Immunization with two synthetic consensus constructs of hepatitis C virus (HCV) glycoproteins was found to elicit narrow, but not widely effective, virus-neutralizing antibodies in guinea pigs, according to the results of a model study published in the journal Antiviral Research.
Courtesy NIH
Researchers created two novel synthetic E2 glycoprotein immunogens (NotC1 and NotC2) using consensus nucleotide sequences deduced from samples of circulating genotype 1 HCV strains, according to Alexander W. Tarr, PhD, of the Nottingham (England) University Hospitals NHS Trust, and his colleagues.
Expression of these constructs in Drosophila melanogaster cells resulted in high yields of correctly folded, monomeric E2 proteins, which were used to immunize guinea pigs. Both proteins generated antibodies capable of neutralizing the H77 strain of HCV, although NotC1 elicited antibodies that were more potent at neutralizing virus entry. The two sets of glycoprotein-induced antibodies neutralized some HCV strains representing genotype 1, but not those strains representing genotype 2 or genotype 3.
“The broader objective of eliciting antibodies that neutralize patient strains representing multiple genotypes will require further refinement of immunization protocols. A vaccine construct comprising the consensus of a minimal CD81 binding domain might be able to focus the antibody response to conserved epitopes on E2. Additionally, boosting immunized animals with glycoproteins representing different strains might be required to focus the antibody response on to conserved conformational epitopes,” the researchers concluded.
The research was funded by the Medical Research Council, the NIHR Nottingham Biomedical Research Centre, and the European Union. Disclosures were not reported.
SOURCE: Tarr AW et al. Antiviral Research 2018;160:25-37.