Cell-Mediated Immunity Generated in Response to a Purified Inactivated Vaccine for Dengue Virus Type 1

ABSTRACT Dengue is the most prevalent arboviral disease afflicting humans, and a vaccine appears to be the most rational means of control. Dengue vaccine development is in a critical phase, with the first vaccine licensed in some countries where dengue is endemic but demonstrating insufficient effic...

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Autores principales:	Heather Friberg, Luis J. Martinez, Leyi Lin, Jason M. Blaylock, Rafael A. De La Barrera, Alan L. Rothman, J. Robert Putnak, Kenneth H. Eckels, Stephen J. Thomas, Richard G. Jarman, Jeffrey R. Currier
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	CMI PIV T cells dengue vaccine Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/9a70ddf949f2464fbfa4032091e25a8f
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spelling	oai:doaj.org-article:9a70ddf949f2464fbfa4032091e25a8f2021-11-15T15:27:52ZCell-Mediated Immunity Generated in Response to a Purified Inactivated Vaccine for Dengue Virus Type 110.1128/mSphere.00671-192379-5042https://doaj.org/article/9a70ddf949f2464fbfa4032091e25a8f2020-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00671-19https://doaj.org/toc/2379-5042ABSTRACT Dengue is the most prevalent arboviral disease afflicting humans, and a vaccine appears to be the most rational means of control. Dengue vaccine development is in a critical phase, with the first vaccine licensed in some countries where dengue is endemic but demonstrating insufficient efficacy in immunologically naive populations. Since virus-neutralizing antibodies do not invariably correlate with vaccine efficacy, other markers that may predict protection, including cell-mediated immunity, are urgently needed. Previously, the Walter Reed Army Institute of Research developed a monovalent purified inactivated virus (PIV) vaccine candidate against dengue virus serotype 1 (DENV-1) adjuvanted with alum. The PIV vaccine was safe and immunogenic in a phase I dose escalation trial in healthy, flavivirus-naive adults in the United States. From that trial, peripheral blood mononuclear cells obtained at various time points pre- and postvaccination were used to measure DENV-1-specific T cell responses. After vaccination, a predominant CD4+ T cell-mediated response to peptide pools covering the DENV-1 structural proteins was observed. Over half (13/20) of the subjects produced interleukin-2 (IL-2) in response to DENV peptides, and the majority (17/20) demonstrated peptide-specific CD4+ T cell proliferation. In addition, analysis of postvaccination cell culture supernatants demonstrated an increased rate of production of cytokines, including gamma interferon (IFN-γ), IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Overall, the vaccine was found to have elicited DENV-specific CD4+ T cell responses as measured by enzyme-linked immunosorbent spot (ELISpot), intracellular cytokine staining (ICS), lymphocyte proliferation, and cytokine production assays. Thus, together with antibody readouts, the use of a multifaceted measurement of cell-mediated immune responses after vaccination is a useful strategy for more comprehensively characterizing immunity generated by dengue vaccines. IMPORTANCE Dengue is a tropical disease transmitted by mosquitoes, and nearly half of the world’s population lives in areas where individuals are at risk of infection. Several vaccines for dengue are in development, including one which was recently licensed in several countries, although its utility is limited to people who have already been infected with one of the four dengue viruses. One major hurdle to understanding whether a dengue vaccine will work for everyone—before exposure—is the necessity of knowing which marker can be measured in the blood to signal that the individual has protective immunity. This report describes an approach measuring multiple different parts of immunity in order to characterize which signals one candidate vaccine imparted to a small number of human volunteers. This approach was designed to be able to be applied to any dengue vaccine study so that the data can be compared and used to inform future vaccine design and/or optimization strategies.Heather FribergLuis J. MartinezLeyi LinJason M. BlaylockRafael A. De La BarreraAlan L. RothmanJ. Robert PutnakKenneth H. EckelsStephen J. ThomasRichard G. JarmanJeffrey R. CurrierAmerican Society for MicrobiologyarticleCMIPIVT cellsdenguevaccineMicrobiologyQR1-502ENmSphere, Vol 5, Iss 1 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	CMI PIV T cells dengue vaccine Microbiology QR1-502
