scholarly journals STING Agonist Combined to a Protein-Based Cancer Vaccine Potentiates Peripheral and Intra-Tumoral T Cell Immunity

2021 ◽  
Vol 12 ◽  
Author(s):  
Matteo Rossi ◽  
Susanna Carboni ◽  
Wilma Di Berardino-Besson ◽  
Erika Riva ◽  
Marie-Laure Santiago-Raber ◽  
...  
Keyword(s):  
T Cell ◽  
Cancer Vaccines ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Mouse Tumor ◽  
Therapeutic Vaccination ◽  
Protein Vaccine ◽  
T Cell Infiltration ◽  
Cell Immunity ◽  
Interferon Gene

Combining different immunotherapy approaches is currently building the future of immunotherapy, with the view to maximize anti-tumoral efficacy for larger patient population. The KISIMA™ platform allows the development of protein-based cancer vaccines able to induce tumor-specific T cell response resulting in anti-tumoral efficacy in various mouse models. Intra-tumoral administration of stimulator of interferon gene agonists (STINGa) was shown to induce a potent inflammatory response leading to the development of tumor-specific immunity. Here, we explored the efficacy and mechanisms of action of subcutaneous STINGa treatment combined with therapeutic vaccination in various mouse tumor models. This combinatory treatment highly enhanced frequency and effector function of both peripheral and intra-tumoral antigen-specific CD8 T cells, promoting potent IFNγ and TNFα production along with increased cytotoxicity. Moreover, combination therapy favorably modulated the tumor microenvironment by dampening immune-suppressive cells and increasing CD4 T cell infiltration together with their polarization toward Th1 phenotype. Combination with STINGa treatment improved the effect of therapeutic vaccination, resulting in a prolonged control and slower growth of B16-OVA and TC-1 tumors. Altogether, the results presented here highlight the potential of combining STINGa with a therapeutic protein vaccine for cancer treatment.

scholarly journals Factors influencing maternal microchimerism throughout infancy and its impact on infant T cell immunity

2021 ◽  
Author(s):  
Christina Balle ◽  
Agano Kiravu ◽  
Angela Hoffmann ◽  
Anna-Ursula Happel ◽  
Sami B. Kanaan ◽  
...  
Keyword(s):  
T Cell ◽  
Whole Blood ◽  
T Cell Responses ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Cell Immunity ◽  
Hiv Exposed ◽  
The Impact ◽  
Exposed Uninfected

AbstractDeterminants of the acqusition and maintenance of maternal microchimerism (MMc) during infancy and the impact of MMc on infant immune responses are unknown. We examined factors which influence MMc detection and level across infancy and the effect of MMc on T cell responses to BCG vaccination in a cohort of HIV exposed, uninfected and HIV unexposed infants in South Africa. MMc was measured in whole blood from 58 infants using a panel of quantitative PCR assays at day one and 7, 15, and 36 weeks of life. Infants received BCG at birth, and select whole blood samples from infancy were stimulated in vitro with BCG and assessed for polyfunctional CD4+ T cell responses. MMc was present in most infants across infancy at levels ranging from 1-1,193/100,000 genomic equivalents and was positively impacted by absence of maternal HIV, exclusive breastfeeding, and female sex, emphasizing that both maternal and infant factors may shape the maternal graft. Initiation of maternal antiretroviral therapy prior to pregnancy was associated with partial restoration of MMc in HIV exposed, uninfected infants. Birth MMc was associated with an improved polyfunctional CD4+ T cell response to BCG, suggesting that MMc may functionally impact infant immunity.

scholarly journals SARS-CoV-2-specific T cell memory is long-lasting in the majority of convalsecent COVID-19 individuals

2020 ◽  
Author(s):  
Ziwei Li ◽  
Jing Liu ◽  
Hui Deng ◽  
Xuecheng Yang ◽  
Hua Wang ◽  
...  
Keyword(s):  
T Cell ◽  
Disease Onset ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Long Term Memory ◽  
Memory T Cell ◽  
Cell Responses ◽  
Cell Immunity

ABSTRACTAn unaddressed key question in the current coronavirus disease 2019 (COVID-19) pandemic is the duration of immunity for which specific T cell responses against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are an indispensable element. Being situated in Wuhan where the pandemic initiated enables us to conduct the longest analyses of memory T cell responses against SARS-CoV-2 in COVID-19 convalescent individuals (CIs). Magnitude and breadth of SARS-CoV-2 memory CD4 and CD8 T cell responses were heterogeneous between patients but robust responses could be detected up to 9 months post disease onset in most CIs. Loss of memory CD4 and CD8 T cell responses were observed in only 16.13% and 25.81% of CIs, respectively. Thus, the overall magnitude and breadth of memory CD4 and CD8 T cell responses were quite stable and not inversely correlated with the time from disease onset. Interestingly, the only significant decrease in the response was found for memory CD4 T cells in the first 6-month post COVID-19 disease onset. Longitudinal analyses revealed that the kinetics of SARS-CoV-2 memory CD4 and CD8 T cell responses were quite heterogenous between patients. Loss of memory CD4 T cell responses was observed more frequently in asymptomatic cases than after symptomatic COVID-19. Interestingly, the few CIs in which SARS-CoV-2-specific IgG responses disappeared showed more durable memory CD4 T cell responses than CIs who remained IgG-positive for month. Collectively, we provide the first comprehensive characterization of the long-term memory T cell response in CIs, suggesting that SARS-CoV-2-specific T cell immunity is long-lasting in the majority of individuals.

scholarly journals Intensified and protective CD4+ T cell immunity in mice with anti–dendritic cell HIV gag fusion antibody vaccine

2006 ◽  
Vol 203 (3) ◽  
pp. 607-617 ◽  
Author(s):  
Christine Trumpfheller ◽  
Jennifer S. Finke ◽  
Carolina B. López ◽  
Thomas M. Moran ◽  
Bruno Moltedo ◽  
...  
Keyword(s):  
T Cell ◽  
Recombinant Adenovirus ◽  
Interleukin 2 ◽  
T Cell Response ◽  
T Cell Immunity ◽  
Cd4 T Cell ◽  
Cell Immune Response ◽  
Gag Protein ◽  
Cell Immunity ◽  
Ifn Γ

Current human immunodeficiency virus (HIV) vaccine approaches emphasize prime boost strategies comprising multiple doses of DNA vaccine and recombinant viral vectors. We are developing a protein-based approach that directly harnesses principles for generating T cell immunity. Vaccine is delivered to maturing dendritic cells in lymphoid tissue by engineering protein antigen into an antibody to DEC-205, a receptor for antigen presentation. Here we characterize the CD4+ T cell immune response to HIV gag and compare efficacy with other vaccine strategies in a single dose. DEC-205–targeted HIV gag p24 or p41 induces stronger CD4+ T cell immunity relative to high doses of gag protein, HIV gag plasmid DNA, or recombinant adenovirus-gag. High frequencies of interferon (IFN)-γ– and interleukin 2–producing CD4+ T cells are elicited, including double cytokine-producing cells. In addition, the response is broad because the primed mice respond to an array of peptides in different major histocompatibility complex haplotypes. Long-lived T cell memory is observed. After subcutaneous vaccination, CD4+ and IFN-γ–dependent protection develops to a challenge with recombinant vaccinia-gag virus at a mucosal surface, the airway. We suggest that a DEC-targeted vaccine, in part because of an unusually strong and protective CD4+ T cell response, will improve vaccine efficacy as a stand-alone approach or with other modalities.

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