Dengue virus-reactive CD8+ T cells mediate cross-protection against subsequent Zika virus challenge

Wen, Jianping; Ngono, Annie Elong; Regla-Nava, José Ángel; Kim, Kenneth S.; Gorman, Matthew J.; Diamond, Michael S.; Shresta, Sujan

doi:10.1038/s41467-017-01669-z

Cited by 133 publications

(147 citation statements)

References 73 publications

(99 reference statements)

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“…However, recent results from our group and others have shown that previous flavivirus exposure-including DENV-may have no detrimental impact on ZIKV infection in vivo in non-human primates (NHP) 17,18 and humans 19 . Moreover, these studies and others suggest that previous DENV immunity may play a protective role during ZIKV infection involving humoral and cellular responses [20][21][22][23][24] . On the other hand, little is known about the opposite scenario, the role of a previous ZIKV exposure on a subsequent DENV infection, which is relevant to anticipate the dynamics of forthcoming DENV epidemics.…”

Section: Introductionmentioning

confidence: 70%

“…Early studies of T cells associate their contribution towards immunopathogenesis in DENV secondary infections explained by the original antigenic sin 59 , but increasing evidence suggest their protective role during primary and secondary DENV infections 60 . Recently, with the introduction of ZIKV into The Americas, T cells from DENV immunity are being implicated in mediating cross-protection against ZIKV [22][23][24] . However, the role and kinetics of T cells from ZIKV immunity in a subsequent DENV infection remains unknown.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Time elapsed between Zika and dengue virus infections affects antibody and T cell responses

Pérez-Guzmán

Pantoja

Serrano-Collazo

et al. 2019

Preprint

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34The role of Zika virus (ZIKV) immunity on subsequent dengue virus (DENV) infections is 35 relevant to anticipate the dynamics of forthcoming DENV epidemics in areas with previous ZIKV 36 exposure. We study the effect of ZIKV infection with various strains on subsequent DENV 37 immune response after 10 and 2 months of ZIKV infection in rhesus macaques. Our results 38show that a subsequent DENV infection in animals with early-and middle-convalescent periods 39 to ZIKV do not promote an increase in DENV viremia nor pro-inflammatory status. Previous 40 ZIKV exposure increases the magnitude of the antibody and T cell responses against DENV, 41 and different time intervals between infections alter the magnitude and durability of such 42 responses-more after longer ZIKV pre-exposure. Collectively, we find no evidence of a 43 detrimental effect of ZIKV immunity in a subsequent DENV infection. This supports the 44 implementation of ZIKV vaccines that could also boost immunity against future DENV 45 epidemics. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61Zika virus (ZIKV) is a re-emerging mosquito-borne Flavivirus that has captivated the 62 attention of the scientific community by its explosive spread in The Americas 1 , and severe 63 neurological sequelae following infection 2-4 . ZIKV established itself in tropical and sub-tropical 64 regions that are endemic to other closely-related flaviviruses such as dengue virus (DENV). 65Both viruses belong to the Flaviviridae family and are transmitted by Aedes spp. mosquitoes. 66DENV is a global public health threat, having two-thirds of world's population at risk of infection, 67 causing ~390 million infections annually 5,6 . DENV exists as four genetically similar but 68 antigenically different serotypes (DENV1-4) 7 . Exposure to one DENV serotype confers long-69 lived immunity against a homotypic secondary infection. However, secondary infection with a 70 heterologous serotype of DENV is the major risk factor to induce severe DENV disease [8][9][10] . 71Due to the antigenic similarities between DENV and ZIKV, concerns have been raised 72 regarding the impact of DENV-ZIKV cross-reactive immunity on the development of severe 73 clinical manifestations 11,12 . It has been demonstrated that DENV-immune sera from humans can 74 enhance ZIKV infection in vitro 13,14 , and in vivo in immune-deficient mouse models 15 . However, 75 recent results from our group and others have shown that previous flavivirus exposure-76including DENV-may have no detrimental impact on ZIKV infection in vivo in non-human 77 primates (NHP) 16,17 and humans 18 . Moreover, these studies and others suggest that previous 78 DENV immunity may play a protective role during ZIKV infection involving humoral and cellular 79 responses 19-23 . On the other hand, little is known about the opposite scenario, the role of a 80 previous ZIKV exposure on subsequent DENV infection, which is relevant to anticipate the 81 dynamics of forthcoming DENV epidemics. 82The recent ZIKV epidemic in the Americas resulted in t...

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Section: Introductionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Time elapsed between Zika and dengue virus infections affects antibody and T cell responses

Pérez-Guzmán

Pantoja

Serrano-Collazo

et al. 2019

Preprint

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“…The protective role of the cellular immune response controlling the viral burden of ZIKV in mice has been reported (76, 77). More recently mouse models have shown that prior DENV immunity can protect against ZIKV infection during pregnancy, and CD8+ T cells are sufficient for this cross-protection (78).…”

Section: Discussionmentioning

confidence: 99%

Significant control of Zika infection in macaques depends on the elapsing time after dengue exposure

