Antigenic and immunogenic evaluation of permutations of soluble hepatitis C virus envelope protein E2 and E1 antigens

• DOI: 10.1371/journal.pone.0255336
• Publication Date: 2021-07-30T17:43:23Z
• Authors: Jannick Prentoe; Christoph M. Jani...; Rodrigo Velázquez...; Louise Goksøyr; Rebecca W. Olsen; Margherita Fanalista; Elias H. Augestad; Susan Thrane; Anne F. Pihl; Judith M. Gottwein; Adam F. Sander; Jens Bukh
• Keywords: Antigenicity; Hypervariable region

Yearly, about 1.5 million people become chronically infected with hepatitis C virus (HCV) and for the 71 chronic HCV infection 400,000 die from related morbidities, including liver cirrhosis cancer. Effective treatments exist, but challenges cost-of-treatment wide-spread undiagnosed infection, necessitates development of vaccines. Vaccines should induce neutralizing antibodies (NAbs) against envelope (E) transmembrane glycoprotein 2, E2, which partly depends on its interaction partner, E1, folding. Here, we generated three soluble protein antigens regions deleted (i.e., fused peptide backbones), termed sE1E2 (E1 followed by E2), sE2E1 (E2 E1), sE21E inverted E1). The E1 inversion positions C-terminal residues near is in analogy to how they likely interact native E1/E2 complexes. Probing conformational E2 epitope binding using patient-derived human monoclonal antibodies, show that was superior sE2E1, consistently sE1E2. This correlated improved induction NAbs compared especially female BALB/c mouse immunizations. deletion 27 N-terminal amino acids hypervariable region 1 (HVR1), conferred slight increases antigenicity sE21E, severely impaired able neutralize vitro viruses retaining HVR1. Finally, comparing sE2 immunizations, similar heterologous NAbs. In summary, find fusion or 1E fusion, both terms has relevance when designing E1E2 vaccine antigens.