Impact of prior Dengue immunity on Zika vaccine protection in rhesus macaques and mice

Rafael A. Larocca; Peter Abbink; John D. Ventura; Abishek Chandrashekar; Noe Mercado; Zhenfeng Li; Erica Borducchi; Rafael A. de la Barrera; Kenneth H. Eckels; Kayvon Modjarrad; Michael P. Busch; Nelson L. Michael; Dan H. Barouch

doi:10.1371/journal.ppat.1009673

Impact of prior Dengue immunity on Zika vaccine protection in rhesus macaques and mice

Rafael A. Larocca, Peter Abbink, John D. Ventura, Abishek Chandrashekar, Noe Mercado, Zhenfeng Li, Erica Borducchi, Rafael A. de la Barrera, Kenneth H. Eckels, Kayvon Modjarrad, Michael P. Busch, Nelson L. Michael, Dan H. Barouch^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Pre-existing immunity to flaviviruses can influence the outcome of subsequent flavivirus infections. Therefore, it is critical to determine whether baseline DENV immunity may influence subsequent ZIKV infection and the protective efficacy of ZIKV vaccines. In this study, we investigated the impact of pre-existing DENV immunity induced by vaccination on ZIKV infection and the protective efficacy of an inactivated ZIKV vaccine. Rhesus macaques and mice inoculated with a live attenuated DENV vaccine developed neutralizing antibodies (NAbs) to multiple DENV serotypes but no cross-reactive NAbs responses to ZIKV. Animals with baseline DENV NAbs did not exhibit enhanced ZIKV infection and showed no overall reduction in ZIKV vaccine protection. Moreover, passive transfer of purified DENV-specific IgG from convalescent human donors did not augment ZIKV infection in STAT2 ^-/- and BALB/c mice. In summary, these results suggest that baseline DENV immunity induced by vaccination does not significantly enhance ZIKV infection or impair the protective efficacy of candidate ZIKV vaccines in these models. These data can help inform immunization strategies in regions of the world with multiple circulating pathogenic flaviviruses.

Original language	English
Article number	e1009673
Journal	PLoS Pathogens
Volume	17
Issue number	6
DOIs	https://doi.org/10.1371/journal.ppat.1009673
State	Published - Jun 2021
Externally published	Yes

Access to Document

10.1371/journal.ppat.1009673

Cite this

Larocca, R. A., Abbink, P., Ventura, J. D., Chandrashekar, A., Mercado, N., Li, Z., Borducchi, E., de la Barrera, R. A., Eckels, K. H., Modjarrad, K., Busch, M. P., Michael, N. L., & Barouch, D. H. (2021). Impact of prior Dengue immunity on Zika vaccine protection in rhesus macaques and mice. PLoS Pathogens, 17(6), Article e1009673. https://doi.org/10.1371/journal.ppat.1009673

@article{8926bcfc9e4f482a987113e6e2a1bf01,

title = "Impact of prior Dengue immunity on Zika vaccine protection in rhesus macaques and mice",

abstract = "Pre-existing immunity to flaviviruses can influence the outcome of subsequent flavivirus infections. Therefore, it is critical to determine whether baseline DENV immunity may influence subsequent ZIKV infection and the protective efficacy of ZIKV vaccines. In this study, we investigated the impact of pre-existing DENV immunity induced by vaccination on ZIKV infection and the protective efficacy of an inactivated ZIKV vaccine. Rhesus macaques and mice inoculated with a live attenuated DENV vaccine developed neutralizing antibodies (NAbs) to multiple DENV serotypes but no cross-reactive NAbs responses to ZIKV. Animals with baseline DENV NAbs did not exhibit enhanced ZIKV infection and showed no overall reduction in ZIKV vaccine protection. Moreover, passive transfer of purified DENV-specific IgG from convalescent human donors did not augment ZIKV infection in STAT2 -/- and BALB/c mice. In summary, these results suggest that baseline DENV immunity induced by vaccination does not significantly enhance ZIKV infection or impair the protective efficacy of candidate ZIKV vaccines in these models. These data can help inform immunization strategies in regions of the world with multiple circulating pathogenic flaviviruses.",

