Dengue and Zika Virus Infections Are Enhanced by Live Attenuated Dengue Vaccine but Not by Recombinant DSV4 Vaccine Candidate in Mouse Models

Background: Globally, the recent outbreak of Zika virus (ZIKV) in Brazil, Asia Pacific, and other countries highlighted the unmet medical needs. Currently, there are neither effective vaccines nor therapeutics available to prevent or treat ZIKV infection. Objective: In this study, we aimed to design an epitope-based vaccine for ZIKV using an in silico approach to predict and analyze B- and T-cell epitopes. Methods: The prediction of the most antigenic epitopes has targeted the capsid and the envelope proteins as well as nonstructural proteins NS5 and NS3 using immune-informatics tools PROTPARAM, CFSSP, PSIPRED, and Vaxijen v2.0. B and T-cell epitopes were predicted using ABCpred, IEDB, TepiTool, and their toxicity were evaluated using ToxinPred. The 3-dimensional epitope structures were generated by PEP-FOLD. Energy minimization was performed using Swiss-Pdb Viewer, and molecular docking was conducted using PatchDock and FireDock server. Results: As a result, we predicted 307 epitopes of MHCI (major histocompatibility complex class I) and 102 epitopes of MHCII (major histocompatibility complex class II). Based on immunogenicity and antigenicity scores, we identified the four most antigenic MHC I epitopes: MVLAILAFLR (HLA-A*68 :01), ETLHGTVTV (HLA-A*68 :02), DENHPYRTW (HLA-B*44 :02),QEGVFHTMW (HLA-B*44 :03) and TASGRVIEEW (HLA-B*58:01), and MHC II epitopes: IIKKFKKDLAAMLRI (HLA-DRB3*02 :02), ENSKMMLELDPPFGD (HLA-DRB3*01:01), HAETWFFDENHPYRT (HLA-DRB3*01:01), TDGVYRVMTRRLLGS (HLA-DRB1*11 :01), and DGCWYGMEIRPRKEP (HLA-DRB5*01:01). Conclusion : This study provides novel potential B cell and T cell epitopes to fight Zika virus infections and may prompt further development of vaccines against ZIKV and other emerging infectious diseases. However, further investigations for protective immune response by in vitro and in vivo studies to ratify the immunogenicity, safety of the predicted structure, and ultimately the vaccine properties to prevent ZIKV infections are warranted.

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Immunogenicity and Safety of Yellow Fever Vaccine (Stamaril) When Administered Concomitantly With a Tetravalent Dengue Vaccine Candidate in Healthy Toddlers at 12–13 Months of Age in Colombia and Peru

The Pediatric Infectious Disease Journal ◽

10.1097/inf.0000000000001250 ◽

2016 ◽

Vol 35 (10) ◽

pp. 1140-1147 ◽

Cited By ~ 9

Author(s):

Pio López ◽

Claudio F. Lanata ◽

Betzana Zambrano ◽

Margarita Cortés ◽

Teresa Andrade ◽

...

Keyword(s):

Yellow Fever ◽

Vaccine Candidate ◽

Yellow Fever Vaccine ◽

Dengue Vaccine

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Serological Differences after Acute Zika Virus Infections between Children and Adults: Implication for Use of a Serological Test

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.21-0134 ◽

2021 ◽

Author(s):

Jurai Wongsawat ◽

Patama Suttha ◽

Sumalee Chanama ◽

Somkid Srisopa ◽

Nichapa Yonchoho ◽

...

Keyword(s):

Zika Virus ◽

Nonstructural Protein ◽

Serological Test ◽

Cross Reactivity ◽

Virus Infections ◽

Positive Real ◽

Nonstructural Protein 1 ◽

Age Related ◽

Polymerase Chain ◽

Post Onset

Information is limited regarding differential serological responses after acute Zika virus (ZIKV) infections and prevalence of cross-reactivity with anti-dengue virus (DENV) assays comparing children and adults. Early convalescent sera from a cohort of suspected mild DENV cases between December 2016 and September 2018 at Bamrasnaradura Infectious Diseases Institute in Thailand were tested for nonstructural protein 1 (NS1)–based anti-ZIKV IgM and IgG ELISAs (Euroimmun), and in-house anti-DENV IgM- and IgG-capture ELISAs. ZIKV cases were identified by positive real-time reverse transcriptase-polymerase chain reaction on urine. Sera from 26 (10 children and 16 adults) ZIKV and 237 (153 children and 74 adults) non-ZIKA cases collected at the median duration of 18 days (interquartile range [IQR] 18,19) post-onset of symptoms were tested. Comparing pediatric ZIKV to adult ZIKV cases, the mean anti-ZIKV IgM ratio was higher (2.12 versus 1.27 units, respectively; P = 0.07), whereas mean anti-ZIKV IgG ratio was lower (3.13 versus 4.24 units, respectively; P = 0.03). Sensitivity of anti-ZIKV IgM and specificity of anti-ZIKV IgG in pediatric ZIKV were higher than in adult ZIKV cases (80.0% versus 43.7% and 79.1% versus 43.2%, respectively). No cross-reactivity with anti-DENV IgM- and IgG-capture ELISA were reported in pediatric ZIKV cases in our study, whereas 25% and 12.5% were found in adult ZIKV cases, respectively. Age-related ZIKV serological differences have been observed. Positive NS1-based anti-ZIKV IgM and IgG ELISA at the early convalescent phase could be useful for ZIKV diagnosis in children, even in a dengue endemic setting.

