scholarly journals T Cell Predominant Response to AAV-Spike Protects hACE2 Mice from SARS-CoV-2 Pneumonia

2021 ◽  
Author(s):  
Christopher D Greer ◽  
Coral M Kasden ◽  
Leon Morales ◽  
Kendall A Lundgreen ◽  
Philip D Hicks ◽  
...  
Keyword(s):  
T Cell ◽  
Humoral Immunity ◽  
Cellular Immunity ◽  
Ex Vivo ◽  
Cytotoxic T Cell ◽  
Effective Vaccine ◽  
Cell Reactivity ◽  
T Cell Infiltration ◽  
T Cell Reactivity

Prevention of COVID-19 is widely believed to depend on neutralization of SARS-CoV-2 by vaccine-induced humoral immunity, raising concern that emerging escape variants may perpetuate the pandemic. Here we show that a single intramuscular injection of Adeno-Associated Virus-6 (AAV6) or AAV9 encoding a modified, N-terminal domain deleted spike protein induces robust cellular immunity and provides long-term protection in k18-hACE2 transgenic mice from lethal SARS-CoV-2 challenge, associated weight loss and pneumonia independent of vaccine-induced neutralizing humoral immunity. In both mice and macaques, vaccine-induced cellular immunity results in the clearance of transduced muscle fibers coincident with macrophage and CD8+ cytotoxic T cell infiltration at the site of immunization. Additionally, mice demonstrate a strong Type-1 polarized cellular immunophenotype and equivalent ex vivo T cell reactivity to peptides of wt and alpha (B.1.1.7) variant spike. These studies demonstrate not only that AAV6 and AAV9 can function as effective vaccine platforms, but also that vaccines can provide long-term efficacy primarily through the induction of cellular immunity. The findings may provide an alternative approach to containment of the evolving COVID-19 pandemic and have broader implications for the development of variant-agnostic universal vaccines against a wider range of pathogens.

scholarly journals 345 PERSISTENT HEPATITIS C VIRUS (HCV) INFECTION IMPAIRS HCV-SPECIFIC CYTOTOXIC T CELL REACTIVITY THROUGH Mcl-1/Bim IMBALANCE DUE TO CD127 DOWN-REGULATION

2013 ◽  
Vol 58 ◽  
pp. S143-S144
Author(s):  
J.R. Larrubia ◽  
M.U. Lokhande ◽  
S. García-Garzón ◽  
J. Miquel ◽  
A. González-Praetorious ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Hcv Infection ◽  
Cytotoxic T Cell ◽  
Down Regulation ◽  
Cell Reactivity ◽  
T Cell Reactivity

Cytotoxic T cell reactivity and HLA-B35 binding of the variantPlasmodium falciparum circumsporozoite protein CD8+ CTL epitope in naturally exposed Kenyan adults

1997 ◽  
Vol 27 (8) ◽  
pp. 1952-1957 ◽  
Author(s):  
Venkatachalam Udhayakumar ◽  
John M. Ongecha ◽  
Ya-Ping Shi ◽  
Michael Aidoo ◽  
A. S. S. Orago ◽  
...  
Keyword(s):  
T Cell ◽  
Circumsporozoite Protein ◽  
Cytotoxic T Cell ◽  
Cell Reactivity ◽  
Ctl Epitope ◽  
T Cell Reactivity

Dissection of anti-CTLA4-induced cytotoxic T-cell responses in melanoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9078-9078
Author(s):  
John B. A. G. Haanen ◽  
Pia Kvistborg ◽  
Daisy Philips ◽  
Sander Kelderman ◽  
Bianca Heemskerk ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Cytotoxic T Cell ◽  
Clinical Activity ◽  
Immune Reactivity ◽  
Cell Detection ◽  
Cell Reactivity ◽  
Cell Responses ◽  
Cytotoxic T Cell Responses ◽  
T Cell Reactivity

