Neutralizing activities of caprine antibodies towards conserved regions of the HCV envelope glycoprotein E2

Department of Microbial Biotechnology, National Research Center, Giza, Egypt.
Virology Journal (Impact Factor: 2.18). 08/2011; 8:391. DOI: 10.1186/1743-422X-8-391
Source: PubMed


Anti HCV vaccine is not currently available and the present antiviral therapies fail to cure approximately half of the treated HCV patients. 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. Antibodies were generated by vaccination of goats with synthetic peptides derived from HCV E2. Viral neutralizing capacity of the generated anti E2 antibodies was tested using in vitro assays. 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 to 4.5 fold higher than comparable titers of antibodies to the same epitopes in chronic HCV patients. In post infection experiments of native HCV into cultured Huh7.5 cells 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 varies considerably and success in the enrichment of neutralization epitope-specific antibodies may be accompanied by favorable results in combating HCV infection. Also, E2 conserved peptides p517 and p412 represent potential components of a candidate peptide vaccine against HCV infection.

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Available from: Mostafa K El Awady, Apr 03, 2014
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    • "The vaccine Cenv3 is composed of 3 envelop peptides (p315 from E1, p412 and p517 from E2) each was synthesized in an 8 multiple antigenic peptide (MAP) as previously described ([26] [12]). "
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    ABSTRACT: Antibody mediated neutralization and specific cell mediated immunity are necessary to combat HCV infection. Viral load reduction following administration of non adjuvanted envelope peptide vaccine was investigated in chronic HCV-infected patients who did not respond to interferon and ribavirin (IFN+RBV) treatment. The roles of humoral and cellular arms in viral load decline were examined and tolerability was evaluated. In an open-label study, patients with mild CHC (genotype 4a) were enrolled in 2 groups of 14 patients each; they received subcutaneous injections of Cenv3 at 648μg×3 monthly doses (group I) and 324μg×6 biweekly doses (group II). Vaccine sera were examined for specific antibody titers against vaccine epitopes by ELISA, HCV RNA levels by real-time PCR and specific CD4(+)/CD8(+) T lymphocytes by enzyme-linked immunospot assay (ELIspot). Safety of Cenv3 vaccination was tested on bases of changes in liver functions, kidney function and blood cell counts. Cenv3 induced significant in antibody mediated viral neutralization and cellular responses with remarkable decline of HCV RNA in about two thirds of patients under study. The product is safe and tolerable with slight improvement in liver functions and platelet counts. Although, humoral and cellular arms of the immune system are usually impaired in CHC, the selected envelope epitopes were able to induce responses sufficient to reduce significantly viral RNA concentrations in chronic HCV-infected patients shown to be non responders to standard of care treatment. The observed immunogenicity and tolerability of Cenv3 paves the road for further studies toward development of a prophylactic vaccine against HCV. The clinical trial was registered in the; under the identifier no.: NCT01718834.
    Vaccine 08/2013; DOI:10.1016/j.vaccine.2013.07.074 · 3.62 Impact Factor
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    • "In the case of HCV, broadly crossneutralizing Abs (bnAbs) are most effective when directed against highly conserved and functionally critical epitopes (e.g., the CD81-binding site) among different genotypes [17–27]. However the binding of these HCV bnAbs may be inhibited by the presence of non-nAbs that bind proximal to the critical residues [28–34]. This hypothesis is still controversial [26] but recent experiments support the existence of interfering Ab populations [35]. "
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    ABSTRACT: Vaccination strategies depend entirely on the appropriate responsiveness of our immune system against particular antigens. For this active immunization to be truly effective, neutralizing antibodies (nAbs) need to efficiently counter the infectivity or propagation of the pathogen. Some viruses, including HIV, are able to take advantage of this immune response in order to evade nAbs. This review focuses on viral immune evasion strategies that result directly from a robust immune response to infection or vaccination. A rationale for multi-Ab therapy to circumvent this phenomenon is discussed. Progress in the formulation, production, and regulatory approval of monoclonal antibodies (mAbs) is presented.
    Clinical and Developmental Immunology 06/2013; 2013:632893. DOI:10.1155/2013/632893 · 2.93 Impact Factor
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    ABSTRACT: This review considers the stages of the development of synthetic peptide vaccines against infectious agents, novel approaches and technologies employed in this process, including bioinformatics, genomics, proteomics, large-scale peptide synthesis, high-throughput screening methods, the use of transgenic animals for modelling human infections. An important role for the development and selection of efficient adjuvants for peptide immunogens is noted. Examples of synthetic peptide vaccine developments against three infectious diseases (malaria, hepatitis C, and foot-and-mouth disease) are given.
    Biochemistry (Moscow) Supplement Series B Biomedical Chemistry 12/2010; 57(1):14-30. DOI:10.1134/S1990750810040025
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