DNA immunization of mice and macaques with plasmids encoding hepatitis C virus envelope E2 protein expressed intracellularly and on the cell surface

We analyzed the humoral immune response elicited by hepatitis C virus (HCV) E2 protein expressed in vivo after injection of plasmid DNA into mice and rhesus macaques, Three plasmids were used for immunization: a plasmid conta ining the entire sequence of the E2 and p7 genes (pE2); a plasmid encoding a truncated form of the E2 protein targeted to the cell surface (pE2surf); a control plasmid (pDisplay) lacking an HCV insert. Each plasmid was inject ed intramuscularly into 5 mice and intraepidermally (via gene gun) into 5 m ice. Immunization was repeated three times at three week intervals. Five ma caques were injected intramuscularly (two with pE2., two with pE2surf and o ne with pDisplay) and immunization was repeated after 8 weeks. All mice imm unized via gene gun with pE2 or pE2surf developed anti-E2, the animals immu nized With pE2surf developed an earlier and stronger humoral immune respons e than those immunized with pE2.. Only 2 of the mice injected by the intram uscular route, both immunized with pE2surf, developed detectable anti-E2. O ne of the two macaques immunized with pE2 and both macaques immunized with pE2surf developed anti-E2; the humoral immune response was much stronger in the animals immunized with pE2surf. Our results suggest that presentation of HCV E2. on the cell surface may increase its immunogenicity while preser ving its ability to react with antibodies generated during a natural infect ion. Published by Elsevier Science Ltd.