Prime-boost regimens with adjuvanted synthetic long peptides elicit T cells and antibodies to conserved regions of HIV-1 in macaques
| Autor: | Alice Mbewe-Mvula, Nicola Borthwick, Anne Bridgeman, Guillaume Stewart-Jones, Esther D. Quakkelaar, Jan W. Drijfhout, Cornelis J. M. Melief, David C. Montefiori, Andrew J. McMichael, Maximillian Rosario, Alfredo Nicosia, Tomáš Hanke, Stefano Colloca |
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| Přispěvatelé: | Rosario, M, Borthwick, N, Stewart Jones, Gb, Mbewe Mvula, A, Bridgeman, A, Colloca, S, Montefiori, D, Mcmichael, Aj, Nicosia, Alfredo, Quakkelaar, Ed, Drijfhout, Jw, Melief, Cj, Hanke, T. |
| Rok vydání: | 2011 |
| Předmět: |
Immunogen
HIV vaccine macaques Immunology T cells Immunization Secondary Vaccinia virus HIV Antibodies Lymphocyte Activation Virus prime-boost conserved region chemistry.chemical_compound Adjuvants Immunologic Immunology and Allergy Cytotoxic T cell antibodies Animals Cell Proliferation AIDS Vaccines Vaccines Synthetic biology macaque Virology synthetic long peptides Macaca mulatta Vaccination Infectious Diseases Electroporation antibodie chemistry synthetic long peptide DNA Viral biology.protein HIV-1 conserved regions Vaccinia Antibody |
| Zdroj: | AIDS, 26(3), 275-284 AIDS |
| ISSN: | 1473-5571 |
| Popis: | Objectives: Administration of synthetic long peptides (SLPs) derived from human papillomavirus to cervical cancer patients resulted in clinical benefit correlated with expansions of tumour-specific T cells. Because vaginal mucosa is an important port of entry for HIV-1, we have explored SLP for HIV-1 vaccination. Using immunogen HIVconsv derived from the conserved regions of HIV-1, we previously showed in rhesus macaques that SLP.HIVconsv delivered as a boost increased the breath of T-cell specificities elicited by single-gene vaccines. Here, we compared and characterized the use of electroporated pSG2.HIVconsv DNA (D) and imiquimod/montanide-adjuvanted SLP.HIVconsv (S) as priming vaccines for boosting with attenuated chimpanzee adenovirus ChAdV63.HIVconsv (C) and modified vaccinia virus Ankara MVA.HIVconsv (M). Design: Prime-boost regimens of DDDCMS, DSSCMS and SSSCMS in rhesus macaques. Methods: Animals' blood was analysed regularly throughout the vaccination for HIV-1-specific T-cell and antibody responses. Results: We found that electroporation spares DNA dose, both SLP.HIVconsv and pSG2.HIVconsv DNA primed weakly HIVconsv-specific T cells, regimen DDDCM induced the highest frequencies of oligofunctional, proliferating CD4 and CD8 T cells, and a subsequent SLP.HIVconsv boost expanded primarily CD4 cells. DSS was the most efficient regimen inducing antibodies binding to regions of trimeric HIV-1 Env, which are highly conserved among the four major global clades, although no unequivocal neutralizing activity was detected. Conclusion: The present results encourage evaluation of the SLP.HIVconsv vaccine modality in human volunteers along the currently trialled pSG2.HIVconsv DNA, ChAdV63.HIVconsv and MVA.HIVconsv vaccines. These results are discussed in the context of the RV144 trial outcome. © 2012 Wolters Kluwer Health Lippincott Williams and Wilkins. |
| Databáze: | OpenAIRE |
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