viruses Review To Include or Occlude: Rational Engineering of HCV Vaccines for Humoral Immunity Felicia Schlotthauer 1,2,†, Joey McGregor 1,2,† and Heidi E Drummer 1,2,3,* 1 Viral Entry and Vaccines Group, Burnet Institute, Melbourne, VIC 3004, Australia;
[email protected] (F.S.);
[email protected] (J.M.) 2 Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia 3 Department of Microbiology, Monash University, Clayton, VIC 3800, Australia * Correspondence:
[email protected]; Tel.: +61-392-822-179 † These authors contributed equally to this work. 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 gen- erate 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. Keywords: glycoprotein E2; vaccine development; humoral immunity Citation: Schlotthauer, F.; McGregor, J.; Drummer, H.E To Include or 1. Introduction Occlude: Rational Engineering of HCV Vaccines for Humoral Immunity. The development of direct-acting antiviral agents (DAA) with their ability to cure Viruses 2021, 13, 805. https:// infection in >95% of those treated was heralded as the key to eliminating hepatitis C globally.