scholarly journals Using Adjuvants to Drive T Cell Responses for Next-Generation Infectious Disease Vaccines

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 820
Author(s):  
Rekha R. Rapaka ◽  
Alan S. Cross ◽  
Monica A. McArthur
Keyword(s):  
T Cell ◽  
Cell Function ◽  
T Cell Responses ◽  
Antigen Delivery ◽  
T Helper ◽  
Vaccine Responses ◽  
Cell Responses ◽  
Vaccine Antigens ◽  
Technological Challenge ◽  
Antigen Presenting

Using adjuvants to drive features of T cell responses to vaccine antigens is an important technological challenge in the design of new and improved vaccines against infections. Properties such as T helper cell function, T cell memory, and CD8+ T cell cytotoxicity may play critical roles in optimal and long-lived immunity through vaccination. Directly manipulating specific immune activation or antigen delivery pathways with adjuvants may selectively augment desired T cell responses in vaccination and may improve the effectiveness and durability of vaccine responses in humans. In this review we outline recently studied adjuvants in their potential for antigen presenting cell and T cell programming during vaccination, with an emphasis on what has been observed in studies in humans as available.

Soluble CD30 and Lymphocyte Activation Gene-3 (CD223), as Potential Serological Markers of T Helper-Type Cytokine Response Induced by Acellular Pertussis Vaccine

2006 ◽  
Vol 19 (1) ◽  
pp. 205873920601900 ◽  
Author(s):  
C. M. Ausiello ◽  
R. Palazzo ◽  
F. Spensieri ◽  
F. Urbani ◽  
M. Massari ◽  
...  
Keyword(s):  
T Cell ◽  
Pertussis Vaccine ◽  
Lymphocyte Activation ◽  
T Cell Responses ◽  
Serological Markers ◽  
T Helper ◽  
Cell Responses ◽  
Soluble Cd30 ◽  
Vaccine Antigens ◽  
Lymphocyte Activation Gene

T cell responses are involved in vaccine-induced immunity to pertussis but no easy-to-monitor, serological markers are available to assess these responses. The lymphocyte activation gene-3 (CD223) molecule is present on, and released by, activated T helper (Th) 1 cells, whereas CD30 molecules have been associated with Th2 immune responses. Starting from the recent knowledge of the cytokine profile induced by pertussis vaccination, we examined the levels of soluble (s)CD223 and sCD30 proteins in child recipients of acellular pertussis (aP) and diphtheria-tetanus (DT) vaccines and in children receiving DT vaccine only, as control. The correlation of the two proteins with specific antibody and T cell responses was assessed. The main findings are: i) sCD223 and sCD30 levels are inversely related, suggesting that the two markers are the expression of different and counter-regulated T-cell responses; ii) sCD30 level correlated with induction of T cell proliferation to pertussis vaccine antigens and antibody response to pertussis toxin. Overall, sCD30 and sCD223 levels seem to be promising candidate markers to assess the induction of Th-type responses in vaccine recipients.

Aspergillus fumigatus suppresses the human cellular immune response via gliotoxin-mediated apoptosis of monocytes

Blood ◽  
2005 ◽  
Vol 105 (6) ◽  
pp. 2258-2265 ◽  
Author(s):  
Marta Stanzani ◽  
Enrico Orciuolo ◽  
Russell Lewis ◽  
Dimitrios P. Kontoyiannis ◽  
Sergio L. R. Martins ◽  
...  
Keyword(s):  
T Cell ◽  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Cell Function ◽  
T Cell Responses ◽  
Cell Responses ◽  
Cytokine Flow Cytometry ◽  
Induced Apoptosis ◽  
Antigen Presenting

