Detection of T H 1/T H 2 cytokine signatures in yellow fever 17DD first-time vaccinees through ELISpot assay

Santos, Ana Paula dos; Matos, Denise C. S.; Bertho, Álvaro Luiz; Mendonça, Sergio C. F.; Marcovistz, Rugimar

doi:10.1016/j.cyto.2008.02.007

Cited by 35 publications

(21 citation statements)

References 22 publications

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“…We wished, therefore, to determine the cellular source of this early IFN-γ production. YF-17D vaccination in humans induces polyvalent immune responses [4, 8, 9]. We, therefore, investigated the kinetics of production of the two major T H 1/T H 2 cytokines, IFN-γ and IL-4 respectively, in rhesus peripheral blood mononuclear cells (PBMC).…”

Section: Resultsmentioning

confidence: 99%

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CD8+ gamma-delta TCR+ and CD4+ T cells produce IFN-γ at 5–7 days after yellow fever vaccination in Indian rhesus macaques, before the induction of classical antigen-specific T cell responses

Neves

Rudersdorf

Galler

et al. 2010

Vaccine

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The yellow fever 17D (YF-17D) vaccine is one of the most efficacious vaccines developed to date. Interestingly, vaccination with YF-17D induces IFN-γ production early after vaccination (d 5–7) before the development of classical antigen-specific CD8+ and CD4+ T cell responses. Here we investigated the cellular source of this early IFN-γ production. At days 5 and 7 post vaccination activated CD8+ gamma-delta TCR T cells produced IFN-γ and TNF-α. Activated CD4+ T cells produced IFN-γ and TNF-α at day 7 post vaccination. This early IFN-γ production was also induced after vaccination with recombinant YF-17D (rYF-17D), but was not observed after recombinant Adenovirus type 5 (rAd5) vaccination. Early IFN-γ production, therefore, might be an important aspect of yellow fever vaccination.

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Section: Resultsmentioning

confidence: 99%

“…YF-17D stimulates several innate immune responses [4–7], which lead to the induction of efficient acquired immunity, with high titers of neutralizing antibodies and robust CD8 + T cell responses. YF-17D vaccination stimulates both arms of the acquired immune response, inducing lymphocytes that produce T H 1/T H 2 mixed cytokines [8, 9]. …”

Section: Introductionmentioning

confidence: 99%

CD8+ gamma-delta TCR+ and CD4+ T cells produce IFN-γ at 5–7 days after yellow fever vaccination in Indian rhesus macaques, before the induction of classical antigen-specific T cell responses

Neves

Rudersdorf

Galler

et al. 2010

Vaccine

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“…Polyfunctional CD4 ϩ T cells were also detected after vaccination (11). Previous studies have demonstrated that YF vaccination elicits both Th1 and Th2 YFV-specific CD4 ϩ T cell responses in humans (13). Investigations focused on innate immune responses after YF vaccination have highlighted coordinated efforts of both the innate and adaptive immune systems in mounting strong immune responses against YFV (14)(15)(16).…”

mentioning

confidence: 88%

Yellow Fever Vaccination Elicits Broad Functional CD4 ⁺ T Cell Responses That Recognize Structural and Nonstructural Proteins

