Induction of neutralizing antibody and T-cell responses to Varicella-zoster virus (VZV) using Ty-virus-like particles carrying fragments of glycoprotein E (gE)

Abstract During infection with Varicella-zoster virus (VZV), the envelope proteins are highly immunogenic and glycoprotein E (gE) is one of the most abundant and antigenic. We have previously identified the immunodominant regions of gE and mapped the B-cell epitopes. In this study, we have evaluated the immunogenicity of recombinant hybrid Ty-virus-like particles (VLPs) carrying amino acids (1–134) or (101–161) of gE which contain the immunodominant sequences. VZV-specific antibodies were detected by ELISA in sera from mice and guinea pigs immunized with either gE(1–134)-VLPs or gE(101–161)-VLPs. The dominant B-cell epitopes, mapped by pepscan analysis of the sera, were found in peptides spanning amino acids 41–60, 56–75, 101–120, 116–135, 131–150 and 141–161. These sera also showed neutralizing activity against VZV in vitro . Epitopes recognized by neutralizing MAbs were mapped to both gE sequences (3B3 MAb recognizing amino acids 141–161 and IFB9 MAb recognizing amino acids 71–90). Lymphocyte proliferative responses to VZV were detected in four different mouse strains immunized with either gE(1–134)-VLPs or gE(101–134)-VLPs in alum. All mouse strains immunized with gE(1–134)-VLPs recognized epitopes in amino acids 11–30 and 71–90 and all those immunized with gE(101–161)-VLPs recognized epitopes in amino acids 91–110 and 106–125. These results indicate that VLPs carrying these gE sequences can prime potent humoral and cellular anti-VZV responses in small animals and warrent further investigation as potential vaccine candidates against varicella-zoster infections.