HIV-1 subtype C Pr55gag virus-like particle vaccine efficiently boosts baboons primed with a matched DNA vaccine
| Autor: | Carolyn Williamson, Alisson Lynch, Gerald K. Chege, Ann E. Meyers, Clive M. Gray, Enid G. Shephard, Edward P. Rybicki, Anna-Lise Williamson, Joanne van Harmelen |
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| Rok vydání: | 2008 |
| Předmět: |
viruses
Molecular Sequence Data Immunization Secondary HIV Antibodies Biology complex mixtures Peripheral blood mononuclear cell Virus DNA vaccination Interferon-gamma Papio ursinus Virus-like particle Virology Vaccines DNA medicine Animals Interferon gamma Amino Acid Sequence Lymphocytes Protein Precursors Antigens Viral AIDS Vaccines ELISPOT Virion biology.organism_classification Genes gag Peptide Fragments Immunology Lentivirus HIV-1 biology.protein Cytokines Antibody medicine.drug |
| Zdroj: | Journal of General Virology. 89:2214-2227 |
| ISSN: | 1465-2099 0022-1317 |
| DOI: | 10.1099/vir.0.83501-0 |
| Popis: | A DNA vaccine expressing human immunodeficiency virus type 1 (HIV-1) southern African subtype C Gag (pTHGag) and a recombinant baculovirus Pr55gagvirus-like particle prepared using a subtype C Pr55gagprotein (Gag VLP) was tested in a prime–boost inoculation regimen in Chacma baboons. The response of five baboons to Gag peptides in a gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay after three pTHGag immunizations ranged from 100 to 515 spot-forming units (s.f.u.) per 106peripheral blood mononuclear cells (PBMCs), whilst the response of two baboons to the Gag VLP vaccine ranged from 415 to 465 s.f.u. per 106PBMCs. An increase in the Gag-specific response to a range of 775–3583 s.f.u. per 106PBMCs was achieved by boosting with Gag VLPs the five baboons that were primed with pTHGag. No improvement in Gag responses was achieved in this prime–boost inoculation regimen by increasing the number of pTHGag inoculations to six. IFN-γresponses were mapped to several peptides, some of which have been reported to be targeted by PBMCs from HIV-1 subtype C-infected individuals. Gag VLPs, given as a single-modality regimen, induced a predominantly CD8+T-cell IFN-γresponse and interleukin-2 was a major cytokine within a mix of predominantly Th1 cytokines produced by a DNA–VLP prime–boost modality. The prime–boost inoculation regimen induced high serum p24 antibody titres in all baboons, which were several fold above that induced by the individual vaccines. Overall, this study demonstrated that these DNA prime/VLP boost vaccine regimens are highly immunogenic in baboons, inducing high-magnitude and broad multifunctional responses, providing support for the development of these products for clinical trials. |
| Databáze: | OpenAIRE |
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