2. Academic Validation
  3. Maternally Acquired Zika Antibodies Enhance Dengue Disease Severity in Mice

Maternally Acquired Zika Antibodies Enhance Dengue Disease Severity in Mice

  • Cell Host Microbe. 2018 Nov 14;24(5):743-750.e5. doi: 10.1016/j.chom.2018.09.015.
Angela M Fowler 1,  William W Tang 1,  Matthew P Young 1,  Anila Mamidi 1,  Karla M Viramontes 1,  Melanie D McCauley 1,  Aaron F Carlin 2,  Robert T Schooley 2,  Jesica Swanstrom 3,  Ralph S Baric 3,  Jennifer Govero 4,  Michael S Diamond 4,  Sujan Shresta 5
Affiliations

Affiliations

  • 1 Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
  • 2 Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  • 3 Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA.
  • 4 Departments of Medicine, Molecular Microbiology, Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • 5 Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA; Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: sujan@lji.org.
PMID: 30439343 DOI: 10.1016/j.chom.2018.09.015
Abstract

Antibody (Ab)-dependent enhancement can exacerbate Dengue Virus (DENV) Infection due to cross-reactive Abs from an initial DENV Infection, facilitating replication of a second DENV. Zika virus (ZIKV) emerged in DENV-endemic areas, raising questions about whether existing immunity could affect these related flaviviruses. We show that mice born with circulating maternal Abs against ZIKV develop severe disease upon DENV Infection. Compared with pups of naive mothers, those born to ZIKV-immune mice lacking type I interferon receptor in myeloid cells (LysMCre+IFNAR1fl/fl) exhibit heightened disease and viremia upon DENV Infection. Passive transfer of IgG isolated from mice born to ZIKV-immune mothers resulted in increased viremia in naive recipient mice. Treatment with Abs blocking inflammatory cytokine tumor necrosis factor linked to DENV disease or Abs blocking DENV entry improved survival of DENV-infected mice born to ZIKV-immune mothers. Thus, the maternal Ab response to ZIKV Infection or vaccination might predispose to severe dengue disease in infants.

Keywords

Zika; antibody-dependent enhancement (ADE); dengue; maternal antibody; mouse model; viral pathogenesis.

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