Abstract
Direct-acting antiviral agents have proven highly effective at treating existing hepatitis C infections but despite their availability most countries will not reach the World Health Organization targets for elimination of HCV by 2030. A prophylactic vaccine remains a high priority. Whilst early vaccines focused largely on generating T cell immunity, attention is now aimed at vaccines that generate humoral immunity, either alone or in combination with T cell-based vaccines. High-resolution structures of hepatitis C viral glycoproteins and their interaction with monoclonal antibodies isolated from both cleared and chronically infected people, together with advances in vaccine technologies, provide new avenues for vaccine development.
Highlights
The development of direct-acting antiviral agents (DAA) with their ability to cure infection in >95% of those treated was heralded as the key to eliminating hepatitis C globally.after more than 7 years of direct-acting antiviral therapy availability only nine countries will be able to eliminate hepatitis C by 2030 [1]
Glycoprotein E1 in itself does not appear to be a major target of the neutralizing antibodies (NAb) response in natural infection; instead, some NAb have been identified that require a heterodimer between E1 and E2 to form with antibody contact residues identified from within E1 [13]
Very limited studies are available on the role of such polyfunctional antibodies and antibody—dependent cellular cytotoxicity (ADCC) in Hepatitis C virus (HCV) infection
Summary
The development of direct-acting antiviral agents (DAA) with their ability to cure infection in >95% of those treated was heralded as the key to eliminating hepatitis C globally. A vaccine would confer ‘sterilizing’ immunity by inducing potent NAb responses towards the HCV envelope proteins of all genotypes/subtypes/quasispecies and a multi specific cellular immune response including both CD4+ and CD8+ T cells. In such a scenario, a prophylactic vaccine would prevent infection completely. The viral glycoproteins that are targets of the NAb response, known to prevent infection in vitro, and associated with viral clearance in vivo, possess multiple immune evasion mechanisms that suppress the generation of robust broadly reactive neutralizing (brNAb) responses These factors together with a preconception that DAAs will be sufficient to reach elimination resulting in a lack of investment in HCV vaccine research have stalled. Recent progress in understanding viral glycoprotein structure and how antibodies interact with the viral glycoproteins, suggest a pathway to vaccine development using novel technologies and protein engineering
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
