Zika Virus–Induced Antibody Response Enhances Dengue Virus Serotype 2 Replication In Vitro

Kawiecki, Anna B.; Christofferson, Rebecca C.

doi:10.1093/infdis/jiw377

Cited by 108 publications

(87 citation statements)

References 13 publications

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“…This phenomenon could be relevant to ZIKV vaccination because DENV and ZIKV are related closely, and vaccinated subjects in or travelers to endemic areas could become exposed secondarily to DENV, which infects ~390 million people per year (Bhatt et al, 2013). Indeed, cross-reactive antibodies targeting the highly conserved fusion loop in DII of E (E-DII-FL) derived during natural ZIKV infection can augment infectivity of DENV in cell culture Kawiecki and Christofferson, 2016;Stettler et al, 2016) and in vivo in mice (Stettler et al, 2016). This laboratory-based data is not conclusive, as epidemiological studies, which may take years to perform, are required to establish the impact of ZIKV humoral immunity on DENV pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

Modified mRNA Vaccines Protect against Zika Virus Infection

Richner¹,

Himansu²,

Dowd³

et al. 2017

Cell

215

189

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SUMMARYThe emergence of ZIKV infection has prompted a global effort to develop safe and effective vaccines. We engineered a lipid nanoparticle (LNP) encapsulated modified mRNA vaccine encoding wild-type or variant ZIKV structural genes and tested immunogenicity and protection in mice. Two doses of modified mRNA LNPs encoding prM-E genes that produced virus-like particles resulted in high neutralizing antibody titers (~ 1/100,000) that protected against ZIKV infection and conferred sterilizing immunity. To offset a theoretical concern of ZIKV vaccines Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. eTOC A modified mRNA vaccine induces sterilizing immunity against Zika virus while avoiding the generation of cross-reactive antibodies that may enhance dengue infection. AUTHOR CONTRIBUTION HHS Public Access

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Section: Introductionmentioning

confidence: 99%

Modified mRNA Vaccines Protect against Zika Virus Infection

Richner¹,

Himansu²,

Dowd³

et al. 2017

Cell

215

189

View full text Add to dashboard Cite

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“…Though studies in nonhuman primates [5] and mice [8] have shown the potential for ZIKV-induced cross-reactive responses to enhance DENV infection, there are limited data to support these findings in humans. Our results show that serum from ZIKV-infected human subjects was capable of mediating the ADE of DENV infection in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…Our results show that serum from ZIKV-infected human subjects was capable of mediating the ADE of DENV infection in vitro. Large epidemiological studies are needed to determine if these findings directly translate to the potential for higher risk of severe dengue, but they add to the evidence from animal studies that ZIKV-induced antibodies could potentially enhance DENV infection; monoclonal antibodies [9] or polyclonal serum [8] has been shown to enhance DENV infection in vitro, whereas ZIKV-convalescent nonhuman primates experienced enhanced DENV viremia following infection with DENV [1–3]. …”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, induction of cross-reactive antibodies in the absence of cross-neutralization was associated with significant enhancement of DENV infection in vivo in rhesus macaques [5]. Likewise, polyclonal serum from wild-type mice injected with ZIKV and monoclonal antibodies isolated from a human subject previously infected with ZIKV was shown to enhance DENV infection of monocytes in vitro [8, 9]. …”

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confidence: 99%

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Human Serum With High Neutralizing Antibody Titers Against Both Zika and Dengue Virus Shows Delayed In Vitro Antibody-Dependent Enhancement of Dengue Virus Infection

Valiant

Lalani

Yun

et al. 2018

Open Forum Infectious Diseases

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Zika virus infection in a dengue virus–naïve subject was associated with the induction of high levels of cross-reactive binding antibodies. These responses were, however, largely non-neutralizing and displayed a capacity to enhance dengue infection in vitro at significantly low dilution (1:10). In contrast, a subject who had high levels of neutralizing antibodies against both dengue and Zika viruses enhanced infection at a dilution of 1:10 000. These results suggest that high levels of dengue cross-neutralizing antibodies could potentially prevent the enhancement of dengue infection in Zika virus–convalescent individuals.

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“…To examine the long term impact of dengue vaccine on Zika transmission, we should also consider the issue whether dengue vaccine offers only short-term protection (and hence ADE), which can be modelled by allowing recovery to the dengue-susceptible populations. Finally, in view of the recent study [49] on bidirectional ADE impact between dengue and Zika, and the substantial global efforts towards Zika vaccine development, our model should be modified by further stratification of the vector and human populations and additional cost-benefit analyses to inform “long-term high prioritisation and adequate resources” [50]. …”

Section: Limitationsmentioning

confidence: 99%

A conceptual model for optimizing vaccine coverage to reduce vector-borne infections in the presence of antibody-dependent enhancement

Tang

Xiao

et al. 2018

Theor Biol Med Model

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BackgroundMany vector-borne diseases co-circulate, as the viruses from the same family are also transmitted by the same vector species. For example, Zika and dengue viruses belong to the same Flavivirus family and are primarily transmitted by a common mosquito species Aedes aegypti. Zika outbreaks have also commonly occurred in dengue-endemic areas, and co-circulation and co-infection of both viruses have been reported. As recent immunological cross-reactivity studies have confirmed that convalescent plasma following dengue infection can enhance Zika infection, and as global efforts of developing dengue and Zika vaccines are intensified, it is important to examine whether and how vaccination against one disease in a large population may affect infection dynamics of another disease due to antibody-dependent enhancement.MethodsThrough a conceptual co-infection dynamics model parametrized by reported dengue and Zika epidemic and immunological cross-reactivity characteristics, we evaluate impact of a hypothetical dengue vaccination program on Zika infection dynamics in a single season when only one particular dengue serotype is involved.ResultsWe show that an appropriately designed and optimized dengue vaccination program can not only help control the dengue spread but also, counter-intuitively, reduce Zika infections. We identify optimal dengue vaccination coverages for controlling dengue and simultaneously reducing Zika infections, as well as the critical coverages exceeding which dengue vaccination will increase Zika infections.ConclusionThis study based on a conceptual model shows the promise of an integrative vector-borne disease control strategy involving optimal vaccination programs, in regions where different viruses or different serotypes of the same virus co-circulate, and convalescent plasma following infection from one virus (serotype) can enhance infection against another virus (serotype). The conceptual model provides a first step towards well-designed regional and global vector-borne disease immunization programs.

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Zika Virus–Induced Antibody Response Enhances Dengue Virus Serotype 2 Replication In Vitro

Cited by 108 publications

References 13 publications

Modified mRNA Vaccines Protect against Zika Virus Infection

Modified mRNA Vaccines Protect against Zika Virus Infection

Human Serum With High Neutralizing Antibody Titers Against Both Zika and Dengue Virus Shows Delayed In Vitro Antibody-Dependent Enhancement of Dengue Virus Infection

A conceptual model for optimizing vaccine coverage to reduce vector-borne infections in the presence of antibody-dependent enhancement

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