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Treatment of Human Glioblastoma with a Live Attenuated Zika Virus Vaccine Candidate

mBio ◽

10.1128/mbio.01683-18 ◽

2018 ◽

Vol 9 (5) ◽

Cited By ~ 31

Author(s):

Qi Chen ◽

Jin Wu ◽

Qing Ye ◽

Feng Ma ◽

Qian Zhu ◽

...

Keyword(s):

Stem Cells ◽

Brain Tumor ◽

Zika Virus ◽

Vaccine Candidate ◽

Cell Subpopulation ◽

Glioma Stem Cells ◽

Intracerebral Injection ◽

Potential Candidate ◽

Orthotopic Model ◽

Human Gbm

ABSTRACT Glioblastoma (GBM) is the deadliest type of brain tumor, and glioma stem cells (GSCs) contribute to tumor recurrence and therapeutic resistance. Thus, an oncolytic virus targeting GSCs may be useful for improving GBM treatment. Because Zika virus (ZIKV) has an oncolytic tropism for infecting GSCs, we investigated the safety and efficacy of a live attenuated ZIKV vaccine candidate (ZIKV-LAV) for the treatment of human GBM in a GSC-derived orthotopic model. Intracerebral injection of ZIKV-LAV into mice caused no neurological symptoms or behavioral abnormalities. The neurovirulence of ZIKV-LAV was more attenuated than that of the licensed Japanese encephalitis virus LAV 14-14-2, underlining the superior safety of ZIKV-LAV for potential GBM treatment. Importantly, ZIKV-LAV significantly reduced intracerebral tumor growth and prolonged animal survival by selectively killing GSCs within the tumor. Mechanistically, ZIKV infection elicited antiviral immunity, inflammation, and GSC apoptosis. Together, these results further support the clinical development of ZIKV-LAV for GBM therapy. IMPORTANCE Glioblastoma (GBM), the deadliest type of brain tumor, is currently incurable because of its high recurrence rate after traditional treatments, including surgery to remove the main part of the tumor and radiation and chemotherapy to target residual tumor cells. These treatments fail mainly due to the presence of a cell subpopulation called glioma stem cells (GSCs), which are resistant to radiation and chemotherapy and capable of self-renewal and tumorigenicity. Because Zika virus (ZIKV) has an oncolytic tropism for infecting GSCs, we tested a live attenuated ZIKV vaccine candidate (ZIKV-LAV) for the treatment of human GBM in a human GSC-derived orthotopic model. Our results showed that ZIKV-LAV retained good efficacy against glioblastoma by selectively killing GSCs within the tumor. In addition, ZIKV-LAV exhibited an excellent safety profile upon intracerebral injection into the treated animals. The good balance between the safety of ZIKV-LAV and its efficacy against human GSCs suggests that it is a potential candidate for combination with the current treatment regimen for GBM therapy.

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Two Complex, Adenovirus-Based Vaccines That Together Induce Immune Responses to All Four Dengue Virus Serotypes

Clinical and Vaccine Immunology ◽

10.1128/cvi.00330-06 ◽

2006 ◽

Vol 14 (2) ◽

pp. 182-189 ◽

Cited By ~ 32

Author(s):

David H. Holman ◽

Danher Wang ◽

Kanakatte Raviprakash ◽

Nicholas U. Raja ◽

Min Luo ◽

...

Keyword(s):

Immune Responses ◽

Dengue Virus ◽

Vaccine Development ◽

De Novo ◽

Natural Infection ◽

Hemorrhagic Fever ◽

Virus Infections ◽

Dengue Vaccine ◽

Membrane Antigens ◽

Dengue Virus Serotypes

ABSTRACT Dengue virus infections can cause hemorrhagic fever, shock, encephalitis, and even death. Worldwide, approximately 2.5 billion people live in dengue-infested regions with about 100 million new cases each year, although many of these infections are believed to be silent. There are four antigenically distinct serotypes of dengue virus; thus, immunity from one serotype will not cross-protect from infection with the other three. The difficulties that hamper vaccine development include requirements of the natural conformation of the envelope glycoprotein to induce neutralizing immune responses and the necessity of presenting antigens of all four serotypes. Currently, the only way to meet these requirements is to use a mixture of four serotypes of live attenuated dengue viruses, but safety remains a major problem. In this study, we have developed the basis for a tetravalent dengue vaccine using a novel complex adenovirus platform that is capable of expressing multiple antigens de novo. This dengue vaccine is constructed as a pair of vectors that each expresses the premembrane and envelope genes of two different dengue virus serotypes. Upon vaccination, the vaccine expressed high levels of the dengue virus antigens in cells to mimic a natural infection and induced both humoral and cellular immune responses against multiple serotypes of dengue virus in an animal model. Further analyses show the humoral responses were indeed neutralizing against all four serotypes. Our studies demonstrate the concept of mimicking infections to induce immune responses by synthesizing dengue virus membrane antigens de novo and the feasibility of developing an effective tetravalent dengue vaccine by vector-mediated expression of glycoproteins of the four serotypes.

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