scholarly journals Induction of Humoral and Cellular Immunity by Intradermal Delivery of SARS-CoV-2 Nucleocapsid Protein Using Dissolvable Microneedles

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Chaiyaporn Kuwentrai ◽  
Jinming Yu ◽  
Bao-zhong Zhang ◽  
Ye-fan Hu ◽  
Ying Dou ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
T Lymphocyte ◽  
Cellular Immunity ◽  
Nucleocapsid Protein ◽  
Cytotoxic T Lymphocyte ◽  
Protein A ◽  
Suitable Candidate ◽  
Humoral And Cellular Immunity ◽  
Cell Responses ◽  
Intradermal Delivery

The nucleocapsid protein (NP) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains immunogenic epitopes that can induce cytotoxic T lymphocyte (CTL) against viral infection. This makes the nucleocapsid protein a suitable candidate for developing a vaccine against SARS-CoV-2 infection. This article reports the intradermal delivery of NP antigen using dissolvable microneedle skin patches that could induce both significant B cell and T cell responses.

scholarly journals Human Memory Cytotoxic T-Lymphocyte (CTL) Responses to Hantaan Virus Infection: Identification of Virus-Specific and Cross-Reactive CD8+ CTL Epitopes on Nucleocapsid Protein

1999 ◽  
Vol 73 (7) ◽  
pp. 5301-5308 ◽  
Author(s):  
Heather L. Van Epps ◽  
Connie S. Schmaljohn ◽  
Francis A. Ennis
Keyword(s):  
Amino Acids ◽  
T Cell ◽  
T Lymphocyte ◽  
Nucleocapsid Protein ◽  
Cytotoxic T Lymphocyte ◽  
Human Memory ◽  
Hantaan Virus ◽  
Specific Cell ◽  
Cell Responses ◽  
Lymphocyte Responses

ABSTRACT Hantaan virus, the prototypic member of the Hantavirusgenus, causes hemorrhagic fever with renal syndrome in humans. We examined the human memory T-lymphocyte responses of three donors who had previous laboratory-acquired infections with Hantaan virus. We demonstrated virus-specific responses in bulk cultures of peripheral blood mononuclear cells (PBMC) from all donors. Bulk T-cell responses were directed against either Hantaan virus nucleocapsid (N) or G1 protein, and these responses varied between donors. We established both CD4+ and CD8+ N-specific cell lines from two donors and CD4+ G1-specific cell lines from a third donor. All CD8+ cytotoxic T-lymphocyte (CTL) lines recognized one of two epitopes on the nucleocapsid protein: one epitope spanning amino acids 12 to 20 and the other spanning amino acids 421 to 429. The CTL lines specific for amino acids 12 to 20 were restricted by HLA B51, and those specific for amino acids 421 to 429 were restricted by HLA A1. The N-specific CTL lines isolated from these two donors included both Hantaan virus-specific CTLs and hantavirus cross-reactive CTLs. Responses to both epitopes are detectable in short-term bulk cultures of PBMC from one donor, and precursor frequency analysis confirms that CTLs specific for these epitopes are present at relatively high precursor frequencies in the peripheral T-cell pool. These data suggest that infection with Hantaan virus results in the generation of CTL to limited epitopes on the nucleocapsid protein and that infection also results in the generation of cross-reactive T-cell responses to distantly related hantaviruses which cause the distinct hantavirus pulmonary syndrome. This is the first demonstration of human T-lymphocyte responses to Hantaan virus.

scholarly journals Cytotoxic T-Lymphocyte-Associated Antigen 4 (CTLA-4)- and Programmed Death 1 (PD-1)-Mediated Regulation of Monofunctional and Dual Functional CD4+ and CD8+ T-Cell Responses in a Chronic Helminth Infection

2019 ◽  
Vol 87 (12) ◽  
Author(s):  
Anuradha Rajamanickam ◽  
Saravanan Munisankar ◽  
Chandrakumar Dolla ◽  
Thomas B. Nutman ◽  
Subash Babu
Keyword(s):  
T Cell ◽  
T Lymphocyte ◽  
Helminth Infection ◽  
Cytotoxic T Lymphocyte ◽  
T Cell Responses ◽  
Content Type ◽  
Cell Responses ◽  
Dual Functional ◽  
Programmed Death ◽  
Programmed Death 1

