scholarly journals Homologous Prime-Boost Vaccination with OVA Entrapped in Self-Adjuvanting Archaeosomes Induces High Numbers of OVA-Specific CD8+ T Cells that Protect Against Subcutaneous B16-OVA Melanoma

Vaccines ◽  
2016 ◽  
Vol 4 (4) ◽  
pp. 44 ◽  
Author(s):  
Felicity Stark ◽  
Michael McCluskie ◽  
Lakshmi Krishnan
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Boost Vaccination

scholarly journals Airway delivery of both a BCG prime and adenoviral boost drives CD4 and CD8 T cells into the lung tissue parenchyma

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Daryan A. Kaveh ◽  
M. Carmen Garcia-Pelayo ◽  
Naomi C. Bull ◽  
Pedro J. Sanchez-Cordon ◽  
John Spiropoulos ◽  
...  
Keyword(s):  
T Cells ◽  
Lung Tissue ◽  
Cd8 T Cells ◽  
Murine Model ◽  
Vaccine Development ◽  
Lung Parenchyma ◽  
Boost Vaccination ◽  
Parenteral Delivery ◽  
Promising Strategy ◽  
Intravascular Staining

Abstract Heterologous BCG prime-boost regimens represent a promising strategy for an urgently required improved tuberculosis vaccine. Identifying the mechanisms which underpin the enhanced protection induced by such strategies is one key aim which would significantly accelerate rational vaccine development. Experimentally, airway vaccination induces greater efficacy than parenteral delivery; in both conventional vaccination and heterologous boosting of parenteral BCG immunisation. However, the effect of delivering both the component prime and boost immunisations via the airway is not well known. Here we investigate delivery of both the BCG prime and adenovirus boost vaccination via the airway in a murine model, and demonstrate this approach may be able to improve the protective outcome over parenteral prime/airway boost. Intravascular staining of T cells in the lung revealed that the airway prime regimen induced more antigen-specific multifunctional CD4 and CD8 T cells to the lung parenchyma prior to challenge and indicated the route of both prime and boost to be critical to the location of induced resident T cells in the lung. Further, in the absence of a defined phenotype of vaccine-induced protection to tuberculosis; the magnitude and phenotype of vaccine-specific T cells in the parenchyma of the lung may provide insights into potential correlates of immunity.

scholarly journals Cross-competition of CD8+ T cells shapes the immunodominance hierarchy during boost vaccination

2007 ◽  
Vol 204 (9) ◽  
pp. 2187-2198 ◽  
Author(s):  
Wolfgang Kastenmuller ◽  
Georg Gasteiger ◽  
Julian H. Gronau ◽  
Robert Baier ◽  
Ronny Ljapoci ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Antigen Expression ◽  
Infection Model ◽  
Cell Responses ◽  
Boost Vaccination ◽  
Antigen Presenting ◽  
Virus Infection Model ◽  
Cross Competition

CD8+ T cell responses directed against multiple pathogen-derived epitopes are characterized by defined immunodominance hierarchy patterns. A possible explanation for this phenomenon is that CD8+ T cells of different specificities compete for access to epitopes on antigen-presenting cells, and that the outcome of this so-called cross-competition reflects the number of induced T cells. In our study using a vaccinia virus infection model, we found that T cell cross-competition is highly relevant during boost vaccination, thereby shaping the immunodominance hierarchy in the recall. We demonstrate that competition was of no importance during priming and was unaffected by the applied route of immunization. It strongly depended on the timing of viral antigen expression in infected APCs, and it was characterized by poor proliferation of T cells recognizing epitopes derived from late viral proteins. To our knowledge, this is the first demonstration of the functional importance of T cell cross-competition during a viral infection. Our findings provide a basis for novel strategies for how boost vaccination to defined antigens can be selectively improved. They give important new insights into the design of more efficient poxviral vectors for immunotherapy.

scholarly journals Rapid and stable mobilization of fully functional spike-specific CD8+ T cells preceding a mature humoral response after SARS-CoV-2 mRNA vaccination

2021 ◽  
Author(s):  
Robert Thimme ◽  
Valerie Oberhardt ◽  
Hendrik Luxenburger ◽  
Janine Kemming ◽  
Isabel Schulien ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Adaptive Immunity ◽  
Cd8 T Cells ◽  
Neutralizing Antibodies ◽  
Memory T Cells ◽  
Natural Infection ◽  
Cd8 T Cell ◽  
Effector Memory ◽  
Boost Vaccination

