Zika Virus-Immune Plasmas from Symptomatic and Asymptomatic Individuals Enhance Zika Pathogenesis in Adult and Pregnant Mice

Byoung Shik Shim, Young Chan Kwon, Michael J. Ricciardi, Mars Stone, Yuka Otsuka, Fatma Berri, Jaclyn M. Kwal, Diogo M. Magnani, Cody B. Jackson, Audrey S. Richard, Philip Norris, Michael Busch, Christine L. Curry, Michael Farzan, David Watkins, Hyeryun Choe

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Preexisting immunity against dengue virus or West Nile virus was previously reported to mediate antibody-dependent enhancement (ADE) of Zika virus (ZIKV) infection in a mouse model. We show here that ZIKV-immune plasma samples from both symptomatic and asymptomatic individuals mediated ZIKV ADE of infection in vitro and in mice. In a lethal infection model with a viral inoculum 10 times higher, both ADE and protection were observed, depending on the amount of infused immune plasma. In a vertical-transmission model, ZIKV-immune plasma infused to timed pregnant mice increased fetal demise and decreased the body weight of surviving fetuses. Depletion of IgG from an immune plasma abolished ADE of infection, and the presence of purified IgG alone mediated ADE of infection. Higher viral loads and proinflammatory cytokines were detected in mice treated with ZIKV-immune plasma samples compared to those receiving control plasma. Together, these data show that passive immunization with homotypic ZIKV antibodies, depending on the concentration, could either worsen or limit a subsequent ZIKV infection.IMPORTANCE Antibody-dependent enhancement (ADE) of virus infection is common to many viruses and is problematic when plasma antibody levels decline to subneutralizing concentrations. ADE of infection is especially important among flaviviruses, many of which are the cause of global health problems. Recently, human plasma samples immune to heterologous flaviviruses were shown to promote Zika virus (ZIKV) infection. Here we showed in immunocompromised mouse models that homologous immune plasma samples protect mice from subsequent infection at high antibody concentrations but that they mediate ADE of infection and increase ZIKV pathogenesis in adult mice and fetal demise during pregnancy at low concentrations.

Original languageEnglish (US)
JournalmBio
Volume10
Issue number4
DOIs
StatePublished - Jul 2 2019

Fingerprint

Antibody-Dependent Enhancement
Infection
Flavivirus
Fetal Death
Antibodies
Immunoglobulin G
Zika Virus
West Nile virus
Dengue Virus
Passive Immunization
Virus Diseases
Viral Load
Immunity
Fetus
Body Weight
Cytokines
Viruses

Keywords

  • antibody-dependent enhancement
  • congenital disease
  • homotypic
  • microcephaly
  • pregnancy
  • vaccine
  • viral pathogenesis
  • Zika virus

ASJC Scopus subject areas

  • Microbiology
  • Virology

Cite this

Shim, B. S., Kwon, Y. C., Ricciardi, M. J., Stone, M., Otsuka, Y., Berri, F., ... Choe, H. (2019). Zika Virus-Immune Plasmas from Symptomatic and Asymptomatic Individuals Enhance Zika Pathogenesis in Adult and Pregnant Mice. mBio, 10(4). https://doi.org/10.1128/mBio.00758-19

Zika Virus-Immune Plasmas from Symptomatic and Asymptomatic Individuals Enhance Zika Pathogenesis in Adult and Pregnant Mice. / Shim, Byoung Shik; Kwon, Young Chan; Ricciardi, Michael J.; Stone, Mars; Otsuka, Yuka; Berri, Fatma; Kwal, Jaclyn M.; Magnani, Diogo M.; Jackson, Cody B.; Richard, Audrey S.; Norris, Philip; Busch, Michael; Curry, Christine L.; Farzan, Michael; Watkins, David; Choe, Hyeryun.

In: mBio, Vol. 10, No. 4, 02.07.2019.

Research output: Contribution to journalArticle

Shim, BS, Kwon, YC, Ricciardi, MJ, Stone, M, Otsuka, Y, Berri, F, Kwal, JM, Magnani, DM, Jackson, CB, Richard, AS, Norris, P, Busch, M, Curry, CL, Farzan, M, Watkins, D & Choe, H 2019, 'Zika Virus-Immune Plasmas from Symptomatic and Asymptomatic Individuals Enhance Zika Pathogenesis in Adult and Pregnant Mice', mBio, vol. 10, no. 4. https://doi.org/10.1128/mBio.00758-19
Shim, Byoung Shik ; Kwon, Young Chan ; Ricciardi, Michael J. ; Stone, Mars ; Otsuka, Yuka ; Berri, Fatma ; Kwal, Jaclyn M. ; Magnani, Diogo M. ; Jackson, Cody B. ; Richard, Audrey S. ; Norris, Philip ; Busch, Michael ; Curry, Christine L. ; Farzan, Michael ; Watkins, David ; Choe, Hyeryun. / Zika Virus-Immune Plasmas from Symptomatic and Asymptomatic Individuals Enhance Zika Pathogenesis in Adult and Pregnant Mice. In: mBio. 2019 ; Vol. 10, No. 4.
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abstract = "Preexisting immunity against dengue virus or West Nile virus was previously reported to mediate antibody-dependent enhancement (ADE) of Zika virus (ZIKV) infection in a mouse model. We show here that ZIKV-immune plasma samples from both symptomatic and asymptomatic individuals mediated ZIKV ADE of infection in vitro and in mice. In a lethal infection model with a viral inoculum 10 times higher, both ADE and protection were observed, depending on the amount of infused immune plasma. In a vertical-transmission model, ZIKV-immune plasma infused to timed pregnant mice increased fetal demise and decreased the body weight of surviving fetuses. Depletion of IgG from an immune plasma abolished ADE of infection, and the presence of purified IgG alone mediated ADE of infection. Higher viral loads and proinflammatory cytokines were detected in mice treated with ZIKV-immune plasma samples compared to those receiving control plasma. Together, these data show that passive immunization with homotypic ZIKV antibodies, depending on the concentration, could either worsen or limit a subsequent ZIKV infection.IMPORTANCE Antibody-dependent enhancement (ADE) of virus infection is common to many viruses and is problematic when plasma antibody levels decline to subneutralizing concentrations. ADE of infection is especially important among flaviviruses, many of which are the cause of global health problems. Recently, human plasma samples immune to heterologous flaviviruses were shown to promote Zika virus (ZIKV) infection. Here we showed in immunocompromised mouse models that homologous immune plasma samples protect mice from subsequent infection at high antibody concentrations but that they mediate ADE of infection and increase ZIKV pathogenesis in adult mice and fetal demise during pregnancy at low concentrations.",
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