ABSTRACT Chronic helminth infections are known to be associated with the modulation of antigen-specific T-cell responses. Strongyloides stercoralis infection is characterized by the downmodulation of antigen-specific Th1 and Th17 responses and the upregulation of Th2 and Th9 responses. Immune homeostasis is partially maintained by negative regulators of T-cell activation, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1), which dampen effector responses during chronic infections. However, their roles in S. stercoralis infection are yet to be defined. Therefore, we sought to determine the role of CTLA-4 and PD-1 in regulating CD4+ and CD8+ T-cell responses and examined the frequencies of monofunctional and dual functional Th1/T cytotoxic type 1 (Tc1), Th17/Tc17, Th2/Tc2, and Th9/Tc9 cells in S. stercoralis infection in 15 infected individuals stimulated with parasite antigen following CTLA-4 or PD-1 blockade. Our data reveal that CTLA-4 or PD-1 blockade results in significantly enhanced frequencies of monofunctional and dual functional Th1/Tc1 and Th17/Tc17 cells and, in contrast, diminishes the frequencies of monofunctional and dual functional Th2/Tc2 and Th9/Tc9 cells with parasite antigen stimulation in whole-blood cultures. Thus, we demonstrate that CTLA-4 and PD-1 limit the induction of particular T-cell subsets in S. stercoralis infection, which suggests the importance of CTLA-4 and PD-1 in immune modulation in a chronic helminth infection.

scholarly journals Analysis of the HLA-restricted influenza-specific cytotoxic T lymphocyte response in transgenic mice carrying a chimeric human-mouse class I major histocompatibility complex.

1991 ◽  
Vol 173 (4) ◽  
pp. 1007-1015 ◽  
Author(s):  
A Vitiello ◽  
D Marchesini ◽  
J Furze ◽  
L A Sherman ◽  
R W Chesnut
Keyword(s):  
Transgenic Mice ◽  
T Lymphocyte ◽  
Matrix Protein ◽  
Cytotoxic T Lymphocyte ◽  
Dominant Role ◽  
Class I ◽  
Cell Responses ◽  
Histocompatibility Complex ◽  
Restriction Element ◽  
Hla A2.1

Transgenic murine lines have been constructed that express a chimeric class I molecule composed of the alpha 1 and alpha 2 domains of HLA-A2.1 and the alpha 3, transmembrane, and cytoplasmic domains of H-2Kb. Upon immunization with influenza virus, transgenic mice developed a strong A2.1Kb-restricted cytotoxic T lymphocyte (CTL) response specific for the same matrix protein epitope that serves as the dominant A2.1-restricted determinant in the equivalent human response. Fine specificity analysis of CTL clones using truncated peptides revealed strong similarity between the response repertoire of transgenic mice and that previously reported using influenza-specific A2.1-restricted CTL clones from humans. This suggests that even when considering T cell responses by different species, the alpha 1 and alpha 2 domains of the restriction element play a dominant role in determining the CTL specific repertoire. Thus, substituting the alpha 3 domain of A2.1 with a murine counterpart has permitted development of a transgenic strain that should serve as an excellent model system in studies of HLA-restricted responses.

scholarly journals Epstein-Barr Virus-Induced Gene 3 (EBI3) Blocking Leads to Induce Antitumor Cytotoxic T Lymphocyte Response and Suppress Tumor Growth in Colorectal Cancer by Bidirectional Reciprocal-Regulation STAT3 Signaling Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Yanfang Liang ◽  
Qianqian Chen ◽  
Wenjing Du ◽  
Can Chen ◽  
Feifei Li ◽  
...  
Keyword(s):  
Tumor Growth ◽  
T Lymphocyte ◽  
Epstein Barr Virus ◽  
Cytotoxic T Lymphocyte ◽  
Reciprocal Regulation ◽  
Barr Virus ◽  
Cell Responses ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Epstein Barr

Epstein-Barr virus-induced gene 3 (EBI3) is a member of the interleukin-12 (IL-12) family structural subunit and can form a heterodimer with IL-27p28 and IL-12p35 subunit to build IL-27 and IL-35, respectively. However, IL-27 stimulates whereas IL-35 inhibits antitumor T cell responses. To date, little is known about the role of EBI3 in tumor microenvironment. In this study, firstly we assessed EBI3, IL-27p28, IL-12p35, gp130, and p-STAT3 expression with clinicopathological parameters of colorectal cancer (CRC) tissues; then we evaluated the antitumor T cell responses and tumor growth with a EBI3 blocking peptide. We found that elevated EBI3 may be associated with IL-12p35, gp130, and p-STAT3 to promote CRC progression. EBI3 blocking peptide promoted antitumor cytotoxic T lymphocyte (CTL) response by inducing Granzyme B, IFN-γproduction, and p-STAT3 expression and inhibited CRC cell proliferation and tumor growth to associate with suppressing gp130 and p-STAT3 expression. Taken together, these results suggest that EBI3 may mediate a bidirectional reciprocal-regulation STAT3 signaling pathway to assist the tumor escape immune surveillance in CRC.

scholarly journals Chemoimmunotherapy targeting Wilms’ tumor 1 (WT1)-specific cytotoxic T lymphocyte and helper T cell responses for patients with pancreatic cancer

2014 ◽  
Vol 3 (10) ◽  
pp. e958950 ◽  
Author(s):  
Shigeo Koido ◽  
Sadamu Homma ◽  
Masato Okamoto ◽  
Kazuki Takakura ◽  
Jianlin Gong ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
T Cell ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Wilms Tumor ◽  
T Cell Responses ◽  
Helper T Cell ◽  
Cell Responses ◽  
Wilms Tumor 1
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