A prophylactic hepatitis C virus (HCV) vaccine produces a long-lasting, sustained T-cell response that is characteristic of the T-cell response associated with a controlled HCV infection. Researchers have evaluated the vaccine in humans, and it is now ready for phase 2 efficacy studies.
Leo Swadling, a graduate student in the Nuffield Department of Medicine at the University of Oxford in the United Kingdom, and colleagues published the results from the phase 1 trial published online November 5 in Science Translational Medicine. They described their heterologous T-cell vaccine, which combines replication-defective chimpanzee adenovirus (ChAd3) and modified vaccinia Ankara (MVA) vectors, both encoding the HCV nonstructural (NS) proteins. The vaccine is referred to as ChAd3/MVA.
T-cell immunity appears to be critical in protection against natural infection from HCV. In particular, CD4+ T cells generate the CD8+ T-cell immunity that is associated with HCV viral control in both natural infection in humans and chimpanzee challenge studies. Thus, vaccinologists anticipate that an effective HCV vaccine will generate a robust T-cell response.
The ChAd3/MVA vaccine induced a large HCV-specific T-cell response in humans. In most individuals, vaccination induced T-cell responses against all six NS antigenic pools. Vaccination also increased CD8+ T-cell polyfunctionality. The investigators found no signs that the vaccine induced regulatory T cells that might suppress an anti-HCV immune response.
Vaccinated individuals possessed antigen-experienced T cells that were on a continuum from naive to memory populations. Vaccinated individuals also generated CD8+ memory T cells. All told, the phenotype of T cells after vaccination with ChAd3/MVA resembled T-cell populations after vaccination with the highly efficacious yellow fever and smallpox vaccines.
The ChAd3/MVA vaccine appeared to be significantly better than the previously tested ChAd3/Ad6 vaccine. It elicited a higher magnitude of T-cell response immediately, as well as long term after boost immunization.
The diversity of the HCV genome represents an additional barrier to the development of protective HCV vaccine. ChAd3/MVA appears to overcome this barrier though generation of cross-reactive T-cell responses between heterologous viral genotypes.
“I am impressed by the ability of this combination of ChAd3 prime/MVA boost with the NSmut HCV sequence to recapitulate the natural human immune response to HCV infection, to sustain a strong response, and to impart some cross-reactive response to other HCV genotypes. On a public health note, development of a vaccine against HCV has traditionally been challenging and the disease burden remains significant in the US. In particular, the disease is generally asymptomatic initially but has a high probability to become chronic, leading to bad outcomes,” Litjen Tan, PhD, from the Immunization Action Coalition in St. Paul, Minnesota, told Medscape Medical News.