Quantification of dengue virus specific T cell responses and correlation with viral load and clinical disease severity in acute dengue infection

Wijeratne, Dulharie T.; Fernando, Samitha; Gomes, Laksiri; Jeewandara, Chandima; Ginneliya, Anushka; Samarasekara, Supun; Wijewickrama, Ananda; Hardman, Clare S.; Ogg, Graham S.; Malavige, Gathsaurie Neelika

doi:10.1371/journal.pntd.0006540

Cited by 34 publications

(41 citation statements)

References 45 publications

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“…Presence of sustained levels of IFN-γ prior and early after DENV challenge in vaccinees has been associated with protection against viremia and/or severe disease 64,65 . We observed a similar phenotype of the polyfunctional response of CD8 + T cells prior DENV infection in animals with longer convalescence to ZIKV.…”

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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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: 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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“…11 Moreover, we also found that the magnitude of the DENV-specific T-cell response inversely correlated with the degree of viraemia, further suggesting that T cells have a protective role in acute dengue. 11 Apart from the breadth and magnitude of a T-cell response, their functionality has also been shown to be crucial in protection against many infections. [12][13][14] Polyfunctional T cells that produce multiple types of cytokines have been shown to be protective and correlate with resolution of viraemia, especially in chronic viral infections.…”

Section: Introductionmentioning

confidence: 52%

“…Although we previously reported that IFNγ-producing T cells as determined by ex vivo ELISpot inversely correlated with the viraemia, we believe that we did not see a similar observation, as we only investigated CD8+ T cells in this study compared with the overall DENV-Tcell responses in our previous study. 11 In healthy individuals who were naturally exposed to the DENV, the majority of DENV-specific T cells produced two cytokines, irrespective whether they were simulated with conserved-or serotype-specific peptides. 7 However, we found that in acute infection only 18.1% to 23.3% of DENV-specific T cells produced two cytokines/ effectors, possibly due to the downregulation of T-cell receptor signaling pathways involved in cytokine during acute dengue.…”

Section: Discussionmentioning

confidence: 99%

Association of dengue virus‐specific polyfunctional T‐cell responses with clinical disease severity in acute dengue infection

Wijeratne

Fernando

Gomes

et al. 2019

Immunity Inflam & Disease

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Introduction Although the role of dengue virus (DENV)‐specific T cells in the pathogenesis of acute dengue infection is emerging, the functionality of virus‐specific T cells associated with milder clinical disease has not been well studied. We sought to investigate how the functionality of DENV–NS3 and DENV–NS5 protein‐specific T cells differ in patients with dengue fever (DF) and dengue hemorrhagic fever (DHF). Methods Using intracellular cytokine assays, we assessed the production of interferon γ (IFNγ), tumor necrosis factor‐α (TNF‐α), macrophage inflammatory protein‐1β (MIP‐1β), and CD107a expression in adult patients with acute DF (n = 21) and DHF (n = 22). Results Quadruple cytokine‐producing, polyfunctional DENV–NS3‐ and DENV–NS5‐specific T cells were more frequent in those with DF when compared to those with DHF. While DENV–NS3‐ and DENV–NS5‐specific T cells in patients with DF expressed IFNγ > TNF‐α > MIP‐β > CD107a, T cells of those with DHF predominantly expressed CD107a > MIP‐1β > IFNγ > TNF‐α. Overall production of IFNγ or TNF‐α by DENV–NS3‐ and DENV–NS5‐specific T cells was significantly higher in patients with DF. The majority of NS3‐specific T cells in patients with DF (78.6%) and DHF (68.9%) were single‐cytokine producers; 76.6% of DENV–NS5‐specific T cells in those with DF and 77.1% of those with DHF, produced only a single cytokine. However, no significant association was found with polyfunctional T‐cell responses and the degree of viraemia. Conclusions Our results suggest that the functional phenotype of DENV‐specific T cells are likely to associate with clinical disease severity.

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“…For example, in the case of flaviviruses, it has recently become evident that distinct T cell populations, virus serotypes, sequence, and number of infections, and HLA background all shape the immunodominance pattern (29). Additionally, patterns of T cell cytokine response among patients with a secondary DENV infection were associated with severe (51,52) or mild dengue (53,54). Although heterotypic antigens were addressed only in one of these studies (52), such observations may indicate involvement of cross-reactive T cells in the clinical manifestation of DENV infections.…”

Section: Protection Vs Immunopathologymentioning

confidence: 99%

Virus-Induced T Cell-Mediated Heterologous Immunity and Vaccine Development

et al. 2020

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Quantification of dengue virus specific T cell responses and correlation with viral load and clinical disease severity in acute dengue infection

Cited by 34 publications

References 45 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

Association of dengue virus‐specific polyfunctional T‐cell responses with clinical disease severity in acute dengue infection

Virus-Induced T Cell-Mediated Heterologous Immunity and Vaccine Development

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