Abstract SARS-CoV-2 spike mRNA vaccines mediate protection from severe disease as early as 10 days post prime vaccination, when specific antibodies are hardly detectable and still lack neutralizing activity. Vaccine-induced T cells, especially CD8+ T cells, may thus be the main mediators of protection at this early stage. The details of antigen-specific CD8+ T cell induction after prime/boost vaccination, their comparison to naturally induced CD8+ T cell responses and their association with other arms of vaccine-induced adaptive immunity remain, however, incompletely understood. Here, we show on a single epitope level that both, a stable memory precursor pool of spike-specific CD8+ T cells and fully functional spike-specific effector CD8+ T cell populations, are vigorously mobilized as early as one week after prime vaccination when CD4+ T cell and spike-specific antibody responses are still weak and neutralizing antibodies are lacking. Boost vaccination after 3 weeks induced a full-fledged recall expansion generating highly differentiated CD8+ effector T cells, however, neither the functional capacity nor the memory precursor T cell pool was affected. Compared to natural infection, vaccine-induced early memory T cells exhibited similar frequencies and functional capacities but a different subset distribution dominated by effector memory T cells at the expense of self-renewing and multipotent central memory T cells. Our results indicate that spike-specific CD8+ T cells may represent the major correlate of early protection after SARS-CoV-2 mRNA/bnt162b2 prime vaccination that precede other effector arms of vaccine-induced adaptive immunity and are stably maintained after boost vaccination.

scholarly journals Heterologous Prime-Boost Vaccination with a Peptide-Based Vaccine and Viral Vector Reshapes Dendritic Cell, CD4+ and CD8+ T Cell Phenotypes to Improve the Antitumor Therapeutic Effect

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6107
Author(s):  
Tamara Hofer ◽  
Matteo Rossi ◽  
Susanna Carboni ◽  
Wilma Di Berardino Besson ◽  
Dorothee von Laer ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Lymph Nodes ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Viral Vector ◽  
Mouse Tumor ◽  
Protein Vaccine ◽  
Boost Vaccination ◽  
Draining Lymph Nodes

Heterologous prime-boost settings with a protein vaccine and the viral vector vesicular stomatitis virus, both expressing tumor-associated antigens (KISIMA-TAA and VSV-GP-TAA), have been previously shown to generate potent antitumor immunity. In the cold TC-1 model (HPV antigen) and the immune-infiltrate MC-38 model (Adpgk, Reps1 and Rpl18 neo-antigens), we further investigated pivotal immune cells that educate CD8+ T cells. Heterologous prime-boost vaccination induced a superior antitumor response characterized by the increase in number and functionality of antigen-specific CD8+ T cells, recruitment of cross-presenting dendritic cells, and polarization of CD4+ T cells towards an antitumor Th1 phenotype within the tumor and tumor-draining lymph nodes, turning the cold TC-1 tumor into a hot, inflamed tumor. In the inflamed MC-38 tumor model, treatment combination markedly prolonged the overall survival of mice. Treatment with multi-epitope vaccines also induced high frequencies of multiple antigen specificities in the periphery and in the tumor. Prime-boost treatment reduced tumor-infiltrating regulatory CD4+ T cells whilst increasing cross-presenting dendritic cells in tumor-draining lymph nodes. In conclusion, heterologous prime-boost vaccination possesses the ability to induce a potent anti-tumor response in both immune-excluded and immune-infiltrated mouse tumor models. Additionally, this study highlights the design of a multi-epitope vaccine for cancer immunotherapy.

Combined HDAC and BET inhibition to enhance cancer vaccine-elicited T-cell responses.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14632-e14632
Author(s):  
Alexander Badamchi-Zadeh ◽  
Kelly Dare Moynihan ◽  
Nicholas M Provine ◽  
Rafael Larocca ◽  
Darrell J Irvine ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Ductal Adenocarcinoma ◽  
Cell Responses ◽  
Boost Vaccination ◽  
Immunological Mechanisms ◽  
Ifn Γ

