HIV-1 T cell epitopes targeted to Rhesus macaque CD40 and DCIR: A comparative study of prototype dendritic cell targeting therapeutic vaccine candidates
| Autor: | Yves Levy, Rodolphe Thiébaut, Gerard Zurawski, Anthony D. Cristillo, Laura Richert, Andres M. Salazar, Lauren Hudacik, Sandra Zurawski, Aurélie Wiedemann, Monica Montes, Lindsey Galmin, Cécile Peltekian, Henri Bonnabau, Deborah T. Weiss, Christine Lacabaratz, Anne-Laure Flamar |
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| Přispěvatelé: | Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Advanced Bioscience Laboratories (ABL), Oncovir [Washington] |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
RNA viruses 0301 basic medicine Cellular immunity Modified vaccinia Ankara Epitopes T-Lymphocyte Antibody Response HIV Antibodies Monkeys Pathology and Laboratory Medicine White Blood Cells Immunodeficiency Viruses Animal Cells Medicine and Health Sciences Cytotoxic T cell Public and Occupational Health Molecular Targeted Therapy Receptors Immunologic Enzyme-Linked Immunoassays Immune Response AIDS Vaccines Mammals Vaccines Multidisciplinary T Cells Eukaryota Vaccination and Immunization 3. Good health Infectious Diseases medicine.anatomical_structure Medical Microbiology Viral Pathogens Viruses Vertebrates Medicine Cellular Types Pathogens Macaque Research Article Primates Infectious Disease Control Science Immune Cells T cell Immunology Cytotoxic T cells Research and Analysis Methods Microbiology 03 medical and health sciences Immune system Retroviruses Old World monkeys medicine Animals CD40 Antigens Immunoassays Antigen-presenting cell Microbial Pathogens Blood Cells business.industry Lentivirus Organisms Biology and Life Sciences HIV Dendritic Cells Cell Biology Dendritic cell Macaca mulatta 030104 developmental biology Amniotes HIV-1 Immunologic Techniques Preventive Medicine [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology business CD8 |
| Zdroj: | PLoS ONE PLoS ONE, 2018, 13 (11), pp.e0207794. ⟨10.1371/journal.pone.0207794⟩ PLoS ONE, Public Library of Science, 2018, 13 (11), pp.e0207794. ⟨10.1371/journal.pone.0207794⟩ PLoS ONE, Vol 13, Iss 11, p e0207794 (2018) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0207794⟩ |
| Popis: | International audience; HIV-1 infection can be controlled by anti-retroviral drug therapy, but this is a lifetime treatment and the virus remains latent and rapidly rebounds if therapy is stopped. HIV-1-infected individuals under this drug regimen have increased rates of cancers, cardiovascular diseases, and autoimmunity due to compromised immunity. A therapeutic vaccine boosting cellular immunity against HIV-1 is therefore desirable and, possibly combined with other immune modulating agents, could obviate the need for long-term drug therapies. An approach to elicit strong T cell-based immunity is to direct virus protein antigens specifically to dendritic cells (DCs), which are the key cell type for controlling immune responses. For eliciting therapeutic cellular immunity in HIV-1-infected individuals, we developed vaccines comprised of five T cell epitope-rich regions of HIV-1 Gag, Nef, and Pol (HIV5pep) fused to monoclonal antibodies that bind either, the antigen presenting cell activating receptor CD40, or the endocytic dendritic cell immunoreceptor DCIR. The study aimed to demonstrate vaccine safety, establish efficacy for broad T cell responses in both primed and naïve settings, and identify one candidate vaccine for human therapeutic development. The vaccines were administered to Rhesus macaques by intradermal injection with poly-ICLC adjuvant. The animals were either i) naïve or, ii) previously primed with modified vaccinia Ankara vector (MVA) encoding HIV-1 Gag, Pol, and Nef (MVA GagPolNef). In the MVA-primed groups, both DC-targeting vaccinations boosted HIV5pep-specific blood CD4+ T cells producing multiple cytokines, but did not affect the MVA-elicited CD8+ T cell responses. In the naive groups, both DC-targeting vaccines elicited antigen-specific polyfunctional CD4+ and CD8+ T cell responses to multiple epitopes and these responses were unchanged by a subsequent MVA GagPolNef boost. In both settings, the T cell responses elicited via the CD40-targeting vaccine were more robust and were detectable in all the animals, favoring further development of the CD40-targeting vaccine for therapeutic vaccination of HIV-1-infected individuals. |
| Databáze: | OpenAIRE |
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