Novel conjugates of epitope fusion peptides with CpG-ODN display enhanced immunogenicity and HIV recognition

Vaccination strategies remain elusive that are effective against viral disease pathogens yet remain gentle enough for widespread human use. We developed a model system that relies on the recognition of specific T-cell epitopes from immunodominant antigens of HIV to explore single-stranded CpG-oligod...

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Bibliographic Details
Published in:Vaccine 2005-05, Vol.23 (26), p.3453-3468
Main Authors: Daftarian, Pirouz, Sharan, Rahul, Haq, Wahajul, Ali, Saima, Longmate, Jeff, Termini, John, Diamond, Don J.
Format: Article
Language:English
Subjects:
Acquired immune deficiency syndrome
AIDS
Animals
Applied microbiology
Biological and medical sciences
Charitable foundations
CpG
Cytotoxicity
Deoxyribonucleic acid
DNA
Epitope
Epitopes - immunology
Fundamental and applied biological sciences. Psychology
HIV - drug effects
HIV - immunology
Immunity - drug effects
Immunogenicity
Infectious diseases
Laboratory animals
Lymphocytes
Mice
Microbiology
Miscellaneous
Molecular weight
Oligodeoxyribonucleotides - immunology
Oligodeoxyribonucleotides - pharmacology
Peptide Fragments - immunology
Peptides
Plasmids
Proteins
Public health
Smallpox
Vaccine
Vaccines
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
Viral diseases
Virology
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Summary:Vaccination strategies remain elusive that are effective against viral disease pathogens yet remain gentle enough for widespread human use. We developed a model system that relies on the recognition of specific T-cell epitopes from immunodominant antigens of HIV to explore single-stranded CpG-oligodeoxynucleotides (ODN) (CpG) as an adjuvant. We improved upon current strategies of utilizing CpG in combination with peptide vaccines by covalently modifying epitope fusion peptides with CpG motifs. Characterization of the immune recognition of DNA–peptide conjugates was carried out in a murine model of human HLA A2. Immunogenicity of DNA–peptide conjugates was superior in sensitivity to non-covalently linked mixtures of the same functional molecules as measured by peptide-mediated cytotoxicity and IFN-γ release, as well as protection against viral infection. Enhancement of sensitivity of immune recognition by covalent attachment of DNA to epitope peptides should be further evaluated as a novel prophylactic vaccine strategy for HIV infection and other infectious diseases.
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2005.01.093