Correction: Recombinant Yellow Fever Viruses Elicit CD8+T Cell Responses and Protective Immunity against Trypanosoma cruzi

Listeria monocytogenes (Lm) infection induces robust CD8 T cell responses, which play a critical role in resolving Lm during primary infection and provide protective immunity to re-infections. Comprehensive studies have been conducted to delineate the CD8 T cell response after Lm infection. In this review, the generation of the CD8 T cell response to Lm infection will be discussed. The role of dendritic cell subsets in acquiring and presenting Lm antigens to CD8 T cells and the events that occur during T cell priming and activation will be addressed. CD8 T cell expansion, differentiation and contraction as well as the signals that regulate these processes during Lm infection will be explored. Finally, the formation of memory CD8 T cell subsets in the circulation and in the intestine will be analyzed. Recently, the study of CD8 T cell responses to Lm infection has begun to shift focus from the intravenous infection model to a natural oral infection model as the humanized mouse and murinized Lm have become readily available. Recent findings in the generation of CD8 T cell responses to oral infection using murinized Lm will be explored throughout the review. Finally, CD8 T cell-mediated protective immunity against Lm infection and the use of Lm as a vaccine vector for cancer immunotherapy will be highlighted. Overall, this review will provide detailed knowledge on the biology of CD8 T cell responses after Lm infection that may shed light on improving rational vaccine design.

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Protection against Vaccinia Virus Challenge by CD8 Memory T Cells Resolved by Molecular Mimicry

Journal of Virology ◽

10.1128/jvi.01280-06 ◽

2006 ◽

Vol 81 (2) ◽

pp. 934-944 ◽

Cited By ~ 28

Author(s):

Markus Cornberg ◽

Brian S. Sheridan ◽

Frances M. Saccoccio ◽

Michael A. Brehm ◽

Liisa K. Selin

Keyword(s):

T Cells ◽

T Cell ◽

Vaccinia Virus ◽

Cd8 T Cells ◽

Protective Immunity ◽

Molecular Mimicry ◽

T Cell Responses ◽

Cd8 T Cell ◽

T Cell Epitopes ◽

Cell Responses

ABSTRACT Live vaccinia virus (VV) vaccination has been highly successful in eradicating smallpox. However, the mechanisms of immunity involved in mediating this protective effect are still poorly understood, and the roles of CD8 T-cell responses in primary and secondary VV infections are not clearly identified. By applying the concept of molecular mimicry to identify potential CD8 T-cell epitopes that stimulate cross-reactive T cells specific to lymphocytic choriomeningitis virus (LCMV) and VV, we identified after screening only 115 peptides two VV-specific immunogenic epitopes that mediated protective immunity against VV. An immunodominant epitope, VV-e7r130, did not generate cross-reactive T-cell responses to LCMV, and a subdominant epitope, VV-a11r198, did generate cross-reactive responses to LCMV. Infection with VV induced strong epitope-specific responses which were stable into long-term memory and peaked at the time virus was cleared, consistent with CD8 T cells assisting in the control of VV. Two different approaches, direct adoptive transfer of VV-e7r-specific CD8 T cells and prior immunization with a VV-e7r-expressing ubiquitinated minigene, demonstrated that memory CD8 T cells alone could play a significant role in protective immunity against VV. These studies suggest that exploiting cross-reactive responses between viruses may be a useful tool to complement existing technology in predicting immunogenic epitopes to large viruses, such as VV, leading to a better understanding of the role CD8 T cells play during these viral infections.

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T Cell Responses Induced by Attenuated Flavivirus Vaccination Are Specific and Show Limited Cross-Reactivity with Other Flavivirus Species

Journal of Virology ◽

10.1128/jvi.00089-20 ◽

2020 ◽

Vol 94 (10) ◽

Cited By ~ 8

Author(s):

Alba Grifoni ◽

Hannah Voic ◽

Sandeep Kumar Dhanda ◽

Conner K. Kidd ◽

James D. Brien ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Yellow Fever ◽

T Cell Responses ◽

Cd8 T Cell ◽

Cross Reactivity ◽

Live Attenuated Vaccine ◽

Cell Responses ◽

Attenuated Vaccine ◽

E Protein

ABSTRACT Members of the flavivirus genus share a high level of sequence similarity and often circulate in the same geographical regions. However, whether T cells induced by one viral species cross-react with other related flaviviruses has not been globally addressed. In this study, we tested pools of epitopes derived from dengue (DENV), Zika (ZIKV), Japanese encephalitis (JEV), West Nile (WNV), and yellow fever (YFV) viruses by intracellular cytokine staining (ICS) using peripheral blood mononuclear cells (PBMCs) of individuals naturally exposed to DENV or immunized with DENV (TV005) or YF17D vaccine. CD8 T cell responses recognized epitopes from multiple flaviviruses; however, the magnitude of cross-reactive responses was consistently severalfold lower than those to the autologous epitope pools and was associated with lower expression of activation markers such as CD40L, CD69, and CD137. Next, we characterized the antigen sensitivity of short-term T cell lines (TCL) representing 29 different individual epitope/donor combinations. TCL derived from DENV monovalent vaccinees induced CD8 and CD4 T cells that cross-reacted within the DENV serocomplex but were consistently associated with >100-fold-lower antigen sensitivity for most other flaviviruses, with no cross-recognition of YFV-derived peptides. CD8 and CD4 TCL from YF17D vaccinees were associated with very limited cross-reactivity with any other flaviviruses and in five out of eight cases >1,000-fold-lower antigen sensitivity. Overall, our data suggest limited cross-reactivity for both CD4 and CD8 T cell responses between flaviviruses and have implications for understanding immunity elicited by natural infection and strategies to develop live attenuated vaccines against flaviviral species. IMPORTANCE The envelope (E) protein is the dominant target of neutralizing antibodies for dengue virus (DENV) and yellow fever virus (YFV). Accordingly, several DENV vaccine constructs use the E protein in a live attenuated vaccine format, utilizing a backbone derived from a heterologous flavivirus (such as YF) as a delivery vector. This backbone comprises the nonstructural (NS) and capsid (C) antigens, which are dominant targets of T cell responses. Here, we demonstrate that cross-reactivity at the level of T cell responses among different flaviviruses is very limited, despite high levels of sequence homology. Thus, the use of heterologous flavivirus species as a live attenuated vaccine vector is not likely to generate optimal T cell responses and might thus impair vaccine performance.

