Enhanced dengue vaccine virus replication and neutralizing antibody responses in immune primed rhesus macaques

Abstract Antibody-dependent enhancement (ADE) is suspected to influence dengue virus (DENV) infection, but the role ADE plays in vaccination strategies incorporating live attenuated virus components is less clear. Using a heterologous prime-boost strategy in rhesus macaques, we examine the effect of...

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Autores principales: Michael K. McCracken, Caitlin H. Kuklis, Chandrika B. Kannadka, David A. Barvir, Mark A. Sanborn, Adam T. Waickman, Hayden C. Siegfried, Kaitlin A. Victor, Kristin L. Hatch, Rafael De La Barrera, Shannon D. Walls, Wiriya Rutvisuttinunt, Jeffrey R. Currier, Heather Friberg, Richard G. Jarman, Gregory D. Gromowski
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:d8ee938ae9d948e0b132ccac35634eaa2021-12-02T15:45:20ZEnhanced dengue vaccine virus replication and neutralizing antibody responses in immune primed rhesus macaques10.1038/s41541-021-00339-y2059-0105https://doaj.org/article/d8ee938ae9d948e0b132ccac35634eaa2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00339-yhttps://doaj.org/toc/2059-0105Abstract Antibody-dependent enhancement (ADE) is suspected to influence dengue virus (DENV) infection, but the role ADE plays in vaccination strategies incorporating live attenuated virus components is less clear. Using a heterologous prime-boost strategy in rhesus macaques, we examine the effect of priming with DENV purified inactivated vaccines (PIVs) on a tetravalent live attenuated vaccine (LAV). Sera exhibited low-level neutralizing antibodies (NAb) post PIV priming, yet moderate to high in vitro ADE activity. Following LAV administration, the PIV primed groups exhibited DENV-2 LAV peak viremias up to 1,176-fold higher than the mock primed group, and peak viremia correlated with in vitro ADE. Furthermore, PIV primed groups had more balanced and higher DENV-1–4 NAb seroconversion and titers than the mock primed group following LAV administration. These results have implications for the development of effective DENV vaccine prime-boost strategies and for our understanding of the role played by ADE in modulating DENV replication.Michael K. McCrackenCaitlin H. KuklisChandrika B. KannadkaDavid A. BarvirMark A. SanbornAdam T. WaickmanHayden C. SiegfriedKaitlin A. VictorKristin L. HatchRafael De La BarreraShannon D. WallsWiriya RutvisuttinuntJeffrey R. CurrierHeather FribergRichard G. JarmanGregory D. GromowskiNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Immunologic diseases. Allergy
RC581-607
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle Immunologic diseases. Allergy
RC581-607
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Michael K. McCracken
Caitlin H. Kuklis
Chandrika B. Kannadka
David A. Barvir
Mark A. Sanborn
Adam T. Waickman
Hayden C. Siegfried
Kaitlin A. Victor
Kristin L. Hatch
Rafael De La Barrera
Shannon D. Walls
Wiriya Rutvisuttinunt
Jeffrey R. Currier
Heather Friberg
Richard G. Jarman
Gregory D. Gromowski
Enhanced dengue vaccine virus replication and neutralizing antibody responses in immune primed rhesus macaques
description Abstract Antibody-dependent enhancement (ADE) is suspected to influence dengue virus (DENV) infection, but the role ADE plays in vaccination strategies incorporating live attenuated virus components is less clear. Using a heterologous prime-boost strategy in rhesus macaques, we examine the effect of priming with DENV purified inactivated vaccines (PIVs) on a tetravalent live attenuated vaccine (LAV). Sera exhibited low-level neutralizing antibodies (NAb) post PIV priming, yet moderate to high in vitro ADE activity. Following LAV administration, the PIV primed groups exhibited DENV-2 LAV peak viremias up to 1,176-fold higher than the mock primed group, and peak viremia correlated with in vitro ADE. Furthermore, PIV primed groups had more balanced and higher DENV-1–4 NAb seroconversion and titers than the mock primed group following LAV administration. These results have implications for the development of effective DENV vaccine prime-boost strategies and for our understanding of the role played by ADE in modulating DENV replication.
format article
author Michael K. McCracken
Caitlin H. Kuklis
Chandrika B. Kannadka
David A. Barvir
Mark A. Sanborn
Adam T. Waickman
Hayden C. Siegfried
Kaitlin A. Victor
Kristin L. Hatch
Rafael De La Barrera
Shannon D. Walls
Wiriya Rutvisuttinunt
Jeffrey R. Currier
Heather Friberg
Richard G. Jarman
Gregory D. Gromowski
author_facet Michael K. McCracken
Caitlin H. Kuklis
Chandrika B. Kannadka
David A. Barvir
Mark A. Sanborn
Adam T. Waickman
Hayden C. Siegfried
Kaitlin A. Victor
Kristin L. Hatch
Rafael De La Barrera
Shannon D. Walls
Wiriya Rutvisuttinunt
Jeffrey R. Currier
Heather Friberg
Richard G. Jarman
Gregory D. Gromowski
author_sort Michael K. McCracken
title Enhanced dengue vaccine virus replication and neutralizing antibody responses in immune primed rhesus macaques
title_short Enhanced dengue vaccine virus replication and neutralizing antibody responses in immune primed rhesus macaques
title_full Enhanced dengue vaccine virus replication and neutralizing antibody responses in immune primed rhesus macaques
title_fullStr Enhanced dengue vaccine virus replication and neutralizing antibody responses in immune primed rhesus macaques
title_full_unstemmed Enhanced dengue vaccine virus replication and neutralizing antibody responses in immune primed rhesus macaques
title_sort enhanced dengue vaccine virus replication and neutralizing antibody responses in immune primed rhesus macaques
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/d8ee938ae9d948e0b132ccac35634eaa
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