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HCV vaccine using chimp adenovirus shows promise in healthy humans

VIENNA — Use of adenovirus derived from chimpanzees showed increased activity and sustainability of T cell activation in an early study of a vaccine for hepatitis C virus, according to new data presented during the International Liver Congress.

“Why do we need an HCV vaccine? Because acute and chronic infection are asymptomatic and people present with asymptomatic disease. Because the new oral antiviral drugs are not available to most people and are unlikely to meet elimination targets. ... And because HCV drugs do not protect from reinfection,” Ilaria Esposito, postdoctoral research fellow at the University of Oxford, said during her general session presentation. “This study has demonstrated, for the first time, the use of human invariant chain as adjuvant in humans in an HCV prophylactic vaccine and possibly in the future of human cancer vaccines.”

Esposito explained that T-cell vaccines can be based on adenoviral vectors, but the possibility of neutralization of human adenovirus led the research to using rare subtypes of adenovirus or chimpanzee adenovirus.

Based on preclinical animal studies linking MCH class II invariant chain (li) to an immunogen encoded by viral vectors enhanced immunogen-specific T-cell responses, Esposito and colleagues tested this in humans using viral vectors chimpanzee adenovirus 3 (ChAd3) and modified vaccinia virus Ankara (MVA) encoding the HCV non-structural immunogen (NSmut) linked to human (h)li.

Esposito reported on ChAd3-hliNSmut and MVA-hliNSmut given 8 weeks apart in 17 healthy volunteers aged 18 years to 65 years in two doses (n = 6; ChAd3-hliNSmut 5x109 /MVA-hliNSmut 5x107 viral particles[vp], n = 11; ChAd3-hliNSmut 2.5x1010/MVA-hliNSmut 2 x108vp).

“Both chimp adeno-3 and MVA-invariant chain were very well tolerated, and we don’t have any serious adverse reactions and no clinically significant differences between the two vaccination regimens,” Esposito said.

Beyond well tolerated, though, she showed increased activity in the T cells of the healthy volunteers.

“The inclusion of invariant chain in a viral vaccine induces a great and unprecedented T-cell response. ... We had stronger T-cell response at every timepoint,” Esposito said.

In looking at the breadth and longevity of the T-cell response, Esposito said there was a significantly broader response seen at peak post prime and at day 98 in individuals undergoing ChAd3-hliNS/MVA-hliNS vaccination compared with those receiving NS constructs. Additionally, significantly higher values were obtained for volunteers receiving invariant chain vaccinations.

“High HCV antigen specific T cells are induced, especially 1 to 4 weeks after boasting,” she said.

Lastly, Esposito showed that the memory of the responses was sustained.

“CD4 and CD8 T cell responses were polyfunctional and dominated by a strong interferon-gamma followed by TNF-alpha and IL-2 production,” Esposito said. “CD4 and CD8 T cell proliferation was sustained and enhanced at the end of the trial in invariant chain vaccine regimen” – by Katrina Altersitz

Reference:

Esposito I. GS-05. Presented at: International Liver Congress; April 10-14, 2019; Vienna, Austria.

Disclosures: Esposito reports no relevant financial disclosures.