Cell-mediated immunity induced by chimeric tetravalent dengue vaccine in naive or flavivirus-primed subjects

Guy, Bruno; Nougarede, Nolwenn; Begue, Sarah; Sanchez, Violette; Souag, Nadia; Carre, Murielle; Chambonneau, Laurent; Morrisson, Dennis N.; Shaw, David R.; Qiao, Ming; Dumas, Rafaele; Lang, Jean; Forrat, Rémi

doi:10.1016/j.vaccine.2008.08.019

Cited by 127 publications

(96 citation statements)

References 25 publications

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“…In previous clinical trials we sought to detect IL-4, and detected none. 19 IFNγ and TNFα secretion by CD8 + T cells in response to YF-17D NS3, increased after vaccination in both age groups, as seen previously, 19 and IFNγ dominated, again in support of vaccine safety. These responses persisted over time, but were not boosted by the second or third vaccinations.…”

Section: Discussionsupporting

confidence: 77%

“…As understanding CMI in children is of particular interest in the case of dengue, 19 we adapted two complementary assays to using smaller sample volumes by using whole blood instead of purified PBMCs in the antigenic stimulation step of the ICS assay, and using freshly purified, rather than thawed PBMCs in the multiplex assay. This required that a laboratory close to the clinical site perform the stimulation of whole blood samples and freshly purified PBMCs, which in turn required that samples be collected in the morning to allow fresh blood to be simulated for 5 h. Due to school, morning study visits proved unfeasible for adolescents and instead adolescent participants were recruited in the afternoon and samples were processed the next day.…”

Section: Discussionmentioning

confidence: 99%

“…[13][14][15][16][17][18] We have previously shown that CYD-TDV vaccination in adults induces significant CD8 + T-cell responses against the YF-17D backbone of the CYD vaccine viruses and T helper 1 (Th1) responses to each dengue serotype without inducing changes in serum pro-inflammatory cytokines. 19 Here we expand on these investigations and report on cellular responses up to one year after CYD-TDV vaccination of a cohort of adolescents and adults recruited in a dengue low endemic area. One of our objectives was to assess the feasibility of evaluating CMI responses using small volumes of blood.…”

Section: Introductionmentioning

confidence: 97%

“…It was demonstrated in human recipients of live attenuated dengue vaccine candidate (VDV1 and VDV2) that the cytokine pattern induced upon live or inactivated vaccine in vitro restimulation was very similar, suggesting a CD4 helper response specific for structural proteins. 19 By intracellular cytokine staining, the CD4 and CD8 response against the NS3 protein of either wildtype dengue or the YF-17D vaccine virus were analyzed, allowing the differentiation of the memory response against CYD-TDV and wild-type virus in the same subject, since no cross-reactivity between DENV and YF-17D NS3 was previously demonstrated. 19 …”

Section: Introductionmentioning

confidence: 99%

“…19 By intracellular cytokine staining, the CD4 and CD8 response against the NS3 protein of either wildtype dengue or the YF-17D vaccine virus were analyzed, allowing the differentiation of the memory response against CYD-TDV and wild-type virus in the same subject, since no cross-reactivity between DENV and YF-17D NS3 was previously demonstrated. 19 …”

Section: Introductionmentioning

confidence: 99%

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Persistence of Th1/Tc1 responses one year after tetravalent dengue vaccination in adults and adolescents in Singapore

Harenberg

Begue

Mamessier

et al. 2013

Human Vaccines & Immunotherapeutics

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Persistence of Th1/Tc1 responses one year after tetravalent dengue vaccination in adults and adolescents in Singapore

Harenberg

Begue

Mamessier

et al. 2013

Human Vaccines & Immunotherapeutics

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Multifunctional T cell response in convalescent patients two years after ZIKV infection

