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Microorganisms
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Zika Virus Infection and Immune Response
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Zika Virus Infection and Immune Response

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Molecular Microbiology and Immunology".

Deadline for manuscript submissions: 31 March 2025 | Viewed by 4672

Special Issue Editors

Dr. In-Jeong Kim

E-Mail Website
Guest Editor
Trudeau Institute, Saranac Lake, NY 12983, USA
Interests: viral pathogenesis; vertical transmission; virus–host interaction; host immunity
Dr. Shelton Bradrick

E-Mail Website
Guest Editor
Trudeau Institute, Saranac Lake, NY 12983, USA
Interests: molecular virology; virus-host interaction; flaviviruses; enteroviruses; host immunity

Special Issue Information

Dear Colleagues, 

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that can cause serious illness, including congenital birth defects and Guillain–Barré syndrome during pregnancy. Up until now, there are no licensed effective vaccines or curative antiviral drugs available to treat Zika virus in humans. In immunocompetent adults, Zika virus causes subclinical manifestations with mild symptoms that usually resolve rapidly. However, infections during pregnancy can have devastating effects on the fetus, particularly microcephaly, craniofacial abnormalities, muscle and joint developmental defects, fetal death, and audiovisual abnormalities. 

For this Special Issue, we welcome research on the latest findings on ZIKV infection, including, but not limited to the following areas:

  • sexual transmission;
  • innate immunity in skin and reproductive organs;
  • molecular pathways impacting ZIKV replication and interferon responses;
  • Zika virus infection in pregnancy, virus transmission across the placental and blood–brain barrier, and host immunity during pregnancy, especially at the maternal–fetal interface;
  • interactions between the virus and brain cells;
  • cross-reactive immunity and antibody-mediated enhancement of infection;
  • therapeutic and prophylactic interventions of viral infection;
  • interventions of disease progression;
  • vaccination during pregnancy. 

The aim of this Special issue is to provide a broad overview of current research on ZIKV and the host immune response from molecular to cellular features, which will help to develop better control of viral infection and clinical interventions. 

As Guest Editors of the Special Issue, we cordially invite you to participate. We encourage authors to submit original research articles, review articles, and short communications related to the topic.

Dr. In-Jeong Kim
Dr. Shelton Bradrick
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Microorganisms is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Zika virus
  • virus transmission
  • immunopathogenesis
  • innate and adaptive immunity
  • cross-reactive immunity
  • cross-reactivity
  • pregnancy
  • neurodevelopment
  • vaccine
  • antivirals
 

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Published Papers (4 papers)

