CMV vaccines for human testing. Now, he leads his own lab at OHSU’s Vaccine and Gene Therapy Institute.

For this latest study, researchers introduced 41 human CMV-specific genes into rhesus CMV and monitored immune responses in nonhuman primates. They discovered that the gene UL18 from HCMV only triggered standard responses. This is because UL18 interacts with an inhibitory receptor on T cells, blocking their reprogramming.

Following this research, Früh announced that the team has designed an HCMV-based HIV vaccine that excludes UL18 and other genes that could hinder effectiveness in humans.

“Our goal is to develop a new type of vaccine not only for HIV but also for cancer and other diseases,” Früh said.

Malouli emphasized the potential of their CMV vector system, stating, “The applicability of our vector system to other diseases is endless.”

Human clinical trials for the HIV vaccine, without UL18, are currently underway through Vir Biotechnology and the NIH.


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