Neto

Gonçalves-Pereira

Queiroz

et al. 2020

Journal of Leukocyte Biology

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Zika is an important emerging infectious disease in which the role of T cells remains elusive. This study aimed to evaluate the phenotype of multifunctional T cells in individuals 2 yr after exposure to Zika virus (ZIKV). We used a library of 671 synthetic peptides covering the whole polyprotein of ZIKV in pools corresponding to each viral protein (i.e., capsid, membrane precursor or prM, envelope, NS1 [nonstructural protein], NS2A + NS2B, NS3, NS4A + NS4B, and NS5) to stimulate PBMCs from individuals previously exposed to ZIKV. We observed an increased frequency of ZIKV-specific IFN , IL-17A, TNF, and IL-10 production by T cell populations. IFN and TNF production were especially stimulated by prM, capsid, or NS1 in CD8+ T cells and by capsid or prM in CD4+ T cells. In addition, there was an increase in the frequency of IL-10+ CD8+ T cells after stimulation with prM, capsid, NS1, NS3, or NS5. Multifunctional properties were observed in ZIKVspecific T cells responding especially to prM, capsid, NS1 or, to a smaller extent, NS3 antigens. For example, we found a consistent IFN + TNF+ CD8+ T cell population in response to most virus antigens and CD4+ and CD8+ T cells that were IFN + IL-17A+ and IL-17A+IL-10+, which could also produce TNF, in response to capsid, prM, NS1, or NS3 stimulation. Interestingly, CD8+ T cells were more prone to a multifunctional phenotype than CD4+ T cells, and multifunctional T cells were more efficient at producing cytokines than single-function cells. This work provides relevant insights into the quality of ZIKV-specific T cell responses and ZIKV immunity. K E Y W O R D S immunity, multifunctional T cells, Zika, ZIKV 1 INTRODUCTION Zika virus (ZIKV) is an arbovirus of the Flaviviridae family and Flavivirus genus that comprises more than 70 viruses distributed worldwide, among which approximately 40 viruses are described as causing diseases in humans. 1 Among the Flavivirus viruses of particular interest, Abbreviations: CZS, Congenital Zika syndrome; DENV, Dengue virus; MFI, mean fluorescence intensity; NS, nonstructural protein; prM, membrane precursor; Tc, CD8+ cytotoxic T cell; YFV, Yellow fever virus; ZIKV, Zika virus. the most prominent members are dengue virus (DENV), responsible for an annual incidence of 96 million infections with symptomatic dengue fever; yellow fever virus (YFV); West Nile virus (WNV); Japanese encephalitis virus (JEV); and ZIKV, which are classified as emerging infectious viruses. 1 It is estimated that only 20-25% of ZIKV-infected individuals develop symptoms, with nonspecific clinical manifestations common to other arboviruses, 2 such as rash, low-grade fever, nonpurulent conjunctivitis, myalgia, and arthritis/arthralgia, which are usually benign and self-limiting. ZIKV infection has also been associated with

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Recombinant, Chimeric, Live, Attenuated Vaccines Against Flaviviruses and Alphaviruses

Monath¹

2010

Replicating Vaccines

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Many arthropod-borne flaviviruses are important human pathogens responsible for diverse illnesses, including yellow fever (YF), Japanese encephalitis (JE), and TBE and dengue. Live, attenuated vaccines have afforded the most effective and economical means of prevention and control, as illustrated by YF 17D and JE SA14-14-2 vaccines. Recent advances in recombinant DNA technology have made it possible to explore a novel approach for developing live attenuated flavivirus vaccines against other flaviviruses. Full-length cDNA clones allow construction of infectious virus bearing attenuating mutations or deletions incorporated in the viral genome. It is also possible to create chimeric flaviviruses in which the structural protein genes for the target antigens of a flavivirus are replaced by the corresponding genes of another flavivirus. By combining these molecular techniques, the DNA sequences of DEN4 containing a deletion in the 3 0 NCR, a DEN2 PDK-53 candidate vaccine and YF 17D vaccine have been used as the genetic backbone to construct chimeric flaviviruses with the required attenuation phenotype and expression of the target antigens. Encouraging results from preclinical and clinical studies have shown that several chimeric flavivirus vaccines have the safety profile and satisfactory immunogenicity and protective efficacy to warrant development as products for human use. The chimeric flavivirus strategy has led to the rapid development of novel live, attenuated vaccines against DEN, TBE, JE and WN. This chapter reviews an extensive body of work on the development of these vaccine candidates, one of which is licensed and others are in advanced clinical development.A similar approach is being used to create vaccines against alphaviruses. Here the experience is less, but some promising data have been developed, particularly using SIN virus as a vector for structural genes of heterologous alphaviruses. The principal issues for this technology will be to achieve convincing nonclinical data on safety, the proper balance of attenuation and immunogenicity, and proof of concept in large animal models and ultimately humans.

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Cell-mediated immunity induced by chimeric tetravalent dengue vaccine in naive or flavivirus-primed subjects

Cited by 127 publications

References 25 publications

Persistence of Th1/Tc1 responses one year after tetravalent dengue vaccination in adults and adolescents in Singapore

Persistence of Th1/Tc1 responses one year after tetravalent dengue vaccination in adults and adolescents in Singapore

Multifunctional T cell response in convalescent patients two years after ZIKV infection

Recombinant, Chimeric, Live, Attenuated Vaccines Against Flaviviruses and Alphaviruses

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