Seeking Flavivirus Cross-Protective Immunity

Franco, Lorrany dos Santos; Gushi, Letícia Tsieme; Luiz, Wilson Barros; Amorim, Jaime Henrique

doi:10.3389/fimmu.2019.02260

Cited by 23 publications

(32 citation statements)

References 61 publications

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“…indicated that, following heterologous DENV infection, memory CD8 + T cells expanded that recognized conserved NS proteins (33). In fact, NS3 and NS5 represent the main targets of the CD8 + T cell response to flaviviruses (34, 35). One study reported more cross-reactive T cell responses to full length NS3 helicase, because of higher sequence homology, than that to the protease region alone (36).…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

“…In a mouse model, CD8 + T cells can mediate protection against ZIKV (35). DENV-specific cross-reactive CD8 + T cells can also protect (38), and similar responses are detected in humans, where cross-reactive CD8 + T cells specific for DENV display anti-ZIKV effector potential toward ZIKV, mediating direct cytolysis (39).…”

Section: Discussionmentioning

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

View full text Add to dashboard Cite

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“…Various subsets of T cells are essential for efficient infection clearance and for the development of robust antibody responses against flaviviruses. Flavivirus reactive T cell epitopes have been identified in both viral structural and non-structural proteins and for CD8 and CD4 T cells (14,29). Often, we expect that the T cell epitope must be 100% conserved to induce recall of a memory T cell from a previous infection; however, similar epitopes with only minor substitutions often are able to activate T cells as well although with potentially differing degrees of responses (30,31).…”

Section: Flavivirus Cross-reactive T Cell Responsesmentioning

confidence: 99%

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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“…Epitopes in the E protein that are recognized by neutralizing antibodies reside in the ectodomain portion consisting of DI, DII, and DIII (Fibriansah and Lok, 2016;Dos Santos Franco et al, 2019;Li et al, 2019). Therefore, it is a surprise that a single amino acid substitution at residue 408 within the EH1 domain, downstream of DIII, dramatically reduced the PS180 neutralizing Viremia of Pekin duckling after inoculation with rPS-F408L and rPS.…”

Section: Discussionmentioning

confidence: 99%