Immunization with DNA Plasmids Coding for Crimean-Congo Hemorrhagic Fever Virus Capsid and Envelope Proteins and/or Virus-Like Particles Induces Protection and Survival in Challenged Mice
| Autor: | Sara Åkerström, Ola Blixt, Janusz T. Paweska, Mehrdad Mousavi-Jazi, Christian Risinger, Sándor Bereczky, Friedemann Weber, Jorma Hinkula, Ali Mirazimi, Caroline Vernersson, Helen Karlberg, Eva Wattrang, Alejandro Brun, Petrus Jansen van Vuren, Gunnel Lindegren, Stephanie Devignot |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Immunology Neutralizing antibodies Microbiology Virus DNA vaccination Microbiology in the medical area DNA vaccines 03 medical and health sciences Crimean-Congo hemorrhagic fever virus Th1/Th2 responses VLP neutralizing antibodies Mice Immune system Immunogenicity Vaccine Th2 Cells Viral Envelope Proteins Immunity Virology Vaccines and Antiviral Agents Mikrobiologi inom det medicinska området Vaccines DNA Animals Humans Vaccines Virus-Like Particle Neutralizing antibody Mice Knockout Immunity Cellular biology Immunogenicity Interferon-alpha Th1 Cells Antibodies Neutralizing 3. Good health Disease Models Animal 030104 developmental biology Insect Science Hemorrhagic Fever Virus Crimean-Congo biology.protein Epitopes B-Lymphocyte Capsid Proteins Hemorrhagic Fever Crimean Immunization Antibody Crimean Congo hemorrhagic fever virus Plasmids |
| Zdroj: | Journal of Virology Hinkula, J, Devignot, S, Åkerström, S, Karlberg, H, Wattrang, E, Bereczky, S, Mousavi-Jazi, M, Risinger, C W, Lindegren, G, Vernersson, C, Paweska, J, van Vuren, P J, Blixt, K O, Brun, A, Friedemann, W & Mirazimi, A 2017, ' Immunization with DNA plasmids coding for crimean-congo hemorrhagic fever virus capsid and envelope proteins and/or virus-like particles induces protection and survival in challenged mice ', Journal of Virology, vol. 91, no. 10, e02076-16 . https://doi.org/10.1128/JVI.02076-16 Repositorio de Resultados de Investigación del INIA Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria INIA INIA: Repositorio de Resultados de Investigación del INIA |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/JVI.02076-16 |
| Popis: | Crimean-Congo hemorrhagic fever virus (CCHFV) is a bunyavirus causing severe hemorrhagic fever disease in humans, with high mortality rates. The requirement of a high-containment laboratory and the lack of an animal model hampered the study of the immune response and protection of vaccine candidates. Using the recently developed interferon alpha receptor knockout (IFNAR −/− ) mouse model, which replicates human disease, we investigated the immunogenicity and protection of two novel CCHFV vaccine candidates: a DNA vaccine encoding a ubiquitin-linked version of CCHFV Gc, Gn, and N and one using transcriptionally competent virus-like particles (tc-VLPs). In contrast to most studies that focus on neutralizing antibodies, we measured both humoral and cellular immune responses. We demonstrated a clear and 100% efficient preventive immunity against lethal CCHFV challenge with the DNA vaccine. Interestingly, there was no correlation with the neutralizing antibody titers alone, which were higher in the tc-VLP-vaccinated mice. However, the animals with a lower neutralizing titer, but a dominant cell-mediated Th1 response and a balanced Th2 response, resisted the CCHFV challenge. Moreover, we found that in challenged mice with a Th1 response (immunized by DNA/DNA and boosted by tc-VLPs), the immune response changed to Th2 at day 9 postchallenge. In addition, we were able to identify new linear B-cell epitope regions that are highly conserved between CCHFV strains. Altogether, our results suggest that a predominantly Th1-type immune response provides the most efficient protective immunity against CCHFV challenge. However, we cannot exclude the importance of the neutralizing antibodies as the surviving immunized mice exhibited substantial amounts of them. IMPORTANCE Crimean-Congo hemorrhagic fever virus (CCHFV) is responsible for hemorrhagic diseases in humans, with a high mortality rate. There is no FDA-approved vaccine, and there are still gaps in our knowledge of the immune responses to infection. The recently developed mouse models mimic human CCHF disease and are useful to study the immunogenicity and the protection by vaccine candidates. Our study shows that mice vaccinated with a specific DNA vaccine were fully protected. Importantly, we show that neutralizing antibodies are not sufficient for protection against CCHFV challenge but that an extra Th1-specific cellular response is required. Moreover, we describe the identification of five conserved B-cell epitopes, of which only one was previously known, that could be of great importance for the development of diagnostics tools and the improvement of vaccine candidates. |
| Databáze: | OpenAIRE |
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