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Research

13 pages, 1490 KiB  
Article
Distinct Replication Kinetics, Cytopathogenicity, and Immune Gene Regulation in Human Microglia Cells Infected with Asian and African Lineages of Zika Virus
by Ian M. Bird, Victoria Cavener, Meera Surendran Nair, Ruth H. Nissly, Shubhada K. Chothe, Joshy Jacob and Suresh V. Kuchipudi
Microorganisms 2024, 12(9), 1840; https://doi.org/10.3390/microorganisms12091840 - 5 Sep 2024
Viewed by 872
Abstract
Zika virus (ZIKV), a mosquito-borne flavivirus, is a significant global health concern due to its association with neurodevelopmental disorders such as congenital Zika syndrome (CZS). This study aimed to compare the replication kinetics, viral persistence, cytopathogenic effects, and immune gene expression in human [...] Read more.
Zika virus (ZIKV), a mosquito-borne flavivirus, is a significant global health concern due to its association with neurodevelopmental disorders such as congenital Zika syndrome (CZS). This study aimed to compare the replication kinetics, viral persistence, cytopathogenic effects, and immune gene expression in human microglia cells (CHME-3) infected with an Asian lineage ZIKV (PRVABC59, referred to as ZIKV-PRV) and an African lineage ZIKV (IBH30656, referred to as ZIKV-IBH). We found that ZIKV-PRV replicated more efficiently and persisted longer while inducing lower levels of cell death and inflammatory gene activation compared with ZIKV-IBH. These findings suggest that the enhanced replication and persistence of ZIKV-PRV, along with its ability to evade innate immune responses, may underlie its increased neuropathogenic potential, especially in the context of CZS. In contrast, ZIKV-IBH, with its stronger immune gene activation and higher cytopathogenicity, may lead to more acute infections with faster viral clearance, thereby reducing the likelihood of chronic central nervous system (CNS) infection. This study provides crucial insights into the molecular and cellular mechanisms driving the differential pathogenicity of ZIKV lineages and highlights the need for further research to pinpoint the viral factors responsible for these distinct clinical outcomes. Full article
(This article belongs to the Special Issue Zika Virus Infection and Immune Response)
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20 pages, 1901 KiB  
Article
Transcriptomic Signatures of Zika Virus Infection in Patients and a Cell Culture Model
by Gillian Berglund, Claudia D. Lennon, Pheonah Badu, John Andrew Berglund and Cara T. Pager
Microorganisms 2024, 12(7), 1499; https://doi.org/10.3390/microorganisms12071499 - 22 Jul 2024
Cited by 2 | Viewed by 1124
Abstract
Zika virus (ZIKV), a re-emerging flavivirus, is associated with devasting developmental and neurological disease outcomes particularly in infants infected in utero. Towards understanding the molecular underpinnings of the unique ZIKV disease pathologies, numerous transcriptome-wide studies have been undertaken. Notably, these studies have overlooked [...] Read more.
Zika virus (ZIKV), a re-emerging flavivirus, is associated with devasting developmental and neurological disease outcomes particularly in infants infected in utero. Towards understanding the molecular underpinnings of the unique ZIKV disease pathologies, numerous transcriptome-wide studies have been undertaken. Notably, these studies have overlooked the assimilation of RNA-seq analysis from ZIKV-infected patients with cell culture model systems. In this study we find that ZIKV-infection of human lung adenocarcinoma A549 cells, mirrored both the transcriptional and alternative splicing profiles from previously published RNA-seq data of peripheral blood mononuclear cells collected from pediatric patients during early acute, late acute, and convalescent phases of ZIKV infection. Our analyses show that ZIKV infection in cultured cells correlates with transcriptional changes in patients, while the overlap in alternative splicing profiles was not as extensive. Overall, our data indicate that cell culture model systems support dissection of select molecular changes detected in patients and establishes the groundwork for future studies elucidating the biological implications of alternative splicing during ZIKV infection. Full article
(This article belongs to the Special Issue Zika Virus Infection and Immune Response)
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15 pages, 1653 KiB  
Article
Immunological and Safety Considerations When Selecting the Dose Formulation of a Purified Inactivated Zika Virus Vaccine (PIZV)
by Camilo J. Acosta, Francesco Nordio, Eloi Kpamegan, Kelley J. Moss, Pradeep Kumar and Kazuhiro Hirata
Microorganisms 2024, 12(7), 1492; https://doi.org/10.3390/microorganisms12071492 - 21 Jul 2024
Viewed by 1072
Abstract
We previously reported the first-in-human assessment of three doses (2, 5, and 10 µg) of purified inactivated Zika virus vaccine (PIZV or TAK-426) in the Phase 1 ZIK-101 study (NCT03343626). Here, we report dose selection based on extended safety and immunogenicity data (6 [...] Read more.
We previously reported the first-in-human assessment of three doses (2, 5, and 10 µg) of purified inactivated Zika virus vaccine (PIZV or TAK-426) in the Phase 1 ZIK-101 study (NCT03343626). Here, we report dose selection based on extended safety and immunogenicity data (6 months post-vaccination) and discuss considerations (e.g., immunological, historic, flavivirus immunological cross-reactions) for selecting a Zika virus (ZIKV) vaccine dose formulation. TAK-426 dose selection was conducted at the first interim analysis, and was based on cumulative safety data from both flavivirus-naïve (up to ≥28 days post-dose PD2) and flavivirus-primed participants (up to ≥28 days PD1), and on immunogenicity data from flavivirus-naïve participants only (at 28 days PD1 and 28 days PD2). The safety profile from TAK-426 recipients was compared to placebo recipients. Immunogenicity was assessed by geometric mean titer ratios of neutralizing anti-ZIKV antibodies and differences in seroconversion rates. There was no significant difference in safety between the three TAK-426 doses. The 10 μg dose provided the earliest and strongest immune response (with close to 100% seroconversion and higher antibody titers PD1 in flavivirus-naïve participants), and was well tolerated with acceptable safety profiles in both flavivirus-naïve and flavivirus-primed participants; this dose was selected for further development. Full article
(This article belongs to the Special Issue Zika Virus Infection and Immune Response)
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14 pages, 957 KiB  
Article
Predicting Efficacy of a Purified Inactivated Zika Virus Vaccine in Flavivirus-Naïve Humans Using an Immunological Correlate of Protection in Non-Human Primates
by Camilo J. Acosta, Francesco Nordio, David A. Boltz, Whitney R. Baldwin, Greg Hather and Eloi Kpamegan
Microorganisms 2024, 12(6), 1177; https://doi.org/10.3390/microorganisms12061177 - 11 Jun 2024
Cited by 1 | Viewed by 1121
Abstract
A traditional phase 3 clinical efficacy study for a Zika vaccine may be unfeasible because of the current low transmission of Zika virus (ZIKV). An alternative clinical development approach to evaluate Zika vaccine efficacy (VE) is therefore required, delineated in the US FDA’s [...] Read more.
A traditional phase 3 clinical efficacy study for a Zika vaccine may be unfeasible because of the current low transmission of Zika virus (ZIKV). An alternative clinical development approach to evaluate Zika vaccine efficacy (VE) is therefore required, delineated in the US FDA’s Accelerated Approval Program for licensure, which utilizes an anti-Zika neutralizing antibody (Zika NAb) titer correlated with non-human primate (NHP) protection as a surrogate endpoint. In this accelerated approval approach, the estimation of VE would be inferred from the percentage of phase 3 trial participants achieving the established surrogate endpoint. We provide a statistical framework to predict the probability of protection for human participants vaccinated with a purified inactivated ZIKV vaccine (TAK-426), in the absence of VE measurements, using NHP data under a single-correlate model. Based on a logistic regression (LR) with bias-reduction model, a probability of 90% protection in humans is expected with a ZIKV NAb geometric mean titer (GMT) ≥ 3.38 log10 half-maximal effective concentration (EC50). The predicted probability of protection of TAK-426 against ZIKV infection was determined using the two-parameter LR model that fit the calculated VE in rhesus macaques and the flavivirus-naïve phase 1 trial participants’ ZIKV NAb GMTs log10 EC50, measured by a ZIKV reporter virus particle assay, at 1 month post dose 2. The TAK-426 10 µg dose predicted a probability of protection from infection of 98% among flavivirus-naïve phase 1 trial participants. Full article
(This article belongs to the Special Issue Zika Virus Infection and Immune Response)
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