AbstractAspergillus fumigatus (AF) is a ubiquitous mold and is the most common cause of invasive aspergillosis, an important source of morbidity and mortality in immunocompromised hosts. Using cytokine flow cytometry, we assessed the magnitude of functional CD4+ and CD8+ T-cell responses following stimulation with Aspergillus antigens. Relative to those seen with cytomegalovirus (CMV) or superantigen stimulation, responses to Aspergillus antigens were near background levels. Subsequently, we confirmed that gliotoxin, the most abundant mycotoxin produced by AF, was able to suppress functional T-cell responses following CMV or staphylococcal enterotoxin B (SEB) stimulation. Additional studies demonstrated that crude AF filtrates and purified gliotoxin inhibited antigen-presenting cell function and induced the preferential death of monocytes, leading to a marked decrease in the monocyte-lymphocyte ratio. Analysis of caspase-3 activation confirmed that gliotoxin preferentially induced apoptosis of monocytes; similar effects were observed in CD83+ monocyte-derived dendritic cells. Importantly, the physiologic effects of gliotoxin in vitro were observed below concentrations recently observed in the serum of patients with invasive aspergillosis. These studies suggest that the production of gliotoxin by AF may constitute an important immunoevasive mechanism that is mediated by direct effects on antigen-presenting cells and both direct and indirect effects on T cells.

Antigen-presenting cell function of dendritic cells and macrophages in proliferative T cell responses to soluble and particulate antigens

1986 ◽  
Vol 16 (4) ◽  
pp. 345-350 ◽  
Author(s):  
Martien L. Kapsenberg ◽  
Marcel B. M. Teunissen ◽  
Frank E. M. Stiekema ◽  
Hiskias G. Keizer
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Cell Function ◽  
T Cell Responses ◽  
Antigen Presenting Cell ◽  
Cell Responses ◽  
Antigen Presenting

scholarly journals Extracellular vesicles in human semen modulate antigen-presenting cell function and decrease downstream antiviral T cell responses

PLoS ONE ◽  
2019 ◽  
Vol 14 (10) ◽  
pp. e0223901 ◽  
Author(s):  
Lucia Vojtech ◽  
Mengying Zhang ◽  
Veronica Davé ◽  
Claire Levy ◽  
Sean M. Hughes ◽  
...  
Keyword(s):  
T Cell ◽  
Extracellular Vesicles ◽  
Cell Function ◽  
T Cell Responses ◽  
Human Semen ◽  
Antigen Presenting Cell ◽  
Cell Responses ◽  
Antigen Presenting

scholarly journals STING negatively regulates allogeneic T-cell responses by constraining antigen-presenting cell function

2021 ◽  
Author(s):  
Yongxia Wu ◽  
Chih-Hang Anthony Tang ◽  
Corey Mealer ◽  
David Bastian ◽  
M. Hanief Sofi ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Function ◽  
T Cell Responses ◽  
Antigen Presenting Cell ◽  
Cell Responses ◽  
Antigen Presenting

Stimulation of autologous proliferative and cytotoxic T-cell responses by “leukemic dendritic cells” derived from blast cells in acute myeloid leukemia

Blood ◽  
2001 ◽  
Vol 97 (9) ◽  
pp. 2764-2771 ◽  
Author(s):  
Beth D. Harrison ◽  
Julie A. Adams ◽  
Mark Briggs ◽  
Michelle L. Brereton ◽  
John A. Liu Yin
Keyword(s):  
T Cells ◽  
Acute Myeloid Leukemia ◽  
Dendritic Cells ◽  
T Cell ◽  
Myeloid Leukemia ◽  
T Cell Responses ◽  
Cell Responses ◽  
Antigen Presenting ◽  
Acute Myeloid ◽  
Stimulation Of

