A rapid immunization strategy with a live attenuated tetravalent dengue vaccine elicits protective neutralizing antibody responses in non-human primates
Dengue viruses (DENVs) cause approximately 390 million cases of DENV infections annually and over 3 billion people worldwide are at risk of infection. No dengue vaccine is currently available nor is there an antiviral therapy for DENV infections. We have developed a tetravalent live-attenuated DENV...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-06-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00263/full |
| _version_ | 1811242754609512448 |
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| author | Yuping eAmbuel Ginger eYoung Joseph eBrewoo Joanna ePaykel Kim eWeisgrau Eva eRakasz Aurelia eHaller Michael eRoyals Claire eHuang Saverio eCapuono Dan eStinchcomb Charalambos ePartidos Jorge eOsorio |
| author_facet | Yuping eAmbuel Ginger eYoung Joseph eBrewoo Joanna ePaykel Kim eWeisgrau Eva eRakasz Aurelia eHaller Michael eRoyals Claire eHuang Saverio eCapuono Dan eStinchcomb Charalambos ePartidos Jorge eOsorio |
| author_sort | Yuping eAmbuel |
| collection | DOAJ |
| description | Dengue viruses (DENVs) cause approximately 390 million cases of DENV infections annually and over 3 billion people worldwide are at risk of infection. No dengue vaccine is currently available nor is there an antiviral therapy for DENV infections. We have developed a tetravalent live-attenuated DENV vaccine (TDV) that consists of a molecularly characterized attenuated DENV-2 strain (TDV-2) and three chimeric viruses containing the pre-membrane and envelope genes of DENV-1, -3 and -4 expressed in the context of the TDV-2 genome. To impact dengue vaccine delivery in endemic areas and immunize travelers, a simple and rapid immunization strategy (RIS) is preferred. We investigated RIS consisting of two full vaccine doses being administered subcutaneously or intradermally on the initial vaccination visit (day 0) at two different anatomical locations with a needle-free disposable syringe jet injection (DSJI) delivery devices (PharmaJet) in non-human primates (NHP). This vaccination strategy resulted in efficient priming and induction of neutralizing antibody responses to all four DENV serotypes comparable to those elicited by the traditional prime and boost (two months later) vaccination schedule. In addition, the vaccine induced CD4+ and CD8+ T cells producing IFN-γ, IL-2, and TNF-α, and targeting the DENV-2 NS1, NS3 and NS5 proteins. Moreover, vaccine-specific T cells were cross-reactive with the non-structural NS3 and NS5 proteins of DENV-4. When animals were challenged with DENV-2 they were protected with no detectable viremia, and exhibited sterilizing immunity (no increase of neutralizing titers post- challenge). RIS could decrease vaccination visits and provide quick immune response to all four DENV serotypes. This strategy could increase vaccination compliance and would be especially advantageous for travelers into endemic areas. |
| first_indexed | 2024-04-12T13:56:51Z |
| format | Article |
| id | doaj.art-4ce0be11586c4b08a660a116f504491d |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T13:56:51Z |
| publishDate | 2014-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-4ce0be11586c4b08a660a116f504491d2022-12-22T03:30:21ZengFrontiers Media S.A.Frontiers in Immunology1664-32242014-06-01510.3389/fimmu.2014.0026391031A rapid immunization strategy with a live attenuated tetravalent dengue vaccine elicits protective neutralizing antibody responses in non-human primatesYuping eAmbuel0Ginger eYoung1Joseph eBrewoo2Joanna ePaykel3Kim eWeisgrau4Eva eRakasz5Aurelia eHaller6Michael eRoyals7Claire eHuang8Saverio eCapuono9Dan eStinchcomb10Charalambos ePartidos11Jorge eOsorio12Takeda Vacines, Inc. MadisonTakeda Vacines, Inc. MadisonTakeda Vacines, Inc. MadisonTakeda Vacines, Inc. MadisonUniversity of Wisconsin-MadisonUniversity of Wisconsin-MadisonTakeda Vaccines, Inc. Fort CollinsPharmaJet, IncCenters for disease control and preventionUniversity of Wisconsin-MadisonTakeda Vaccines, Inc. Fort CollinsTakeda Vacines, Inc. MadisonTakeda Vacines, Inc. MadisonDengue viruses (DENVs) cause approximately 390 million cases of DENV infections annually and over 3 billion people worldwide are at risk of infection. No dengue vaccine is currently available nor is there an antiviral therapy for DENV infections. We have developed a tetravalent live-attenuated DENV vaccine (TDV) that consists of a molecularly characterized attenuated DENV-2 strain (TDV-2) and three chimeric viruses containing the pre-membrane and envelope genes of DENV-1, -3 and -4 expressed in the context of the TDV-2 genome. To impact dengue vaccine delivery in endemic areas and immunize travelers, a simple and rapid immunization strategy (RIS) is preferred. We investigated RIS consisting of two full vaccine doses being administered subcutaneously or intradermally on the initial vaccination visit (day 0) at two different anatomical locations with a needle-free disposable syringe jet injection (DSJI) delivery devices (PharmaJet) in non-human primates (NHP). This vaccination strategy resulted in efficient priming and induction of neutralizing antibody responses to all four DENV serotypes comparable to those elicited by the traditional prime and boost (two months later) vaccination schedule. In addition, the vaccine induced CD4+ and CD8+ T cells producing IFN-γ, IL-2, and TNF-α, and targeting the DENV-2 NS1, NS3 and NS5 proteins. Moreover, vaccine-specific T cells were cross-reactive with the non-structural NS3 and NS5 proteins of DENV-4. When animals were challenged with DENV-2 they were protected with no detectable viremia, and exhibited sterilizing immunity (no increase of neutralizing titers post- challenge). RIS could decrease vaccination visits and provide quick immune response to all four DENV serotypes. This strategy could increase vaccination compliance and would be especially advantageous for travelers into endemic areas.http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00263/fullDengueVaccinenon-human primatesneutralizing antibodiesT cell responsesneedle-free delivery |
| spellingShingle | Yuping eAmbuel Ginger eYoung Joseph eBrewoo Joanna ePaykel Kim eWeisgrau Eva eRakasz Aurelia eHaller Michael eRoyals Claire eHuang Saverio eCapuono Dan eStinchcomb Charalambos ePartidos Jorge eOsorio A rapid immunization strategy with a live attenuated tetravalent dengue vaccine elicits protective neutralizing antibody responses in non-human primates Frontiers in Immunology Dengue Vaccine non-human primates neutralizing antibodies T cell responses needle-free delivery |
| title | A rapid immunization strategy with a live attenuated tetravalent dengue vaccine elicits protective neutralizing antibody responses in non-human primates |
| title_full | A rapid immunization strategy with a live attenuated tetravalent dengue vaccine elicits protective neutralizing antibody responses in non-human primates |
| title_fullStr | A rapid immunization strategy with a live attenuated tetravalent dengue vaccine elicits protective neutralizing antibody responses in non-human primates |
| title_full_unstemmed | A rapid immunization strategy with a live attenuated tetravalent dengue vaccine elicits protective neutralizing antibody responses in non-human primates |
| title_short | A rapid immunization strategy with a live attenuated tetravalent dengue vaccine elicits protective neutralizing antibody responses in non-human primates |
| title_sort | rapid immunization strategy with a live attenuated tetravalent dengue vaccine elicits protective neutralizing antibody responses in non human primates |
| topic | Dengue Vaccine non-human primates neutralizing antibodies T cell responses needle-free delivery |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00263/full |
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