Caprine antibodies towards E2 conserved peptides interfere with hepatitis C virus infectivity in vitro

Abstract

Background The reason (s) why human antibodies raised against hepatitis C virus (HCV) do not offer protection against multiple viral infections may be related to either genetic variations among viral strains particularly within the hypervariable region-1 (HVR-1), low titers of anti E2 antibodies or interference of non neutralizing antibodies with the function of neutralizing antibodies. Aim This study was designed to assess the immunogenic properties of genetically conserved peptides derived from the C-terminal region of HVR-1 and test their neutralizing activities in a step towards developing therapeutic and/or prophylactic immunogens against HCV infection. Materials and methods Goats immunized with E2 synthetic peptides termed p412 [a.a. 412–419], p430 [a.a. 430–447] and p517 [a.a. 517–531] generated high titers of antibody responses 2–4.5 fold higher than comparable titers of antibodies to the same epitopes in chronic HCV patients. Also p412 elicited approximately 3 fold increase in cell proliferation of specific antibody-secreting peripheral blood mononuclear cells (PBMC) from immunized caprines. When using in vitro culture model of Huh7.5 cell lines for infection and neutralization experiments anti p412 and anti p 517 were proven to be neutralizing to HCV genotype 4a from patients’ sera (87.5% and 75%, respectively). On the contrary anti p430 exhibited weak viral neutralization capacity on the same samples (31.25%). Furthermore Ab mixes containing anti p430 exhibited reduced viral neutralization properties. From these experiments one could predict that neutralization by Abs towards different E2-epitopes vary considerably and success in the enrichment of neutralization epitope-specific antibodies may be accompanied by favorable results in combating HCV infection. Conclusion Taking together the current results of humoral and cellular responses, we may suggest that E2 conserved peptides p517 and p412 represent essential components of a candidate peptide vaccine against HCV infection.