Enhanced immunogenicity of a conformational epitope of human T-lymphotropic virus type 1 using a novel chimeric peptide

• Published in: Vaccine Vol. 19; no. 9; pp. 1068 - 1081
• Main Authors: Frangione-Beebe, Melanie, Albrecht, Bjorn, Dakappagari, Naveen, Rose, R.Travis, Brooks, Charles L, Schwendeman, Steven P, Lairmore, Michael D, Kaumaya, Pravin T.P
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 08.12.2000; Elsevier
• Subjects: Amino Acid Sequence; Animals; Antibodies, Viral - biosynthesis; Biodegradable microspheres; Biological and medical sciences; Epitopes; Fundamental and applied biological sciences. Psychology; glycoprotein gp46; HTLV-1; human T-lymphotropic virus; Human T-lymphotropic virus 1 - immunology; Male; Measles virus - immunology; Mice; Mice, Inbred ICR; Microbiology; Molecular Sequence Data; Peptide Fragments - immunology; Peptide vaccines; Protein Folding; Rabbits; T-Lymphocytes, Cytotoxic - immunology; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, Synthetic - immunology; Viral Envelope Proteins - chemistry; Viral Envelope Proteins - immunology; Viral Fusion Proteins - immunology; Viral Vaccines - immunology; Virology; Biodegradable microspheres; HTLV-1; Peptide vaccines; Encapsulation; Delivery system; Microsphere; Antigenic determinant; Peptides; Rodentia; Glycoprotein; Retroviridae; Rabbit; Vaccine; Lagomorpha; Virus; Vertebrata; Mammalia; Immunogenicity; Mouse; HTLV-I virus; Virus envelope
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/S0264-410X(00)00340-6

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 α-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.