scholarly journals Nasal Vaccination with a Fusion Protein of Hemagglutinin A Antigenic Region and Maltose-Binding Protein Elicits CD4+ T Cell Responses via Toll-Like Receptor 4

2012 ◽  
Vol 10 (4) ◽  
pp. 255-260
Author(s):  
Yuan Du ◽  
Tomomi Hashizume ◽  
Tomoko Kurita-Ochiai ◽  
Yoshimitsu Abiko ◽  
Takahiro Ikeda ◽  
...  
Keyword(s):  
T Cell ◽  
Fusion Protein ◽  
Binding Protein ◽  
T Cell Responses ◽  
Maltose Binding Protein ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Cell Responses ◽  
Antigenic Region ◽  
Nasal Vaccination

scholarly journals Full-Length Plasmodium falciparum Circumsporozoite Protein Administered with Long-Chain Poly(I·C) or the Toll-Like Receptor 4 Agonist Glucopyranosyl Lipid Adjuvant-Stable Emulsion Elicits Potent Antibody and CD4+T Cell Immunity and Protection in Mice

2012 ◽  
Vol 81 (3) ◽  
pp. 789-800 ◽  
Author(s):  
Kathrin Kastenmüller ◽  
Diego A. Espinosa ◽  
Lauren Trager ◽  
Cristina Stoyanov ◽  
Andres M. Salazar ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Full Length ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Content Type ◽  
E Coli ◽  
Cell Responses ◽  
Cell Immunity ◽  
Antibody Titers

ABSTRACTThePlasmodium falciparumcircumsporozoite (CS) protein (CSP) is a major vaccine target for preventing malaria infection. Thus, developing strong and durable antibody and T cell responses against CSP with novel immunogens and potent adjuvants may improve upon the success of current approaches. Here, we compare four distinct full-lengthP. falciparumCS proteins expressed inEscherichia coliorPichia pastorisfor their ability to induce immunity and protection in mice when administered with long-chain poly(I·C) [poly(I·C)LC] as an adjuvant. CS proteins expressed inE. coliinduced high-titer antibody responses against the NANP repeat region and potent CSP-specific CD4+T cell responses. Moreover,E. coli-derived CS proteins in combination with poly(I·C)LC induced potent multifunctional (interleukin 2-positive [IL-2+], tumor necrosis factor alpha-positive [TNF-α+], gamma interferon-positive [IFN-γ+]) CD4+effector T cell responses in blood, in spleen, and particularly in liver. Using transgenicPlasmodium bergheiexpressing the repeat region ofP. falciparumCSP [Pb-CS(Pf)], we showed that there was a 1- to 4-log decrease in malaria rRNA in the liver following a high-dose challenge and ∼50% sterilizing protection with a low-dose challenge compared to control levels. Protection was directly correlated with high-level antibody titers but not CD4+T cell responses. Finally, protective immunity was also induced using the Toll-like receptor 4 agonist glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE) as the adjuvant, which also correlated with high antibody titers yet CD4+T cell immunity that was significantly less potent than that with poly(I·C)LC. Overall, these data suggest that full-length CS proteins and poly(I·C)LC or GLA-SE offer a simple vaccine formulation to be used alone or in combination with other vaccines for preventing malaria infection.

scholarly journals Patency ofLitomosoides sigmodontisinfection depends on Toll-like receptor 4 whereas Toll-like receptor 2 signalling influences filarial-specific CD4+T-cell responses

Immunology ◽  
2016 ◽  
Vol 147 (4) ◽  
pp. 429-442 ◽  
Author(s):  
Maria B. Rodrigo ◽  
Sandy Schulz ◽  
Vanessa Krupp ◽  
Manuel Ritter ◽  
Katharina Wiszniewsky ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Cell Responses ◽  
Toll Like Receptor 2

scholarly journals The Effect of Different Immunization Cycles of a Recombinant Mucin1-Maltose-Binding Protein Vaccine on T Cell Responses to B16-MUC1 Melanoma in Mice

2020 ◽  
Vol 21 (16) ◽  
pp. 5810
Author(s):  
Hongyue Zhou ◽  
Zenan Zhang ◽  
Guomu Liu ◽  
Mengyu Jiang ◽  
Jingjing Wang ◽  
...  
Keyword(s):  
T Cell ◽  
Binding Protein ◽  
T Cell Responses ◽  
Maltose Binding Protein ◽  
T Cell Subsets ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protein Vaccine ◽  
Mucin 1 ◽  
Cell Responses ◽  
Immunosuppressive Cells

