Dataset Information

Zika Virus Tissue and Blood Compartmentalization in Acute Infection of Rhesus Macaques.

ABSTRACT: Animal models of Zika virus (ZIKV) are needed to better understand tropism and pathogenesis and to test candidate vaccines and therapies to curtail the pandemic. Humans and rhesus macaques possess similar fetal development and placental biology that is not shared between humans and rodents. We inoculated 2 non-pregnant rhesus macaques with a 2015 Brazilian ZIKV strain. Consistent with most human infections, the animals experienced no clinical disease but developed short-lived plasma viremias that cleared as neutralizing antibody developed. In 1 animal, viral RNA (vRNA) could be detected longer in whole blood than in plasma. Despite no major histopathologic changes, many adult tissues contained vRNA 14 days post-infection with highest levels in hemolymphatic tissues. These observations warrant further studies to investigate ZIKV persistence and its potential clinical implications for transmission via blood products or tissue and organ transplants.

SUBMITTER: Coffey LL

PROVIDER: S-EPMC5283740 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Zika Virus Tissue and Blood Compartmentalization in Acute Infection of Rhesus Macaques.

Coffey Lark L LL Pesavento Patricia A PA Keesler Rebekah I RI Singapuri Anil A Watanabe Jennifer J Watanabe Rie R Yee JoAnn J Bliss-Moreau Eliza E Cruzen Christina C Christe Kari L KL Reader J Rachel JR von Morgenland Wilhelm W Gibbons Anne M AM Allen A Mark AM Linnen Jeff J Gao Kui K Delwart Eric E Simmons Graham G Stone Mars M Lanteri Marion M Bakkour Sonia S Busch Michael M Morrison John J Van Rompay Koen K A KK

PloS one 20170131 1

Animal models of Zika virus (ZIKV) are needed to better understand tropism and pathogenesis and to test candidate vaccines and therapies to curtail the pandemic. Humans and rhesus macaques possess similar fetal development and placental biology that is not shared between humans and rodents. We inoculated 2 non-pregnant rhesus macaques with a 2015 Brazilian ZIKV strain. Consistent with most human infections, the animals experienced no clinical disease but developed short-lived plasma viremias tha ...[more]

PMID: 28141843

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Project description:BackgroundZika virus (ZIKV), a mosquito-borne flavivirus, is a re-emerging virus that constitutes a public health threat due to its recent global spread, recurrent outbreaks, and infections that are associated with neurological abnormalities in developing fetuses and Guillain-Barré syndrome in adults. To date, there are no approved vaccines against ZIKV infection. Various preclinical and clinical development programs are currently ongoing in an effort to bring forward a vaccine for ZIKV.Methodology/principle findingsWe have developed a ZIKV vaccine candidate based on Virus-Like-Particles (VLPs) produced in HEK293 mammalian cells using the prM (a precursor to M protein) and envelope (E) structural protein genes from ZIKV. Transient transfection of cells via plasmid and electroporation produced VLPs which were subsequently purified by column chromatography yielding approximately 2mg/L. Initially, immunogenicity and efficacy were evaluated in AG129 mice using a dose titration of VLP with and without Alhydrogel 2% (alum) adjuvant. We found that VLP with and without alum elicited ZIKV-specific serum neutralizing antibodies (nAbs) and that titers correlated with protection. A follow-up immunogenicity and efficacy study in rhesus macaques was performed using VLP formulated with alum. Multiple neutralization assay methods were performed on immune sera including a plaque reduction neutralization test, a microneutralization assay, and a Zika virus Renilla luciferase neutralization assay. All of these assays indicate that following immunization, VLP induces high titer nAbs which correlate with protection against ZIKV challenge.Conclusions/significanceThese studies confirm that ZIKV VLPs could be efficiently generated and purified. Upon VLP immunization, in both mice and NHPs, nAb was induced that correlate with protection against ZIKV challenge. These studies support translational efforts in developing a ZIKV VLP vaccine for evaluation in human clinical trials.

Dataset Information

Zika Virus Tissue and Blood Compartmentalization in Acute Infection of Rhesus Macaques.

Publications

Zika Virus Tissue and Blood Compartmentalization in Acute Infection of Rhesus Macaques.

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