e14632 Background: The combined inhibition of histone deacetylases (HDAC) and the proteins of the bromo and extra terminal (BET) family have recently shown therapeutic efficacy against pancreatic ductal adenocarcinoma, melanoma and lymphoma cancers in murine studies. However, in these studies the role of the immune system in therapeutically controlling these cancers was not explored. Methods: We sought to investigate the effect of the HDAC inhibitor romidepsin (RMD) and the BET inhibitor I-BET151, both singly and in combination, on vaccine elicited immune responses. C57Bl/6 mice were immunized with differing vaccines (Adenoviral, protein) in prime-boost regimens, under treatment with RMD, I-BET151, or RMD+I-BET151. Results: The combination RMD+I-BET151, administered during Adenoviral prime-boost vaccination, resulted in the significant increase in the frequency and number of antigen-specific CD8 T cells. RMD+I-BET151 treatment affected vaccine-elicited secondary T cell responses, significantly increasing the frequency of IFN-γ+ splenic CD8 T cells and maintaining their dual IFN-γ+TNFa+ polyfunctionality. These CD8 T cells maintained their protective ability against Listeria monocytogenes, and protected against B16-OVA challenge. The significant augmentation of vaccine elicited CD8 T cell responses under RMD+I-BET151 treatment was additionally observed following protein (OVA+CpG) prime-boost vaccination, resulting in greater protection against B16-OVA challenge and enhanced survival. T-regulatory cell (FoxP3+CD4+) frequency and total CD4 and CD8 cell numbers remained unaltered following RMD+I-BET151 treatment. Conclusions: Combined HDAC and BET inhibition resulted in greater vaccine-elicited CD8 T cell responses following immunization by multiple vaccine platforms, and enhanced protection against B16-OVA challenges. We are currently assessing immunological mechanisms of action for this combined HDAC and BET inhibition.

scholarly journals LFA-1 Mediates Cytotoxicity and Tissue Migration of Specific CD8+ T Cells after Heterologous Prime-Boost Vaccination against Trypanosoma cruzi Infection

2017 ◽  
Vol 8 ◽  
Author(s):  
Camila Pontes Ferreira ◽  
Leonardo Moro Cariste ◽  
Fernando Dos Santos Virgílio ◽  
Barbara Ferri Moraschi ◽  
Caroline Brandão Monteiro ◽  
...  
Keyword(s):  
T Cells ◽  
Trypanosoma Cruzi ◽  
Cd8 T Cells ◽  
Boost Vaccination ◽  
Tissue Migration ◽  
Cruzi Infection

scholarly journals Recombinant BCG-Prime and DNA-Boost Immunization Confers Mice with Enhanced Protection against Mycobacterium kansasii

Vaccines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1260
Author(s):  
Shihoko Komine-Aizawa ◽  
Satoru Mizuno ◽  
Kazuhiro Matsuo ◽  
Takahiro Namiki ◽  
Satoshi Hayakawa ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Multidrug Resistant ◽  
Mycobacterium Kansasii ◽  
Booster Immunization ◽  
Boost Vaccination ◽  
Antigen 85B ◽  
Boost Immunization ◽  
Potential Alternative ◽  
Mouse Lungs

The incidence of infections with nontuberculous mycobacteria (NTM) has been increasing worldwide. The emergence of multidrug-resistant NTM is a serious clinical concern, and a vaccine for NTM has not yet been developed. We previously developed a new recombinant Bacillus Calmette–Guérin (rBCG) vaccine encoding the antigen 85B (Ag85B) protein of Mycobacterium kansasii—termed rBCG-Mkan85B—which was used together with a booster immunization with plasmid DNA expressing the same M. kansasii Ag85B gene (DNA-Mkan85B). We reported that rBCG-Mkan85B/DNA-Mkan85B prime–boost immunization elicited various NTM strain-specific CD4+ and CD8+ T cells and induced Mycobacterium tuberculosis-specific immunity. In this study, to investigate the protective effect against M. kansasii infection, we challenged mice vaccinated with a rBCG-Mkan85B or rBCG-Mkan85B/DNA-Mkan85B prime–boost strategy with virulent M. kansasii. Although BCG and rBCG-Mkan85B immunization each suppressed the growth of M. kansasii in the mouse lungs, the rBCG-Mkan85B/DNA-Mkan85B prime–boost vaccination reduced the bacterial burden more significantly. Moreover, the rBCG-Mkan85B/DNA-Mkan85B prime–boost vaccination induced antigen-specific CD4+ and CD8+ T cells. Our data suggest that rBCG-Mkan85B/DNA-Mkan85B prime–boost vaccination effectively enhances antigen-specific T cells. Our novel rBCG could be a potential alternative to clinical BCG for preventing various NTM infections.

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