Recombinant HCV type 1 CORE+NS3 antigen(Capture)

Despite available treatments, a prophylactic HCV vaccine is needed to achieve elimination targets. HCV vaccine development has faltered largely because the extreme diversity of the virus limits the protective breadth of vaccine elicited antibodies. It is believed that the principle neutralizing epitope in natural infection, HVR1, which is the most variable epitope in HCV, mediates humoral immune escape. So far, efforts to circumvent HVR1 interference in the induction and function of conserved targeting Ab have failed. Efforts to understand factors contributing to cross-neutralization of HVR1 variants have also been limited. Here, following mouse immunizations with two patient-derived HVR1 peptides, we observe cross-genotype neutralization of variants differing at 15/21 positions. Surprisingly, sequence similarity was not associated with cross-neutralization. It appeared neutralization sensitivity was an intrinsic feature of each variant, rather than emergent from the immunogen specific Ab response. These findings provide novel insight into HVR1-mediated immune evasion, with important implications for HCV vaccine design.

Introduction Sexual acquisition has emerged as a transmission route for hepatitis C virus (HCV) of growing importance among human immunodeficiency virus (HIV)-positive populations. In Western countries, HCV epidemics have been increasingly detected among men who have sex with men (MSM). This review describes the molecular epidemiology of sexually acquired HCV infection in the Asia-Pacific region. Methods A systematic search was performed on PubMed in March 2019. Either abstract or full-text of each publication in the search results was screened for eligibility. Studies from different countries/cities involving eligible cases, who acquired HCV sexually with identified subtype, were synthesized for the evaluation of molecular epidemiology in the Asia-Pacific region. Two large-scale systematic reviews on the genotype distribution of HCV at a population level and among PWID were used as references for comparison. Results and discussion Overall, 13 full-text articles with 549 subjects originating from nine countries/cities were reviewed. A total of five genotypes and 14 subtypes were identified, dominated by subtypes 1b (23.0%), 2a (19.1%) and 3a (29.5%). A majority of the infected cases occurred in HIV-positive MSM. In some places, notably Hong Kong, India and Indonesia, the predominant subtype in sexually acquired HCV infection in MSM was different from that circulating in the general population. Shared transmission networks between people who inject drugs (PWID) and MSM were shown in Australia and New Zealand, whereas overlapping risk elicited from a small number of subjects existed in Tokyo, Taipei and Guangxi. MSM-specific clusters were identified in Hong Kong, Taipei and Hubei. Conclusions The distribution of sexually acquired HCV was sparsely scattered across countries/cities in the Asia-Pacific region. The threat of overlapping risk differed by locations, whereas transnational outbreaks remained uncommon. The paucity of information has hindered progress with comprehensive assessment in the Asia-Pacific region, where seroprevalence of HCV among HIV-positive MSM was relatively high.