Abstract Effective presentation of tumor antigens is fundamental to strategies aimed at enrolling the immune system in eradication of residual disease after conventional treatments. Myeloid malignancies provide a unique opportunity to derive dendritic cells (DCs), functioning antigen-presenting cells, from the malignant cells themselves. These may then co-express leukemic antigens together with appropriate secondary signals and be used to generate a specific, antileukemic immune response. In this study, blasts from 40 patients with acute myeloid leukemia (AML) were cultured with combinations of granulocyte-macrophage colony-stimulating factor, interleukin 4, and tumor necrosis factor α, and development to DCs was assessed. After culture, cells from 24 samples exhibited morphological and immunophenotypic features of DCs, including expression of major histocompatibility complex class II, CD1a, CD83, and CD86, and were potent stimulators in an allogeneic mixed lymphocyte reaction (MLR). Stimulation of autologous T-cell responses was assessed by the proliferative response of autologous T cells to the leukemic DCs and by demonstration of the induction of specific, autologous, antileukemic cytotoxicity. Of 17 samples, 11 were effective stimulators in the autologous MLR, and low, but consistent, autologous, antileukemic cytotoxicity was induced in 8 of 11 cases (mean, 27%; range, 17%-37%). This study indicates that cells with enhanced antigen-presenting ability can be generated from AML blasts, that these cells can effectively prime autologous cytotoxic T cells in vitro, and that they may be used as potential vaccines in the immunotherapy of AML.

A phase 1b study of personalized neoantigen vaccine plus pembrolizumab in adults with advanced cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2615-2615
Author(s):  
Aaron Miller ◽  
Zeynep Kosaloglu-Yalcin ◽  
Luise Westernberg ◽  
Leslie Montero ◽  
Milad Bahmanof ◽  
...  
Keyword(s):  
T Cell ◽  
Injection Site ◽  
Cell Function ◽  
Injection Site Reaction ◽  
Therapeutic Vaccine ◽  
T Cell Responses ◽  
Patient Specific ◽  
Clinical Activity ◽  
Site Reaction ◽  
Cell Responses

2615 Background: Neoantigens (NeoAg) are key targets for personalized immunotherapy but efficient methods for their systematic identification and therapeutic targeting remain elusive. We developed a methodology to reliably identify and verify somatic alteration-derived neoantigens based on natural T cell responses against them which formed the basis of an individualized therapeutic vaccine strategy. Methods: This is a phase Ib study to assess the immunogenicity, safety and early clinical activity of personalized synthetic long peptides (PSLP) cancer vaccines in combination with pembrolizumab for patients with treatment refractory metastatic solid tumors or PSLP vaccine alone as an adjuvant treatment with patients with no evidence of disease (NED) that incorporates patient-specific NeoAg identified by an HLA-agnostic, functional T-cell assay (see table). Results: At the time of data cutoff, a total of 5 patients had been treated on ARM-A, 5 patients on ARM-C and 2 patients on ARM-D. AES possibly attributed to personalized vaccine (PSLP), or pembrolizumab, or both include: Grade 1: Arthralgia (1); Diarrhea (1); Fever (4); Fatigue (7); Generalized muscle weakness (1); Headache (2); Nausea (1); Confusion (1); Injection site reaction (5); Rash maculo-papular (3); Flu like symptoms (5); Myalgia (1); and Grade 2: Diarrhea (1); Fatigue (1); Hyperhidrosis (1); Hypothyroidism (1); Injection site reaction (1); Proteinuria (1); Renal and Urinary – other (1); and Grade 3: Colitis (1). For the 9 patients with at least 1 radiographic assessment at the time of analysis 6 had a best response of stable disease (SD) and 3 had progressive disease (PD). Immune monitoring of peripheral blood specimens consistently demonstrated that NeoAg-specific T cell responses were enhanced following administration of PSLP vaccine. On-treatment biopsies demonstrated immune-editing with the variant allele frequency of targeted mutations decreasing following administration of the PSLP vaccine. Conclusions: Taken together, these data meet the trial primary endpoint by demonstrating PSLP vaccines targeting NeoAg identified using the HLA-agnostic pipeline augment effector T cell function against these targets. Clinical trial information: NCT02287428. [Table: see text]

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