Abstract
The reason(s) why human antibodies raised against hepatitis C virus (HCV) E2 epitopes 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. This study was designed to assess the immunogenic properties of genetically conserved peptides derived from the C-terminal region of HVR-1 as potential therapeutic and/or prophylactic vaccines against HCV infection. Goats immunized with E2-conserved synthetic peptides termed p36 (a.a 430–446), p37(a.a 517–531) and p38 (a.a 412–419) generated high titers of anti-p36, anti-p37 and anti-P38 antibody responses of which only anti- p37 and anti- p38 were neutralizing to HCV particles in sera from patients infected predominantly with genotype 4a. On the other hand anti-p36 exhibited weak viral neutralization capacity on the same samples. Animals super-immunized with single epitopes generated 2 to 4.5 fold higher titers than similar antibodies produced in chronic HCV patients. Also the studied peptides elicited approximately 3 fold increase in cell proliferation of specific antibody-secreting peripheral blood mononuclear cells (PBMC) from immunized goats. These results indicate that, besides E1 derived peptide p35 (a.a 315–323) described previously by this laboratory, E2 conserved peptides p37 and p38 represent essential components of a candidate peptide vaccine against HCV infection.
Highlights
Hepatitis C virus (HCV) infection is a global blood borne disease that affects almost 3% of the world's population with a morbidity and mortality rates that are second only to Human immunodeficiency virus (HIV) among the emerging infections [1]
Detection of reactive human IgGs towards the conserved E2 peptides in chronic hepatitis C virus (HCV) patients To answer the question whether the selected conserved E2-peptides were able to recognize specific immunoglobulins in chronic HCV patients, 100 chronic patients and 25 healthy controls were recruited for analysis of specific IgG titers
Using a cutoff of recognition calculated for each peptide, positive responses were obtained in 100 out of 100 (100%) chronic patients using either of the three peptides p36, p37 and p38
Summary
Hepatitis C virus (HCV) infection is a global blood borne disease that affects almost 3% of the world's population with a morbidity and mortality rates that are second only to HIV among the emerging infections [1]. Several investigators have focused on E2 glycoproteins (gps) for developing HCV vaccines including purified recombinant glycoproteins (gps) [15,16], modified viral vectors expressing HCV gps [17,18], recombinant virus like particles encoding HCV gp epitopes, and DNA constructs encoding HCV gps [19] These studies reported that anti-gp responses can be elicited (reviewed in Lechmann and Liang) [20]. Several observations support the hypothesis that neutralizing antibodies (nAb) may help control HCV replication These included (i) immunization of chimpanzees to elicit gp specific Ab responses induced sterilizing immunity against challenge with homologous virus [22,23]. We designed and synthesized conserved peptides from this domain used them to immunize goats and purified the goat antibodies for examining their immunogenic and neutralizing properties as candidates for further assessment of HCV peptide vaccine
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