The mysteries of the HIV vaccine candidate revealed 20 years later

About two decades after developing a new type of vaccine, researchers at Oregon Health & Science University are discovering why it stops and ultimately eliminates the form of HIV in monkeys, called SIV, in about half of non-primate primates. humans – and why it is a promising candidate to stop HIV in people.

In scientific articles that were published simultaneously today in journals Science and Scientific Immunology, the creators of the cytomegalovirus, or CMV, vaccine platform describe the unusual biological mechanisms by which it works.

The findings also helped to adjust VIR-1111, the experimental CMV-based HIV vaccine that was developed at OHSU and is now being evaluated in a Phase 1 clinical trial. The test is being conducted by Vir Biotechnology, which licensed the OHSU’s CMV vaccine platform technology.

“Knowing the mechanism that the CMV-based SIV vaccine uses to work in rhesus monkeys gives us a way to judge the potential of a human vaccine very quickly,” said Louis Picker, MD, associate director of the OHSU Institute of Vaccines and Gene Therapy and professor of molecular pathology / microbiology and immunology at OHSU School of Medicine. “If you have the wrong genes in the CMV vaccine, the critical immune response needed for effectiveness will not develop. You have to thread the needle on the CMV vaccine needle exactly if you want a high degree of protection, and you have to know what you’re looking for. “

Two of the articles describe that the cytomegalovirus vaccine needs to generate an unusual type of CD8-positive T cell response, called MHC-E restricted T cells, to effectively combat SIV in monkeys.

“We have known for some time that we have unusual T cell responses in monkeys receiving our CMV vaccine against SIV,” said Klaus Frueh, Ph.D., professor of molecular microbiology and immunology at the OHSU School of Medicine and OHSU Vaccine and Institute of Gene Therapy. “But we didn’t know if they were important for protection against SIV. This research clearly shows that without this special MHC-E restricted T cell response, we have no protection.”

The study published in Scientific Immunology shows that the vaccine was only able to generate these special T cells to fight SIV if eight specific genes were absent or inactivated in the natural form of monkey CMV. And a corresponding article published via ScienceThe First Release of Describes how a specific cytomegalovirus protein known as Rh67 is needed to generate MHC-E restricted T cells to protect against SIV. Together, these articles suggest how a CMV-based vaccine needs to be designed to create these unconventional T-cell responses.

And in a separate Scientific Immunology an article that was also published today, a research team led by Andrew J. McMichael, Ph.D., of the University of Oxford investigated whether what was learned from experiments on non-human primates could be transferred to humans. These researchers showed that MHC-E-restricted CD8-positive T cells could be increased and suppress HIV in laboratory cell cultures.

This new research is being published as the OHSU Genetic Therapy and Vaccine Institute celebrates the 20th anniversary of its first research building opened in April 2001. Picker and Frueh moved to Oregon to help start the institute: Picker leads their research program vaccines since its founding, and Frueh joined forces with Picker in 2006.