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Faculty Opinions recommendation of Human effector and memory CD8+ T cell responses to smallpox and yellow fever vaccines.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1108892.567141 ◽

2008 ◽

Author(s):

Holden Maecker

Keyword(s):

T Cell ◽

Yellow Fever ◽

T Cell Responses ◽

Cd8 T Cell ◽

Cell Responses ◽

Memory Cd8 T Cell

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CD8+ T-Cell Responses to Trypanosoma cruzi Are Highly Focused on Strain-Variant trans-Sialidase Epitopes

PLoS Pathogens ◽

10.1371/journal.ppat.0020077 ◽

2006 ◽

Vol 2 (8) ◽

pp. e77 ◽

Cited By ~ 162

Author(s):

Diana L Martin ◽

D. Brent Weatherly ◽

Susana A Laucella ◽

Melissa A Cabinian ◽

Matthew T Crim ◽

...

Keyword(s):

T Cell ◽

Trypanosoma Cruzi ◽

T Cell Responses ◽

Cd8 T Cell ◽

Cell Responses

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Impaired Innate Immunity in Tlr4−/− Mice but Preserved CD8+ T Cell Responses against Trypanosoma cruzi in Tlr4-, Tlr2-, Tlr9- or Myd88-Deficient Mice

PLoS Pathogens ◽

10.1371/journal.ppat.1000870 ◽

2010 ◽

Vol 6 (4) ◽

pp. e1000870 ◽

Cited By ~ 42

Author(s):

Ana-Carolina Oliveira ◽

Bruna C. de Alencar ◽

Fanny Tzelepis ◽

Weberton Klezewsky ◽

Raquel N. da Silva ◽

...

Keyword(s):

Innate Immunity ◽

T Cell ◽

Trypanosoma Cruzi ◽

T Cell Responses ◽

Cd8 T Cell ◽

Cell Responses ◽

Deficient Mice

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The Combined Deficiency of Immunoproteasome Subunits Affects Both the Magnitude and Quality of Pathogen- and Genetic Vaccination-Induced CD8+ T Cell Responses to the Human Protozoan Parasite Trypanosoma cruzi

PLoS Pathogens ◽

10.1371/journal.ppat.1005593 ◽

2016 ◽

Vol 12 (4) ◽

pp. e1005593 ◽

Cited By ~ 8

Author(s):

Jonatan Ersching ◽

José R. Vasconcelos ◽

Camila P. Ferreira ◽

Braulia C. Caetano ◽

Alexandre V. Machado ◽

...

Keyword(s):

T Cell ◽

Trypanosoma Cruzi ◽

T Cell Responses ◽

Protozoan Parasite ◽

Cd8 T Cell ◽

Cell Responses ◽

Combined Deficiency

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The importance of the immunodominant CD8+ T cell epitope of Plasmodium berghei circumsporozoite protein in parasite- and vaccine-induced protection

10.1101/2020.04.03.024539 ◽

2020 ◽

Author(s):

Matthew P. Gibbins ◽

Katja Müller ◽

Maya Glover ◽

Jasmine Liu ◽

Elyzana D. Putrianti ◽

...

Keyword(s):

T Cell ◽

Plasmodium Berghei ◽

Protective Immunity ◽

Significant Proportion ◽

T Cell Responses ◽

Cd8 T Cell ◽

Circumsporozoite Protein ◽

Surface Coat ◽

Class I Mhc ◽

Cell Responses

ABSTRACTThe circumsporozoite protein (CSP) builds up the surface coat of sporozoites and is the leading malaria pre-erythrocytic-stage vaccine candidate. CSP has been shown to induce robust CD8+ T cell responses that are capable of eliminating developing parasites in hepatocytes resulting in protective immunity. In this study, we characterised the importance of the immunodominant CSP-derived epitope, SYIPSAEKI, of Plasmodium berghei in both sporozoite- and vaccine-induced protection in murine infection models. In BALB/c mice, where SYIPSAEKI is efficiently presented in the context of the major histocompatibility complex class I (MHC-I) molecule H-2-Kd, we established that epitope-specific CD8+ T cell responses contribute to parasite killing following sporozoite immunisation. Yet, sterile protection was achieved in the absence of this epitope substantiating the concept that other antigens can be sufficient for parasite-induced protective immunity. Furthermore, we demonstrated that SYIPSAEKI-specific CD8+ T cell responses elicited by viral-vectored CSP-expressing vaccines effectively targeted parasites in hepatocytes. The resulting sterile protection strictly relied on the expression of SYIPSAEKI. In C57BL/6 mice, which are unable to present the immunodominant epitope, CSP-based vaccines did not confer complete protection, despite the induction of high levels of CSP-specific antibodies. These findings underscore the significance of CSP in protection against malaria pre-erythrocytic stages and demonstrate that a significant proportion of the protection against the parasite is mediated by CD8+ T cells specific for the immunodominant CSP-derived epitope.

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