title: Murine neutralizing antibody response and toxicity to synthetic peptides derived from E1 and E2 proteins of hepatitis C virus.
abstract: BACKGROUND
  The highest estimated prevalence of HCV infection has been reported in Egypt, nearly 12% mostly type 4. Currently, a commercial vaccine to protect this high risk population as well as global HCV infected patients is not available.
  
  
  OBJECTIVE
  In the present study, we aim at: (1) examining the viral binding capacities of purified monospecific polyclonal murine antibodies raised against genetically conserved viral protein sequences, i.e. synthetic peptides derived from those sequences located within envelope proteins and (2) assessment of immunogenic properties and safety parameters of those peptides individually and in a vaccine format in mice.
  
  
  METHODS
  Purified IgG Abs from immunized mice were used in immunocapture RT-PCR experiments to test viral neutralization by Abs raised against each of 4 peptides termed p35 (E1), p36 (E2), p37 (E2) and p38 (E2). Swiss mice were immunized with each of the 3 peptides (p35, p37 and p38) which generated neutralizing antibodies in immunocapture experiments. Antibody responses to corresponding peptides were determined using different routes of administration, different adjuvants, different doses and at different time points post-injection. To explore the dose range for future pharmacological studies, three doses namely 50 ng, 10 μg and 50 μg/25 gm mouse body weight were tested for biochemical and histopathological changes in several organs.
  
  
  RESULTS
  Murine Abs against p35, p37 and p38 but not p36 showed HCV neutralization in immunocapture experiments. Subcutaneous injection of peptides elicited higher responses than i.m. and i.p. Immunization with Multiple Antigenic Peptide (MAP) form or coupled to Al PO4 elicited the highest Ab responses. Peptide doses of 50 ng/25 gm body weight or less were effective and safe, however dose assessment still requires further study. Histopathological changes were observed in animals that received doses ∼1000 times higher than the potential therapeutic dose.
  
  
  CONCLUSIONS
  Exploration of humoral immunogenicity, neutralization capacity and safety suggested that the peptides presented herein are candidate vaccine components for further preclinical assessment.
authors.affiliation: Biomedical Technology Department, National Research Center, Tahrir Street 12622, Dokki, Cairo, Egypt. mkawady@yahoo.com
authors.forename: Mostafa K
authors.initials: MK
authors.lastname: El-Awady
authors.forename: Ashraf A
authors.initials: AA
authors.lastname: Tabll
authors.forename: Hassan
authors.initials: H
authors.lastname: Yousif
authors.forename: Yasmin
authors.initials: Y
authors.lastname: El-Abd
authors.forename: Mohamed
authors.initials: M
authors.lastname: Reda
authors.forename: Samy B
authors.initials: SB
authors.lastname: Khalil
authors.forename: Abdel Rahman
authors.initials: AR
authors.lastname: El-Zayadi
authors.forename: Maysa H
authors.initials: MH
authors.lastname: Shaker
authors.forename: Noha G
authors.initials: NG
authors.lastname: Bader El Din
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D005260:Female; D018937:Hepatitis C Antibodies / Q000097:blood*; D008297:Male; D051379:Mice; D014611:Vaccination / Q000379:methods; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014759:Viral Envelope Proteins / Q000008:administration & dosage / Q000276:immunology* / Q000633:toxicity; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; C087035:E1 protein, Hepatitis C virus; D018937:Hepatitis C Antibodies; D022223:Vaccines, Subunit; D014759:Viral Envelope Proteins; D014761:Viral Hepatitis Vaccines; C091015:glycoprotein E2, Hepatitis C virus