James

LaFond

Gates

et al. 2013

J Virol

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bYellow fever virus (YFV) can induce acute, life-threatening disease that is a significant health burden in areas where yellow fever is endemic, but it is preventable through vaccination. The live attenuated 17D YFV strain induces responses characterized by neutralizing antibodies and strong T cell responses. This vaccine provides an excellent model for studying human immunity. While several studies have characterized YFV-specific antibody and CD8 ؉ T cell responses, less is known about YFV-specific CD4 ؉ T cells. Here we characterize the epitope specificity, functional attributes, and dynamics of YFV-specific T cell responses in vaccinated subjects by investigating peripheral blood mononuclear cells by using HLA-DR tetramers. A total of 112 epitopes restricted by seven common HLA-DRB1 alleles were identified. Epitopes were present within all YFV proteins, but the capsid, envelope, NS2a, and NS3 proteins had the highest epitope density. Antibody blocking demonstrated that the majority of YFV-specific T cells were HLA-DR restricted. Therefore, CD4؉ T cell responses could be effectively characterized with HLA-DR tetramers. Ex vivo tetramer analysis revealed that YFV-specific T cells persisted at frequencies ranging from 0 to 100 cells per million that are detectable years after vaccination. Longitudinal analysis indicated that YFV-specific CD4 ؉ T cells reached peak frequencies, often exceeding 250 cells per million, approximately 2 weeks after vaccination. As frequencies subsequently declined, YFV-specific cells regained CCR7 expression, indicating a shift from effector to central memory. Cells were typically CXCR3 positive, suggesting Th1 polarization, and produced gamma interferon and other cytokines after reactivation in vitro. Therefore, YFV elicits robust early effector CD4؉ T cell responses that contract, forming a detectable memory population. Members of the family Flaviviridae such as Yellow fever virus (YFV) are important causes of illness both historically and at present, causing a significant health burden in areas where yellow fever is endemic (1). Yellow fever (YF) produces symptoms ranging from a mild flu-like illness to hemorrhagic fever and organ failure, but infection is preventable through vaccination (2, 3). The YF vaccine uses a live attenuated virus (17D) and is safe and extremely effective, generating robust antibody responses that persist for decades (4, 5). The vaccine is known to elicit neutralizing antibodies and strong T cell responses in nearly all recipients (6, 7). Therefore, the YFV 17D vaccine is an excellent and important model for studying human antiviral immunity. Multiple studies have investigated the attributes and dynamics of CD4 ϩ and CD8 ϩ T cell responses following YF vaccination (8-12). By using a variety of readouts, these studies demonstrated that YFVspecific CD8 ϩ T cell responses are polyfunctional, exhibit distinct surface phenotypic markers, and peak approximately 2 to 4 weeks after vaccination. Blom et al. evaluated both CD4 ϩ and CD8 ϩ T cell responses by examinin...

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“…It is known that this vaccine virus activates different pathways of the innate immune response, which lead to a polyvalent adaptive response. Vaccination induces cytotoxic CD8+ T memory cells, neutralizing antibody production and a mixed T H 1/T H 2 response (Barba-Spaeth et al, 2005; Miller et al, 2005; Querec et al, 2006; Santos et al, 2008). …”

Section: Introductionmentioning

confidence: 99%

Improved genetic stability of recombinant yellow fever 17D virus expressing a lentiviral Gag gene fragment

et al. 2014

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We have previously designed a method to construct viable recombinant Yellow Fever (YF) 17D viruses expressing heterologous polypeptides including part of the Simian Immunodeficiency Virus (SIV) Gag protein. However, the expressed region, encompassing amino acid residues from 45 to 269, was genetically unstable. In this study, we improved the genetic stability of this recombinant YF 17D virus by introducing mutations in the IRES element localized at the 5′ end of the SIV gag gene. The new stable recombinant virus elicited adaptive immune responses similar to those induced by the original recombinant virus. It is, therefore, possible to increase recombinant stability by removing functional motifs from the insert that may have deleterious effects on recombinant YF viral fitness.

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Detection of T H 1/T H 2 cytokine signatures in yellow fever 17DD first-time vaccinees through ELISpot assay

Cited by 35 publications

References 22 publications

CD8+ gamma-delta TCR+ and CD4+ T cells produce IFN-γ at 5–7 days after yellow fever vaccination in Indian rhesus macaques, before the induction of classical antigen-specific T cell responses

CD8+ gamma-delta TCR+ and CD4+ T cells produce IFN-γ at 5–7 days after yellow fever vaccination in Indian rhesus macaques, before the induction of classical antigen-specific T cell responses

Yellow Fever Vaccination Elicits Broad Functional CD4 ⁺ T Cell Responses That Recognize Structural and Nonstructural Proteins

Improved genetic stability of recombinant yellow fever 17D virus expressing a lentiviral Gag gene fragment

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Detection of T H 1/T H 2 cytokine signatures in yellow fever 17DD first-time vaccinees through ELISpot assay

Cited by 35 publications

References 22 publications

CD8+ gamma-delta TCR+ and CD4+ T cells produce IFN-γ at 5–7 days after yellow fever vaccination in Indian rhesus macaques, before the induction of classical antigen-specific T cell responses

CD8+ gamma-delta TCR+ and CD4+ T cells produce IFN-γ at 5–7 days after yellow fever vaccination in Indian rhesus macaques, before the induction of classical antigen-specific T cell responses

Yellow Fever Vaccination Elicits Broad Functional CD4 + T Cell Responses That Recognize Structural and Nonstructural Proteins

Improved genetic stability of recombinant yellow fever 17D virus expressing a lentiviral Gag gene fragment

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Yellow Fever Vaccination Elicits Broad Functional CD4 ⁺ T Cell Responses That Recognize Structural and Nonstructural Proteins