Cross-Protection Against Four Serotypes of Dengue Virus in Mice Conferred by a Zika DNA Vaccine

Wang, Ran; Gao, Na; Li, Yun; Fan, Dongying; Zhen, Zi-Da; Feng, Kaihao; Chen, Hui; An, Jing

doi:10.3389/fcimb.2019.00147

Cited by 17 publications

(13 citation statements)

References 25 publications

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“…Therefore, it is still unclear whether systemic thrombo-inflammatory responses might converge with endothelial injury caused by DENV. Nevertheless, intracerebral inoculation of mice is a plausible in vivo model that allows virus replication and measurable clinical parameters [ 29 , 30 ], and have been standardly used in antiviral and vaccine preclinical trials [ 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

Contact System Activation in Plasma from Dengue Patients Might Harness Endothelial Virus Replication through the Signaling of Bradykinin Receptors

et al. 2021

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Since exacerbated inflammation and microvascular leakage are hallmarks of dengue virus (DENV) infection, here we interrogated whether systemic activation of the contact/kallikrein-kinin system (KKS) might hamper endothelial function. In vitro assays showed that dextran sulfate, a potent contact activator, failed to generate appreciable levels of activated plasma kallikrein (PKa) in the large majority of samples from a dengue cohort (n = 70), irrespective of severity of clinical symptoms. Impaired formation of PKa in dengue-plasmas correlated with the presence of cleaved Factor XII and high molecular weight kininogen (HK), suggesting that the prothrombogenic contact system is frequently triggered during the course of infection. Using two pathogenic arboviruses, DENV or Zika virus (ZIKV), we then asked whether exogenous BK could influence the outcome of infection of human brain microvascular endothelial cells (HBMECs). Unlike the unresponsive phenotype of Zika-infected HBMECs, we found that BK, acting via B2R, vigorously stimulated DENV-2 replication by reverting nitric oxide-driven apoptosis of endothelial cells. Using the mouse model of cerebral dengue infection, we next demonstrated that B2R targeting by icatibant decreased viral load in brain tissues. In summary, our study suggests that contact/KKS activation followed by BK-induced enhancement of DENV replication in the endothelium may underlie microvascular pathology in dengue.

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Section: Introductionmentioning

confidence: 99%

Contact System Activation in Plasma from Dengue Patients Might Harness Endothelial Virus Replication through the Signaling of Bradykinin Receptors

et al. 2021

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“…Currently, several studies have indicated complex interactions between DENV and ZIKV immunity (Breitbach et al 2019 ; Fowler et al 2018 ; Pantoja et al 2017 ; Slon-Campos et al 2019 ; Wang et al 2019a ; Zimmerman et al 2018 ). Clinical data suggest that pre-existing DENV immunity is partially protective against symptomatic ZIKV infection and against congenital ZIKV syndrome (Gordon et al 2019 ; Pedroso et al 2019 ).…”

Section: Introductionmentioning

confidence: 99%

T cell immunity rather than antibody mediates cross-protection against Zika virus infection conferred by a live attenuated Japanese encephalitis SA14-14-2 vaccine

Wang

Zhen

Turtle

et al. 2020

Appl Microbiol Biotechnol

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Zika virus (ZIKV) and Japanese encephalitis virus (JEV) are closely related to mosquito-borne flaviviruses. Japanese encephalitis (JE) vaccine SA14-14-2 has been in the Chinese national Expanded Program on Immunization since 2007. The recent recognition of severe disease syndromes associated with ZIKV, and the identification of ZIKV from mosquitoes in China, prompts an urgent need to investigate the potential interaction between the two. In this study, we showed that SA14-14-2 is protective against ZIKV infection in mice. JE vaccine SA14-14-2 triggered both Th1 and Th2 cross-reactive immune responses to ZIKV; however, it was cellular immunity that predominantly mediated cross-protection against ZIKV infection. Passive transfer of immune sera did not result in significant cross-protection but did mediate antibody-dependent enhancement in vitro, though this did not have an adverse impact on survival. This study suggests that the SA14-14-2 vaccine can protect against ZIKV through a cross-reactive T cell response. This is vital information in terms of ZIKV prevention or precaution in those ZIKV-affected regions where JEV circulates or SA14-14-2 is in widespread use, and opens a promising avenue to develop a novel bivalent vaccine against both ZIKV and JEV. Key points • JEV SA14-14-2 vaccine conferred cross-protection against ZIKV challenge in mice. • T cell immunity rather than antibody mediated the cross-protection. • It provides important information in terms of ZIKV prevention or precaution.