Serrano-Collazo

Pantoja

et al. 2019

Preprint

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29Prior exposure to a single serotype of dengue virus (DENV) predisposes individuals to severe 30 disease upon secondary heterologous DENV infection. Here we show that the length of time 31 between DENV/Zika (ZIKV) infections has a qualitative impact on controlling ZIKV replication. 32We identified limited but significant differences in the magnitude of the early humoral immune 33 response associated with a period of twelve months but not three months of DENV 34 convalescence. However, their role limiting ZIKV replication is not conclusive. There was no 35 evidence of in vivo antibody-dependent amplification of ZIKV by DENV immunity in any group. 36We are also showing that the significant differences among groups may be linked to a pre-37 existing polyfunctional CD4+ T cells response (increased IFN-g and Cd107a before ZIKV 38 infection) and to an early and continuous expansion of the CD4+ effector memory cells early on 39 after ZIKV infection. Those significant differences were associated with a period of 12 months 40 after DENV infection that were not observed in a span of 3-months. These results suggest that 41 there is a window of optimal cross-protection between ZIKV and DENV with significant 42 consequences. These results have pivotal implications while interpreting ZIKV pathogenesis in 43 flavivirus-experimented populations, diagnostic results interpretation and vaccine designs 44 among others. 45 46 Author Summary 47impact on controlling the ZIKV infection. In this study, as in our prior work we did not observe 100 evidence of ZIKV disease enhancement associated with prior DENV exposure. We also 101 confirmed that the significant differences among groups are mediated by the pre-existence of a 102 robust effector memory T cell (TEM) and cytotoxic activity mainly mediated by CD4 + T cells 103 more than qualitative differences in the humoral immune response. However, by conducting a 104 detailed study of the ZIKV-neutralizing titers vs. ZIKV RNAemia at early time points after 105 infection, we were able to determine a possible contribution of the neutralizing antibodies 106 limiting the ZIKV replication at 7 days after infection in the animals with 12 months but not 3 107 months of DENV immunity or in the control group. Overall, we demonstrated that exposure to 108 ZIKV 12 months after DENV infection afford a high level of T cell-mediated cross protection than 109 it was observed at the 3-month span. Based on our previous study we believe this protection 110 wanes as macaques exposed to ZIKV 2.8 years after DENV were not afforded this protection. 111These results suggest that there is a window of optimal T cell cross-protection between ZIKV 112 and DENV. 113 114 Results 115

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“…However, our study demonstrated that the highest average force of infection values are found in provinces with mean temperatures between 20 and 26°C (Table 1), and laboratory studies confirm that Zika virus can be detected in the salivary glands of Aedes aegypti and transmitted at 25°C [63]. There are several possible hypotheses that could explain this discrepancy, including that: 1) provinces with mean temperatures around 29°C already implement vector control; 2) people may have acquired cross-immunity from exposure to other arboviruses [25,64,65]; and/or 3) given suitable temperature for transmission, other factors that can covary with temperature such as land use, urbanization, and socioeconomics may be more important drivers of large epidemics [20]. These hypotheses raise important questions about how to reconcile and ground truth theoretical and empirical studies with field data.…”

Section: Discussionmentioning

confidence: 99%

Climate drives spatial variation in Zika epidemics in Latin America

Harris

Caldwell

Mordecai

2018

Preprint

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24Between 2015 and 2017, Zika virus spread rapidly through populations in the Americas with no 25 prior exposure to the disease. Although climate is a known determinant of many Aedes- 26 transmitted diseases, it is currently unclear whether climate was a major driver the of Zika 27 epidemic and how climate might have differentially impacted outbreak intensity across locations 28 within Latin America. Here, we estimated force of infection for Zika over time and across 29 provinces in Latin America using a time-varying Susceptible Infectious Recovered model. 30 Climate factors explained less than 5% of the variation in weekly transmission intensity in a 31 spatiotemporal model of force of infection by province over time, suggesting that week to week 32 transmission within provinces may be too stochastic to predict. By contrast, climate and 33 population factors were highly predictive of spatial variation in the presence and intensity of 34 Zika transmission among provinces, with pseudo R 2 values between 0.33 and 0.60. Temperature, 35 temperature range, rainfall, and population size were the most important predictors of where 36 Zika transmission occurred, while rainfall, relative humidity, and a nonlinear effect of 37 temperature were the best predictors of Zika intensity and burden. Surprisingly, force of 38 infection was greatest in locations with temperatures near 24°C, much lower than previous 39 estimates from mechanistic models, potentially suggesting that existing vector control programs 40 and/or prior exposure to other mosquito-borne diseases may have limited transmission in 41 locations most suitable for Aedes aegypti, the main vector of Zika, dengue, and chikungunya 42 viruses in Latin America. 43 44 45 46 48health concern, yet trends in mosquito-borne disease transmission are hard to predict because 49 they are influenced by the underlying immunity in the population, which is usually unknown [1-50 3]. The emergence and spread of Zika virus through Latin America in a population with no prior 51 exposure or immunity to the disease provides an opportunity to characterize relationships among 52 the environment, populations, and disease transmission without the confounding effects of pre-53 existing immunity (although cross-reactivity between dengue antibodies and Zika virus may 54 provide some protection) [4]. Between 2015 and 2017, Zika rapidly spread to 51 countries and 55 territories in the Americas, with over 800,000 cases reported [5]. Here, we quantified the force of 56 infection for Zika and studied factors that contributed to variation in transmission across time 57 and space as Zika emerged. 58 Force of infection, or the per capita rate at which susceptible individuals contract an 59 infection, can be used to compare disease transmission over the course of an outbreak and across 60 geographic regions [2,6]. Force of infection estimates can account for variation in the number of 61 immune individuals and entomological factors that influence the time it takes for mosquito-borne 62dise...

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Dengue virus-reactive CD8+ T cells mediate cross-protection against subsequent Zika virus challenge

Cited by 133 publications

References 73 publications

Time elapsed between Zika and dengue virus infections affects antibody and T cell responses

Time elapsed between Zika and dengue virus infections affects antibody and T cell responses

Significant control of Zika infection in macaques depends on the elapsing time after dengue exposure

Climate drives spatial variation in Zika epidemics in Latin America

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