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...
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Published in | Frontiers in immunology Vol. 5; p. 263 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
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05.06.2014
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Abstract | 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 tetravalent dengue 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 delivery devices (PharmaJet) in non-human primates. 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 (2 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. |
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AbstractList | 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. 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 tetravalent dengue 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 delivery devices (PharmaJet) in non-human primates. 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 (2 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. 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 tetravalent dengue 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 delivery devices (PharmaJet) in non-human primates. 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 (2 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. |
Author | Haller, Aurelia A Capuano, Saverio Stinchcomb, Dan T Paykel, Joanna Royals, Michael Rakasz, Eva G Huang, Claire Y-H Ambuel, Yuping Brewoo, Joseph N Osorio, Jorge E Partidos, Charalambos D Young, Ginger Weisgrau, Kim L |
AuthorAffiliation | 1 Takeda Vaccines, Inc. , Madison, WI , USA 4 PharmaJet Inc. , Golden, CO , USA 5 Division of Vector-Borne Diseases, Centers for Disease Control and Prevention , Ft. Collins, CO , USA 2 Wisconsin National Primate Research Center, University of Wisconsin-Madison , Madison, WI , USA 3 Takeda Vaccines, Inc. , Ft Collins, CO , USA |
AuthorAffiliation_xml | – name: 2 Wisconsin National Primate Research Center, University of Wisconsin-Madison , Madison, WI , USA – name: 4 PharmaJet Inc. , Golden, CO , USA – name: 5 Division of Vector-Borne Diseases, Centers for Disease Control and Prevention , Ft. Collins, CO , USA – name: 1 Takeda Vaccines, Inc. , Madison, WI , USA – name: 3 Takeda Vaccines, Inc. , Ft Collins, CO , USA |
Author_xml | – sequence: 1 givenname: Yuping surname: Ambuel fullname: Ambuel, Yuping organization: Takeda Vaccines, Inc. , Madison, WI , USA – sequence: 2 givenname: Ginger surname: Young fullname: Young, Ginger organization: Takeda Vaccines, Inc. , Madison, WI , USA – sequence: 3 givenname: Joseph N surname: Brewoo fullname: Brewoo, Joseph N organization: Takeda Vaccines, Inc. , Madison, WI , USA – sequence: 4 givenname: Joanna surname: Paykel fullname: Paykel, Joanna organization: Takeda Vaccines, Inc. , Madison, WI , USA – sequence: 5 givenname: Kim L surname: Weisgrau fullname: Weisgrau, Kim L organization: Wisconsin National Primate Research Center, University of Wisconsin-Madison , Madison, WI , USA – sequence: 6 givenname: Eva G surname: Rakasz fullname: Rakasz, Eva G organization: Wisconsin National Primate Research Center, University of Wisconsin-Madison , Madison, WI , USA – sequence: 7 givenname: Aurelia A surname: Haller fullname: Haller, Aurelia A organization: Takeda Vaccines, Inc. , Ft Collins, CO , USA – sequence: 8 givenname: Michael surname: Royals fullname: Royals, Michael organization: PharmaJet Inc. , Golden, CO , USA – sequence: 9 givenname: Claire Y-H surname: Huang fullname: Huang, Claire Y-H organization: Division of Vector-Borne Diseases, Centers for Disease Control and Prevention , Ft. Collins, CO , USA – sequence: 10 givenname: Saverio surname: Capuano fullname: Capuano, Saverio organization: Wisconsin National Primate Research Center, University of Wisconsin-Madison , Madison, WI , USA – sequence: 11 givenname: Dan T surname: Stinchcomb fullname: Stinchcomb, Dan T organization: Takeda Vaccines, Inc. , Ft Collins, CO , USA – sequence: 12 givenname: Charalambos D surname: Partidos fullname: Partidos, Charalambos D organization: Takeda Vaccines, Inc. , Madison, WI , USA – sequence: 13 givenname: Jorge E surname: Osorio fullname: Osorio, Jorge E organization: Takeda Vaccines, Inc. , Madison, WI , USA |
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Keywords | neutralizing antibodies vaccine needle-free delivery dengue T cell responses non-human primates |
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Snippet | Dengue viruses (DENVs) cause approximately 390 million cases of DENV infections annually and over 3 billion people worldwide are at risk of infection. No... |
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SubjectTerms | Dengue Immunology needle-free delivery neutralizing antibodies non-human primates T cell responses Vaccine |
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Title | A rapid immunization strategy with a live-attenuated tetravalent dengue vaccine elicits protective neutralizing antibody responses in non-human primates |
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