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      Memory T Cells in Flavivirus Vaccination

      review-article
      Author(s): 1 , 1 , 1 , 2 , 3 , 4 , *
      Publication date (Electronic):
      Journal: Vaccines
      Publisher: MDPI
      Keywords: flavivirus, memory T cells, vaccine

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          Abstract

          Flaviviruses include many medically important viruses, such as Dengue virus (DENV), Japanese encephalitis (JEV), tick-borne encephalitis (TBEV), West Nile (WNV), yellow fever (YFV), and Zika viruses (ZIKV). Currently, there are licensed human vaccines for DENV, JEV, TBEV and YFV, but not for WNV or ZIKV. Memory T cells play a central role in adaptive immunity and are important for host protection during flavivirus infection. In this review, we discuss recent findings from animal models and clinical trials and provide new insights into the role of memory T cells in host protective immunity upon vaccination with the licensed flavivirus vaccines.

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          Efficacy and Long-Term Safety of a Dengue Vaccine in Regions of Endemic Disease.

          Sri Hadinegoro, José Arredondo-García, Maria Capeding … (2015)
          A candidate tetravalent dengue vaccine is being assessed in three clinical trials involving more than 35,000 children between the ages of 2 and 16 years in Asian-Pacific and Latin American countries. We report the results of long-term follow-up interim analyses and integrated efficacy analyses.
          Article 0 comments Cited 412 times – based on 0 reviews     Review now
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            A protective role for dengue virus-specific CD8+ T cells.

            Alessandro Sette, Maya F Kotturi, Bjoern Peters … (2009)
            Infection with one of the four serotypes of dengue virus (DENV1-4) can result in a range of clinical manifestations in humans, from dengue fever to the more serious dengue hemorrhagic fever/dengue shock syndrome. Although T cells have been implicated in the immunopathogenesis of secondary infections with heterologous DENV serotypes, the role of T cells in protection against DENV is unknown. In this study, we used a mouse-passaged DENV2 strain, S221, to investigate the role of CD8(+) T cells in the immune response to primary DENV infection. S221 did not replicate well in wild-type mice, but did induce a CD8(+) T cell response, whereas viral replication and a robust CD8(+) T cell response were observed after infection of IFN-alpha/betaR(-/-) mice. Depletion of CD8(+) T cells from IFN-alpha/betaR(-/-) mice before infection resulted in significantly higher viral loads compared with undepleted mice. Mapping the specificity of the CD8(+) T cell response led to the identification of 12 epitopes derived from 6 of the 10 DENV proteins, with a similar immunodominance hierarchy observed in wild-type and IFN-alpha/betaR(-/-) mice. DENV-specific CD8(+) T cells produced IFN-gamma, TNF-alpha, expressed cell surface CD107a, and exhibited cytotoxic activity in vivo. Finally, immunization with four of the immunodominant CD8(+) T cell epitopes enhanced viral clearance. Collectively, our results reveal an important role for CD8(+) T cells in the host defense against DENV and demonstrate that the anti-DENV CD8(+) T cell response can be enhanced by immunization, providing rationale for designing DENV-specific vaccines that induce cell-mediated immunity.
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              B cells and antibody play critical roles in the immediate defense of disseminated infection by West Nile encephalitis virus.

              Michael S. Diamond, Bimmi Shrestha, Anantha Marri … (2003)
              West Nile virus (WNV) causes severe central nervous system (CNS) infection primarily in humans who are immunocompromised or elderly. In this study, we addressed the mechanism by which the immune system limits dissemination of WNV infection by infecting wild-type and immunodeficient inbred C57BL/6J mice with a low-passage WNV isolate from the recent epidemic in New York state. Wild-type mice replicated virus extraneuronally in the draining lymph nodes and spleen during the first 4 days of infection. Subsequently, virus spread to the spinal cord and the brain at virtually the same time. Congenic mice that were genetically deficient in B cells and antibody (microMT mice) developed increased CNS viral burdens and were vulnerable to lethal infection at low doses of virus. Notably, an approximately 500-fold difference in serum viral load was detected in micro MT mice as early as 4 days after infection, a point in the infection when low levels of neutralizing immunoglobulin M antibody were detected in wild-type mice. Passive transfer of heat-inactivated serum from infected and immune wild-type mice protected micro MT mice against morbidity and mortality. We conclude that antibodies and B cells play a critical early role in the defense against disseminated infection by WNV.
              Article 0 comments Cited 135 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Vaccines (Basel)
                Journal ID (iso-abbrev): Vaccines (Basel)
                Journal ID (publisher-id): vaccines
                Title: Vaccines
                Publisher: MDPI
                ISSN (Electronic): 2076-393X
                Publication date (Electronic): 18 October 2018
                Publication date Collection: December 2018
                Volume: 6
                Issue: 4
                Electronic Location Identifier: 73
                Affiliations
                [1 ]Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; guli@ 123456UTMB.EDU (G.L.); ccteleki@ 123456UTMB.EDU (C.T.)
                [2 ]Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA
                [3 ]Institute for Human Infections & Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA
                [4 ]Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA
                Author notes
                [* ]Correspondence: ti1wang@ 123456utmb.edu
                Author information
                https://orcid.org/0000-0002-7768-5584
                https://orcid.org/0000-0002-5922-1268
                Article
                Publisher ID: vaccines-06-00073
                DOI: 10.3390/vaccines6040073
                PMC ID: 6313919
                PubMed ID: 30340377
                SO-VID: dcad1927-a2f4-46ec-b63a-80449934ca2a
                Copyright © © 2018 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 16 August 2018
                Date accepted : 12 October 2018
                Categories
                Subject: Review

                Keywords: flavivirus,memory t cells,vaccine
                Data availability:
                Keywords: flavivirus, memory t cells, vaccine

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