<i>Flavivirus</i>
            serocomplex cross-reactive immunity is protective by activating heterologous memory CD4 T cells

Saron, Wilfried A. A.; Rathore, Abhay P. S.; Lim, Ting; Ooi, Eng Eong; Low, Jenny Guek‐Hong; Abraham, Soman N.; John, Ashley L. St.

doi:10.1126/sciadv.aar4297

Cited by 73 publications

(96 citation statements)

References 67 publications

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“…Peptides derived from the aforementioned sequences were used to prime antigen presenting cells, which were subsequently used to stimulate splenocytes of DENV immunized mice. Some of these peptides induced enrichment of T memory cells as well as IFNγ production and proliferation, confirming cross-reactivity (33).…”

Section: Flavivirusessupporting

confidence: 61%

“…This protection was conferred by CD8 + T cells, limiting trans-placental transmission of ZIKV (32). Although cross-reactivity between DENV and ZIKV is the most prominent example, other flaviviruses, such as yellow fever virus (YFV) and Japanese encephalitis virus, also prime T cell responses toward a subsequent heterologous DENV infection in mice (33). In this context, the investigators identified homologous sequences between the flavivirus polyproteins.…”

Section: Flavivirusesmentioning

confidence: 99%

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

et al. 2020

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Section: Flavivirusessupporting

confidence: 61%

Section: Flavivirusesmentioning

confidence: 99%

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

et al. 2020

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“…Enzyme-linked immunosorbent assay (ELISA)], supporting its close relationship to DENV but indicating that it falls into an independent serocomplex (11,12). First described using human sera, these flavivirus cross-reactive immune responses appear to be consistent for multiple mammalian species, including rodents and non-human primates (13)(14)(15). During the acute phase of infection and disease, flavivirus crossneutralizing antibodies can be induced, but these are usually not durable and cross-neutralization is not retained following a few months (12).…”

Section: Classification and Antigenic Relationships Among Flavivirusesmentioning

confidence: 95%

Cross-Reactive Immunity Among Flaviviruses

2020

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Flaviviruses consist of significant human pathogens responsible for hundreds of millions of infections each year. Their antigenic relationships generate immune responses that are cross-reactive to multiple flaviviruses and their widespread and overlapping geographical distributions, coupled with increases in vaccination coverage, increase the likelihood of exposure to multiple flaviviruses. Depending on the antigenic properties of the viruses to which a person is exposed, flavivirus cross-reactivity can be beneficial or could promote immune pathologies. In this review we describe our knowledge of the functional immune outcomes that arise from varied flaviviral immune statuses. The cross-reactive antibody and T cell immune responses that are protective versus pathological are also addressed.

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“…In this group, DENV infection stimulated a higher frequency of these cells, but remarkably, also increased highly cross-reactive IFN-γ-producing CD4 + T cells directed to DENV E, and ZIKV E/NS proteins. A study showed that cross-reactive ZIKV-primed CD4 + T cells 73 . On the other hand, we showed that naïve animals with DENV de novo response did not cross-neutralized ZIKV at all, which state that although similar, antigenic differences are sufficient to mount predominantly type-specific rather than crossreactive responses during a primary infection 50,55 .…”

Section: Higher Proportion Of Ifn-γ and Tnf-α Producing T Cells Beformentioning

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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Flavivirus serocomplex cross-reactive immunity is protective by activating heterologous memory CD4 T cells

Abstract: Sequential exposures to flaviviruses sharing CD4 epitopes promote protection during subsequent heterologous infections.

Cited by 73 publications

References 67 publications

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

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

Cross-Reactive Immunity Among Flaviviruses

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

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