9078 Background: There is strong evidence that melanoma-reactive T cells induced by immunotherapeutic interventions such as anti-CTLA4 therapy can exert clinically effects. However, there is very little information on how these therapies influence tumor-specific T cell responses. Furthermore, as the number of potential melanoma-associated antigens to which these responses can be directed is very high, classical strategies to map cytotoxic T cell reactivity do not suffice. Knowledge of such reactivities would be useful to design targeted strategies, selectively aiming to induce immune reactivity against these antigens. Methods: We have addressed these issues by designing MHC class I molecules occupied with UV-sensitive ‘conditional’ ligands, thereby allowing the production of very large collections of pMHC complexes for T cell detection. Secondly, we have developed a ‘combinatorial coding’ strategy that allows parallel detection of dozens of different T cell populations within a single sample. The combined use of MHC ligand exchange and combinatorial coding allows the high-throughput dissection of disease- and therapy-induced CTL immunity. We have used this platform to monitor immune reactivity against a panel of 145 melanoma-associated epitopes in patients receiving Ipilimumab treatment. Results: Comparison of PBMC samples from 32 melanoma patients pre- and post-therapy indicated a significant increase in the number of detectable melanoma-associated T cell responses (p=0.004). Furthermore, kinetic data on T cell responses during therapy suggests that this broadening generally occurs within weeks after start of therapy. The magnitude of melanoma-specific T cell responses that was detectable prior to start of therapy was not significantly altered (p=0.8). Conclusions: These results establish the pattern of melanoma-specific T-cell reactivity induced by anti-CTLA4 treatment and form a benchmark for evaluation of other immunotherapeutic interventions, like anti-PD1 treatment, that are currently undergoing clinical evaluation. Furthermore, our data suggests that the clinical activity of Ipilimumab may be mostly due to epitope spreading, rather than through enhancement of pre-existing immune activity.

scholarly journals Automatic Generation of Validated Specific Epitope Sets

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Sebastian Carrasco Pro ◽  
John Sidney ◽  
Sinu Paul ◽  
Cecilia Lindestam Arlehamn ◽  
Daniela Weiskopf ◽  
...  
Keyword(s):  
T Cell ◽  
Web Application ◽  
Ex Vivo ◽  
Automatic Generation ◽  
Cell Reactivity ◽  
Cell Responses ◽  
Novel Method ◽  
T Cell Reactivity ◽  
Categorization System ◽  
Immune Epitope Database

Accurate measurement of B and T cell responses is a valuable tool to study autoimmunity, allergies, immunity to pathogens, and host-pathogen interactions and assist in the design and evaluation of T cell vaccines and immunotherapies. In this context, it is desirable to elucidate a method to select validated reference sets of epitopes to allow detection of T and B cells. However, the ever-growing information contained in the Immune Epitope Database (IEDB) and the differences in quality and subjects studied between epitope assays make this task complicated. In this study, we develop a novel method to automatically select reference epitope sets according to a categorization system employed by the IEDB. From the sets generated, three epitope sets (EBV, mycobacteria and dengue) were experimentally validated by detection of T cell reactivityex vivofrom human donors. Furthermore, a web application that will potentially be implemented in the IEDB was created to allow users the capacity to generate customized epitope sets.

scholarly journals Spontaneous Cytotoxic T-Cell Reactivity against Indoleamine 2,3-Dioxygenase-2

2011 ◽  
Vol 71 (6) ◽  
pp. 2038-2044 ◽  
Author(s):  
Rikke Bæk Sørensen ◽  
Tania Køllgaard ◽  
Rikke Sick Andersen ◽  
Joost Huibert van den Berg ◽  
Inge Marie Svane ◽  
...  
Keyword(s):  
T Cell ◽  
Cytotoxic T Cell ◽  
Cell Reactivity ◽  
Indoleamine 2,3 Dioxygenase ◽  
T Cell Reactivity

scholarly journals Development and Validation of a Bordetella pertussis Whole-Genome Screening Strategy

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Ricardo da Silva Antunes ◽  
Lorenzo G. Quiambao ◽  
Aaron Sutherland ◽  
Ferran Soldevila ◽  
Sandeep Kumar Dhanda ◽  
...  
Keyword(s):  
T Cell ◽  
Bordetella Pertussis ◽  
Whooping Cough ◽  
Ex Vivo ◽  
Screening Strategy ◽  
Cell Reactivity ◽  
Genome Screening ◽  
T Cell Reactivity ◽  
Development And Validation ◽  
Genomic Map

The immune response elicited by the protective whole-cell pertussis (wP) versus the less-protective acellular pertussis (aP) vaccine has been well characterized; however, important clinical problems remain unsolved, as the inability of the currently administered aP vaccine is resulting in the reemergence of clinical disease (i.e., whooping cough). Strong evidence has shown that original, childhood aP and wP priming vaccines provide a long-lasting imprint on the CD4+ T cells that impacts protective immunity. However, aP vaccination might prevent disease but not infection, which might also affect the breadth of responses to Bordetella pertussis (BP) antigens. Thus, characterizing and defining novel targets associated with T cell reactivity are of considerable interest. Here, we compare the T cell reactivity of original aP and wP priming for different antigens contained or not contained in the aP vaccine and define the basis of a full-scale genomic map of memory T cell reactivity to BP antigens in humans. Our data show that the original priming after birth with aP vaccines has higher T cell reactivity than originally expected against a variety of BP antigens and that the genome-wide mapping of BP using an ex vivo screening methodology is feasible, unbiased, and reproducible. This could provide invaluable knowledge towards the direction of a new and improved pertussis vaccine design.

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