author = "Larocca, {Rafael A.} and Peter Abbink and Ventura, {John D.} and Abishek Chandrashekar and Noe Mercado and Zhenfeng Li and Erica Borducchi and {de la Barrera}, {Rafael A.} and Eckels, {Kenneth H.} and Kayvon Modjarrad and Busch, {Michael P.} and Michael, {Nelson L.} and Barouch, {Dan H.}",

note = "Publisher Copyright: Copyright: {\textcopyright} 2021 Larocca et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2021",

month = jun,

doi = "10.1371/journal.ppat.1009673",

language = "English",

volume = "17",

journal = "PLoS Pathogens",

issn = "1553-7366",

number = "6",

}

TY - JOUR

T1 - Impact of prior Dengue immunity on Zika vaccine protection in rhesus macaques and mice

AU - Larocca, Rafael A.

AU - Abbink, Peter

AU - Ventura, John D.

AU - Chandrashekar, Abishek

AU - Mercado, Noe

AU - Li, Zhenfeng

AU - Borducchi, Erica

AU - de la Barrera, Rafael A.

AU - Eckels, Kenneth H.

AU - Modjarrad, Kayvon

AU - Busch, Michael P.

AU - Michael, Nelson L.

AU - Barouch, Dan H.

N1 - Publisher Copyright: Copyright: © 2021 Larocca et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2021/6

Y1 - 2021/6

N2 - Pre-existing immunity to flaviviruses can influence the outcome of subsequent flavivirus infections. Therefore, it is critical to determine whether baseline DENV immunity may influence subsequent ZIKV infection and the protective efficacy of ZIKV vaccines. In this study, we investigated the impact of pre-existing DENV immunity induced by vaccination on ZIKV infection and the protective efficacy of an inactivated ZIKV vaccine. Rhesus macaques and mice inoculated with a live attenuated DENV vaccine developed neutralizing antibodies (NAbs) to multiple DENV serotypes but no cross-reactive NAbs responses to ZIKV. Animals with baseline DENV NAbs did not exhibit enhanced ZIKV infection and showed no overall reduction in ZIKV vaccine protection. Moreover, passive transfer of purified DENV-specific IgG from convalescent human donors did not augment ZIKV infection in STAT2 -/- and BALB/c mice. In summary, these results suggest that baseline DENV immunity induced by vaccination does not significantly enhance ZIKV infection or impair the protective efficacy of candidate ZIKV vaccines in these models. These data can help inform immunization strategies in regions of the world with multiple circulating pathogenic flaviviruses.

AB - Pre-existing immunity to flaviviruses can influence the outcome of subsequent flavivirus infections. Therefore, it is critical to determine whether baseline DENV immunity may influence subsequent ZIKV infection and the protective efficacy of ZIKV vaccines. In this study, we investigated the impact of pre-existing DENV immunity induced by vaccination on ZIKV infection and the protective efficacy of an inactivated ZIKV vaccine. Rhesus macaques and mice inoculated with a live attenuated DENV vaccine developed neutralizing antibodies (NAbs) to multiple DENV serotypes but no cross-reactive NAbs responses to ZIKV. Animals with baseline DENV NAbs did not exhibit enhanced ZIKV infection and showed no overall reduction in ZIKV vaccine protection. Moreover, passive transfer of purified DENV-specific IgG from convalescent human donors did not augment ZIKV infection in STAT2 -/- and BALB/c mice. In summary, these results suggest that baseline DENV immunity induced by vaccination does not significantly enhance ZIKV infection or impair the protective efficacy of candidate ZIKV vaccines in these models. These data can help inform immunization strategies in regions of the world with multiple circulating pathogenic flaviviruses.

UR - http://www.scopus.com/inward/record.url?scp=85108910072&partnerID=8YFLogxK

U2 - 10.1371/journal.ppat.1009673

DO - 10.1371/journal.ppat.1009673

M3 - Article

C2 - 34170962

AN - SCOPUS:85108910072

SN - 1553-7366

VL - 17

JO - PLoS Pathogens

JF - PLoS Pathogens

IS - 6

M1 - e1009673

ER -

Impact of prior Dengue immunity on Zika vaccine protection in rhesus macaques and mice

Abstract

Access to Document

Fingerprint

Cite this