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Reuters Health Information: Adjuvanted viral-vectored vaccine promising against hepatitis C in early trial

Adjuvanted viral-vectored vaccine promising against hepatitis C in early trial

Last Updated: 2020-06-24

By Marilynn Larkin

NEW YORK (Reuters Health) - An anti-hepatitis C adjuvanted viral-vectored vaccine stimulated strong antiviral responses from T cells and was safe in a phase I trial.

"In Oxford in 2014, we tested this viral vaccine platform in a cohort of healthy volunteers and it was shown to be effective, inducing a high magnitude of T-cell response against the encoded antigen," Dr. Ilaria Esposito of the University of Oxford, UK, told Reuters Health by email. "These first results enforced the idea that T-cell immunity plays an important role against HCV infection. Our aim in this study was to enhance anti-HCV T-cell response and to improve the vaccine efficacy."

The researchers tested the MHC class II-associated invariant chain (Ii) molecule as an adjuvant fused with a viral vector to a conserved region of the HCV genome in a cohort of healthy volunteers. "The invariant chain is a self-molecule present in our body and responsible for the activation of a CD4-positive T cell response," Dr. Esposito explained. "Preclinical data...showed that the fusion of Ii to an encoded antigen in adenoviral vectors improves and enhances T cell immune response against the encoded HCV antigen."

"When we tested this vaccine in humans, we saw that the vaccination was well tolerated, without any development of anti-Ii T-cell or antibody response," she said, "and it enhances the magnitude, breadth and proliferative capacity of anti-HCV-specific T-cells."

As reported in Science Translational Medicine, the researchers tested the adjuvanted vaccine in 17 healthy volunteers; another 19 volunteers received the HCV vaccine without the adjuvant. The median age at first vaccination was 44; 47% of volunteers were women and 82%, Caucasian.

As Dr. Esposito noted, overall, the vaccinations were well tolerated, and those who received the adjuvanted vaccine had stronger anti-HCV immune responses compared with volunteers who received the vaccine that lacked the Ii adjuvant.

Dr. Esposito said, "It is possible to think in the future of using the invariant chain as a molecular adjuvant for COVID-19 vaccine, but it needs to be validated, because the enhancing effect of invariant chain is not universal and depends on the antigen, as well."

Going forward, she added, "We would increase the number of people to test the vaccine's efficacy and try to do a longer follow-up to assess the durability of this effect, which is an important criterion for effective prophylactic vaccine strategies. However, maximizing and maintaining T-cell induction for several months, as we showed in this study, may be useful for therapeutic vaccination strategies, as well."

"Our aim is also to design new immunogens that could target multiple HCV genotypes, and test (them) in humans," she concluded.

Dr. Sean Kelly, an assistant clinical professor in gastroenterology and transplant hepatology at The Ohio State University Wexner Medical Center in Columbus, commented in an email to Reuters Health, "These findings are exciting since developing vaccines for certain viruses, such as hepatitis C, has been very challenging."

"A hepatitis C vaccine would have the ability to indirectly prevent cancer, which also occurs with the hepatitis B vaccine and human papilloma virus (HPV) vaccine," he added. That said, he noted, the data need to be confirmed to ensure validity. In addition, moving from a small phase 1 study to the large phase 3 trials needed prior to approval "would take years in this case."

The study was funded in part by GSK.

SOURCE: https://bit.ly/2Vfng0B Science Translational Medicine, online June 17, 2020.

 
 
 
 
                               
 
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