Human Cytotoxic T Lymphocyte Responses to Live Attenuated 17D Yellow Fever Vaccine: Identification of HLA-B35-Restricted CTL Epitopes on Nonstructural Proteins NS1, NS2b, NS3, and the Structural Protein E

Co, Mary Dawn T.; Terajima, Masanori; Cruz, John; Ennis, Francis A.; Rothman, Alan L.

doi:10.1006/viro.2001.1255

Cited by 98 publications

(86 citation statements)

References 56 publications

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“…The results presented herein suggest that E is the most immunogenic WNV protein (Fig. 2) and reactivity to two peptides from E (E [17][18][19][20][21][22][23][24][25][26] and E 430 -438 ) dominated the CD8 ϩ T cell response in 40% of our cohort (Fig. 7).…”

Section: Discussionmentioning

confidence: 75%

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The Memory T Cell Response to West Nile Virus in Symptomatic Humans following Natural Infection Is Not Influenced by Age and Is Dominated by a Restricted Set of CD8+ T Cell Epitopes

Parsons

Lelic

Hayes

et al. 2008

The Journal of Immunology

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We examined the West Nile virus (WNV)-specific T cell response in a cohort of 52 patients with symptomatic WNV infections, including neuroinvasive and non-invasive disease. Although all virus proteins were shown to contain T cell epitopes, certain proteins, such as E, were more commonly targeted by the T cell response. Most patients exhibited reactivity toward 3–4 individual WNV peptides; however, several patients exhibited reactivity toward >10 individual peptides. The relative hierarchy of T cell reactivities in all patients showed a fixed pattern that was sustained throughout the 12-mo period of the current study. Surprisingly, we did not observe any relationship between age and either the breadth or magnitude of the T cell response following infection. We also did not observe a relationship between disease severity and either the breadth or magnitude of the T cell response. The T cell epitopes were distributed in a non-random fashion across the viral polyprotein and a limited number of epitopes appeared to dominate the CD8+ T cell response within our cohort. These data provide important new insight into the T cell response against WNV in humans.

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Section: Discussionmentioning

confidence: 75%

“…Likewise, a study of four volunteers immunized with the yellow fever virus vaccine demonstrated CTL reactivity against E, NS1, NS2A, NS2B, and NS3 (25). Thus, it is clear that the CD8 ϩ T cell response following flavivirus infection targets against both structural and non-structural proteins.…”

Section: Discussionmentioning

confidence: 99%

The Memory T Cell Response to West Nile Virus in Symptomatic Humans following Natural Infection Is Not Influenced by Age and Is Dominated by a Restricted Set of CD8+ T Cell Epitopes

Parsons

Lelic

Hayes

et al. 2008

The Journal of Immunology

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“…We generated HLA/peptide tetramers for the three SNV epitopes presented by HLA-B*3501, and a negative control tetramer using an epitope in the yellow fever virus (YFV) NS1 protein that is presented by HLA-B*3501 (28). The specificity of each tetramer was confirmed by flow cytometry using SNV-and YFV-specific CD8 ϩ CTL lines, and by staining PBMC from an HLA-B3501 ϩ individual with no known exposure to either SNV or YFV (Fig.…”

Section: Quantitation Of Snv-specific Cd8 ϩ T Cells In Pbmc Samplesmentioning

confidence: 99%

Role of Specific CD8+ T Cells in the Severity of a Fulminant Zoonotic Viral Hemorrhagic Fever, Hantavirus Pulmonary Syndrome

Kilpatrick¹,

Terajima²,

Koster

et al. 2004

The Journal of Immunology

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154

174

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We report on the role of specific CD8+ T cells in the pathogenesis of a highly lethal human viral disease, hantavirus pulmonary syndrome (HPS). HPS is a zoonotic disease caused by transmission of Sin Nombre virus (SNV) from chronically infected deer mice. In humans, this fulminant infection is characterized by lung capillary leakage, respiratory failure, and cardiogenic shock. Individuals with HLA-B*3501 have an increased risk of developing severe HPS, suggesting that CD8+ T cell responses to SNV contribute to pathogenesis. We identified three CD8+ T cell epitopes in SNV presented by HLA-B*3501 and quantitated circulating SNV-specific CD8+ T cells in 11 acute HPS patients using HLA/peptide tetramers. We found significantly higher frequencies of SNV-specific T cells in patients with severe HPS requiring mechanical ventilation (up to 44.2% of CD8+ T cells) than in moderately ill HPS patients hospitalized but not requiring mechanical ventilation (up to 9.8% of CD8+ T cells). These results imply that virus-specific CD8+ T cells contribute to HPS disease outcome. Intense CD8+ T cell responses to SNV may be induced by the encounter of the unnatural human host to this zoonotic virus without coevolution. This may also be the immunopathologic basis of other life-threatening human virus infections.

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“…Co et al [8] identified specific cytotoxic T cells against epitopes on non-structural proteins NS1, NS2b, NS3 and structural protein E of the 17D vaccine virus, which are induced early at day 14 post-vaccination and maintained for 18 months.…”

Section: Introductionmentioning

confidence: 99%

Activation/modulation of adaptive immunity emerges simultaneously after 17DD yellow fever first-time vaccination: is this the key to prevent severe adverse reactions following immunization?

Martins

Silva

Marciano

et al. 2007

Clinical and Experimental Immunology

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SummaryOver past decades the 17DD yellow fever vaccine has proved to be effective in controlling yellow fever and promises to be a vaccine vector for other diseases, but the cellular and molecular mechanisms by which it elicits such broadbased immunity are still unclear. In this study we describe a detailed phenotypic investigation of major and minor peripheral blood lymphocyte subpopulations aimed at characterizing the kinetics of the adaptive immune response following primary 17DD vaccination. Our major finding is a decreased frequency of circulating CD19+ cells at day 7 followed by emerging activation/modulation phenotypic features (CD19 + and CD8 + cells further support this hypothesis. We hypothesize that this controlled microenviroment seems to be the key to prevent the development of serious adverse events, and even deaths, associated with the 17DD vaccine reported in the literature.

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Human Cytotoxic T Lymphocyte Responses to Live Attenuated 17D Yellow Fever Vaccine: Identification of HLA-B35-Restricted CTL Epitopes on Nonstructural Proteins NS1, NS2b, NS3, and the Structural Protein E

Cited by 98 publications

References 56 publications

The Memory T Cell Response to West Nile Virus in Symptomatic Humans following Natural Infection Is Not Influenced by Age and Is Dominated by a Restricted Set of CD8+ T Cell Epitopes

The Memory T Cell Response to West Nile Virus in Symptomatic Humans following Natural Infection Is Not Influenced by Age and Is Dominated by a Restricted Set of CD8+ T Cell Epitopes

Role of Specific CD8+ T Cells in the Severity of a Fulminant Zoonotic Viral Hemorrhagic Fever, Hantavirus Pulmonary Syndrome

Activation/modulation of adaptive immunity emerges simultaneously after 17DD yellow fever first-time vaccination: is this the key to prevent severe adverse reactions following immunization?

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