We explored the effect of a recombinant mucin1-maltose-binding protein vaccine, including immunization cycles of recombinant mucin1-maltose-binding protein (MUC1-MBP) and CpG 2006 on T cell responses to human MUC1-overexpressing mouse melanoma B16 cells (B16-MUC1) melanoma in mice. We found that the vaccine had a significant antitumor effect, with the most obvious tumor-suppressive effect being observed in mice immunized five times. After more than five immunizations, the tumor inhibition rate decreased from 81.67% (five immunizations) to 43.67% (eight immunizations). To study the possible mechanism, Mucin-1(MUC1)-specific antibodies, IFN-γ secretion by lymphocytes, and cytotoxic T lymphocyte (CTL) cytotoxicity were measured by enzyme-linked immunosorbent assay (ELISA) and a real-time cell analyzer (RTCA). T cell subsets and immunosuppressive cells in the mouse spleen and tumor microenvironment were analyzed by FACS. These results showed that five immunizations activated MUC1-specific Th1 and CTL and reduced the ratio of myeloid-derived suppressor cells (MDSCs) and Th17 in mice more significantly than eight immunizations, indicating that excessive frequency of the immune cycle leads to the increased numbers of immunosuppressive cells and decreased numbers of immunostimulatory cells, thereby inhibiting antitumor immune activity. This data provide an experimental foundation for the clinical application of a recombinant MUC1-MBP vaccine.

scholarly journals GLA-SE, a Synthetic Toll-like Receptor 4 Agonist, Enhances T-Cell Responses to Influenza Vaccine in Older Adults

2011 ◽  
Vol 205 (3) ◽  
pp. 466-473 ◽  
Author(s):  
Hayedeh Behzad ◽  
Anke L. W. Huckriede ◽  
Laura Haynes ◽  
Beth Gentleman ◽  
Krysta Coyle ◽  
...  
Keyword(s):  
Older Adults ◽  
T Cell ◽  
Influenza Vaccine ◽  
T Cell Responses ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Cell Responses

Evidence for a Role of TGF-β-Activated Kinase 1 and MAP3K7 Binding Protein 3 in Peanut-Specific T-Cell Responses

2019 ◽  
Vol 179 (1) ◽  
pp. 10-16 ◽  
Author(s):  
Aziza Saidova ◽  
Merima Bublin ◽  
Klara Schmidthaler ◽  
Veronika Fajgelj ◽  
Florian Klinglmueller ◽  
...  
Keyword(s):  
T Cell ◽  
Binding Protein ◽  
T Cell Responses ◽  
Cell Responses

scholarly journals Cold-Inducible RNA Binding Protein as a Vaccination Platform to Enhance Immunotherapeutic Responses against Hepatocellular Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3397
Author(s):  
Leyre Silva ◽  
Josune Egea ◽  
Lorea Villanueva ◽  
Marta Ruiz ◽  
Diana Llopiz ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cell ◽  
Rna Binding ◽  
Checkpoint Inhibitors ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
T Cell Responses ◽  
Tumor Infiltrating Lymphocytes ◽  
Cell Responses ◽  
Tlr4 Ligand

Therapies based on immune checkpoint inhibitors (ICPI) have yielded promising albeit limited results in patients with hepatocellular carcinoma (HCC). Vaccines have been proposed as combination partners to enhance response rates to ICPI. Thus, we analyzed the combined effect of a vaccine based on the TLR4 ligand cold-inducible RNA binding protein (CIRP) plus ICPI. Mice were immunized with vaccines containing ovalbumin linked to CIRP (OVA-CIRP), with or without ICPI, and antigen-specific responses and therapeutic efficacy were tested in subcutaneous and orthotopic mouse models of liver cancer. OVA-CIRP elicited polyepitopic T-cell responses, which were further enhanced when combined with ICPI (anti-PD-1 and anti-CTLA-4). Combination of OVA-CIRP with ICPI enhanced ICPI-induced therapeutic responses when tested in subcutaneous and intrahepatic B16-OVA tumors, as well as in the orthotopic PM299L HCC model. This effect was associated with higher OVA-specific T-cell responses in the periphery, although many tumor-infiltrating lymphocytes still displayed an exhausted phenotype. Finally, a new vaccine containing human glypican-3 linked to CIRP (GPC3-CIRP) induced clear responses in humanized HLA-A2.01 transgenic mice, which increased upon combination with ICPI. Therefore, CIRP-based vaccines may generate anti-tumor immunity to enhance ICPI efficacy in HCC, although blockade of additional checkpoint molecules and immunosuppressive targets should be also considered.

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