title: Enhanced immunogenicity of a conformational epitope of human T-lymphotropic virus type 1 using a novel chimeric peptide.
abstract: The ability of a peptide vaccine derived from the human T-lymphotropic virus type 1 (HTLV-1) surface envelope glycoprotein protein (gp46) to mimic the native protein and elicit a protective immune response has been examined. This peptide construct, designated MVFMF2, comprises amino acids (aa) 175-218 of gp46 linked by a four residue turn (GPSL) to a promiscuous T-cell epitope from the measles virus fusion protein (MVF, aa 288-302). The peptide was structurally characterized by circular dichroism (CD) spectroscopy and was found to contain alpha-helical secondary structure. The immunogenicity of MVFMF2 in rabbits and mice was evaluated by direct ELISA and competitive ELISA using peptide constructs and the recombinant protein ACH-RE3 (aa 165-306). This peptide, when administered with adjuvant (N-acetyl-glucosamine-3yl-acetyl-L-alanyl-D-isoglutamine, nor-MDP) was immunogenic in an outbred population of both rabbits and mice. Furthermore, the peptide construct was encapsulated in biodegradable microspheres of poly(D,L-lactide-co-glycolide) to eliminate booster immunization and to examine adjuvant requirements. The data indicate that MVFMF2 shows enhanced immunogenicity when encapsulated in biodegradable microspheres. Inoculation of the encapsulated peptide produced a similar humoral response to that of the free peptide, but did not require the use of adjuvant. Elicited anti-rabbit and anti-mouse antibodies recognized whole viral preparations and the recombinant protein ACH-RE3 in ELISA assays. Additionally, inoculated rabbits exhibited enhanced reactivity to viral antigens by western blot compared to non-vaccinated controls. Although anti-rabbit and anti-mouse antibodies were capable of inhibiting syncytium formation at low dilutions, rabbits were not protected from cell-associated viral challenge. Future development of vaccines to HTLV-1 may need to incorporate the ability to elicit cell-mediated immune responses in order to protect against cell-associated viral infection.
authors.affiliation: Ohio State Biochemistry Program, College of Biological Sciences, USA.
authors.forename: M
authors.initials: M
authors.lastname: Frangione-Beebe
authors.forename: B
authors.initials: B
authors.lastname: Albrecht
authors.forename: N
authors.initials: N
authors.lastname: Dakappagari
authors.forename: R T
authors.initials: RT
authors.lastname: Rose
authors.forename: C L
authors.initials: CL
authors.lastname: Brooks
authors.forename: S P
authors.initials: SP
authors.lastname: Schwendeman
authors.forename: M D
authors.initials: MD
authors.lastname: Lairmore
authors.forename: P T
authors.initials: PT
authors.lastname: Kaumaya
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000939:Epitopes; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D008297:Male; D008459:Measles virus / Q000276:immunology*; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D017510:Protein Folding; D011817:Rabbits; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology*; D014760:Viral Fusion Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000939:Epitopes; D010446:Peptide Fragments; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; D014765:Viral Vaccines