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“…Currently, several studies have indicated complex interactions between DENV and ZIKV immunity (7-12). Clinical data suggest that pre-existing DENV immunity is partially protective against symptomatic ZIKV infection and against congenital ZIKV syndrome (13, 14).…”

Section: Introductionmentioning

confidence: 99%

Cross-Protection Against Zika Virus Infection Conferred by a Live Attenuated Japanese Encephalitis SA14-14-2 Vaccine

Wang

Zhen

Turtle

et al. 2020

Preprint

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24Zika virus (ZIKV) and Japanese encephalitis virus (JEV) are closely related 25 mosquito-borne flaviviruses. Japanese encephalitis (JE) vaccine SA14-14-2 has been in 26 the Chinese national Expanded Program on Immunization since 2007. The recent 27 recognition of severe disease syndromes associated with ZIKV, and the identification of 28 ZIKV from mosquitoes in China, prompts an urgent need to investigate the potential 29 interaction between the two. In this study, we showed that SA14-14-2 is protective against 30 ZIKV infection in mice. JE vaccine SA14-14-2 triggered both Th1 and Th2 cross-reactive 31 immune responses to ZIKV; however, it was cellular immunity that predominantly 32 mediated cross-protection against ZIKV infection. Passive transfer of immune sera did not 33 result in significant cross-protection, but did mediate antibody dependent enhancement in 34 vitro, though this did not have an adverse impact on survival. This study suggests that 35 SA14-14-2 vaccine can protect against ZIKV through a cross-reactive T cell response. 36This is vital information in terms of ZIKV prevention or precaution in those ZIKV-affected 37 regions where JEV circulates or SA14-14-2 is in widespread use, and opens a promising 38 avenue into developing a novel bivalent vaccine against both ZIKV and JEV. 40Importance 43 Japanese encephalitis is a controllable disease in many countries in Asia, especially in 44 China, where many people have Japanese encephalitis virus (JEV) immunity due to 45 extensive JEV vaccination campaigns or natural exposure. Live-attenuated SA14-14-2 46 strain is a safe and effective vaccine recommended by the World Health Organization and 47 has been vaccinated more than 600 million doses since 1989. As the prevalence of Zika 48 virus (ZIKV) and rising risk in above regions, the cross-reactive immune response 49 between these two antigenically closely related flaviviruses, JEV and ZIKV, should also be 50 fully recognized, which is presumed to be based on those ambiguous cross-reactive 51 immunity between dengue virus and ZIKV. In this study, we found that JEV SA14-14-2 52 vaccine conferred cross-protection against ZIKV challenge in mice, which is mainly due to 53 cellular immunity rather than neutralizing antibody response. However, specific protective 54 components or cooperation between components warrant to be explored in subsequent 55 experiments. In conclusion, this study can provide important evidence for those who live in 56 JEV-endemic areas and are at risk for ZIKV infection.57 4 Introduction 58 Recently, Zika virus (ZIKV) has caused devastating outbreaks of fetal congenital 59 malformations in South and Central America and now transmitted in more than 70 60 countries, including many previously unaffected regions. ZIKV infection during pregnancy 61 increases the risk of neurological disorders in newborns (1), such as microcephaly. In 62 adults, ZIKV causes Guillain-Barré syndrome and other neurologic disorders (2). So far, 63 no specific vaccine or antiviral for prevention and treatment of Z...

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Cross-Protection Against Four Serotypes of Dengue Virus in Mice Conferred by a Zika DNA Vaccine

Cited by 17 publications

References 25 publications

Contact System Activation in Plasma from Dengue Patients Might Harness Endothelial Virus Replication through the Signaling of Bradykinin Receptors

Contact System Activation in Plasma from Dengue Patients Might Harness Endothelial Virus Replication through the Signaling of Bradykinin Receptors

T cell immunity rather than antibody mediates cross-protection against Zika virus infection conferred by a live attenuated Japanese encephalitis SA14-14-2 vaccine

Cross-Protection Against Zika Virus Infection Conferred by a Live Attenuated Japanese Encephalitis SA14-14-2 Vaccine

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