spellingShingle	CMI PIV T cells dengue vaccine Microbiology QR1-502 Heather Friberg Luis J. Martinez Leyi Lin Jason M. Blaylock Rafael A. De La Barrera Alan L. Rothman J. Robert Putnak Kenneth H. Eckels Stephen J. Thomas Richard G. Jarman Jeffrey R. Currier Cell-Mediated Immunity Generated in Response to a Purified Inactivated Vaccine for Dengue Virus Type 1
description	ABSTRACT Dengue is the most prevalent arboviral disease afflicting humans, and a vaccine appears to be the most rational means of control. Dengue vaccine development is in a critical phase, with the first vaccine licensed in some countries where dengue is endemic but demonstrating insufficient efficacy in immunologically naive populations. Since virus-neutralizing antibodies do not invariably correlate with vaccine efficacy, other markers that may predict protection, including cell-mediated immunity, are urgently needed. Previously, the Walter Reed Army Institute of Research developed a monovalent purified inactivated virus (PIV) vaccine candidate against dengue virus serotype 1 (DENV-1) adjuvanted with alum. The PIV vaccine was safe and immunogenic in a phase I dose escalation trial in healthy, flavivirus-naive adults in the United States. From that trial, peripheral blood mononuclear cells obtained at various time points pre- and postvaccination were used to measure DENV-1-specific T cell responses. After vaccination, a predominant CD4+ T cell-mediated response to peptide pools covering the DENV-1 structural proteins was observed. Over half (13/20) of the subjects produced interleukin-2 (IL-2) in response to DENV peptides, and the majority (17/20) demonstrated peptide-specific CD4+ T cell proliferation. In addition, analysis of postvaccination cell culture supernatants demonstrated an increased rate of production of cytokines, including gamma interferon (IFN-γ), IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Overall, the vaccine was found to have elicited DENV-specific CD4+ T cell responses as measured by enzyme-linked immunosorbent spot (ELISpot), intracellular cytokine staining (ICS), lymphocyte proliferation, and cytokine production assays. Thus, together with antibody readouts, the use of a multifaceted measurement of cell-mediated immune responses after vaccination is a useful strategy for more comprehensively characterizing immunity generated by dengue vaccines. IMPORTANCE Dengue is a tropical disease transmitted by mosquitoes, and nearly half of the world’s population lives in areas where individuals are at risk of infection. Several vaccines for dengue are in development, including one which was recently licensed in several countries, although its utility is limited to people who have already been infected with one of the four dengue viruses. One major hurdle to understanding whether a dengue vaccine will work for everyone—before exposure—is the necessity of knowing which marker can be measured in the blood to signal that the individual has protective immunity. This report describes an approach measuring multiple different parts of immunity in order to characterize which signals one candidate vaccine imparted to a small number of human volunteers. This approach was designed to be able to be applied to any dengue vaccine study so that the data can be compared and used to inform future vaccine design and/or optimization strategies.
format	article
author	Heather Friberg Luis J. Martinez Leyi Lin Jason M. Blaylock Rafael A. De La Barrera Alan L. Rothman J. Robert Putnak Kenneth H. Eckels Stephen J. Thomas Richard G. Jarman Jeffrey R. Currier
author_facet	Heather Friberg Luis J. Martinez Leyi Lin Jason M. Blaylock Rafael A. De La Barrera Alan L. Rothman J. Robert Putnak Kenneth H. Eckels Stephen J. Thomas Richard G. Jarman Jeffrey R. Currier
author_sort	Heather Friberg
title	Cell-Mediated Immunity Generated in Response to a Purified Inactivated Vaccine for Dengue Virus Type 1
title_short	Cell-Mediated Immunity Generated in Response to a Purified Inactivated Vaccine for Dengue Virus Type 1
title_full	Cell-Mediated Immunity Generated in Response to a Purified Inactivated Vaccine for Dengue Virus Type 1
title_fullStr	Cell-Mediated Immunity Generated in Response to a Purified Inactivated Vaccine for Dengue Virus Type 1
title_full_unstemmed	Cell-Mediated Immunity Generated in Response to a Purified Inactivated Vaccine for Dengue Virus Type 1
title_sort	cell-mediated immunity generated in response to a purified inactivated vaccine for dengue virus type 1
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/9a70ddf949f2464fbfa4032091e25a8f
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Cell-Mediated Immunity Generated in Response to a Purified Inactivated Vaccine for Dengue Virus Type 1

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