scholarly journals Evaluation of Toll-Like Receptor 11 Agonist Adjuvant Activity in Immunization of BALB/c Mice with Total Lysate Antigens of Toxoplasma gondii RH Strain

2020 ◽  
Author(s):  
Meysam SHOKRI ◽  
Khosro HAZRATI TAPPEH ◽  
Elyar MESHKINI ◽  
Arash AMINPOUR
Keyword(s):  
Toxoplasma Gondii ◽  
Immune Responses ◽  
Survival Time ◽  
Vaccine Candidate ◽  
Significant Protection ◽  
Toll Like Receptor ◽  
Adjuvant Activity ◽  
Proliferation Of Lymphocytes ◽  
Lysate Antigens ◽  
Total Lysate

Background: In this study, the effect of total lysate antigen (TLA) of Toxoplasma gondii on spleen lymphocyte prolifration, secretion of IL5, INF-γ, and mice survival time was evaluated using agonist of toll-like receptor (TLR) 11, as an adjuvant. Results: Mice immunized with TLA + adjuvant showed higher immunization index than the two other groups and combination of TLR11 (as an adjuvant) and TLA significantly elevated the effect of TLA by increasing the production of INF-γ and IL-5 and by the shift of the immune system to Th1. In addition, the combination of TLA and TLR11 adjuvant increased the proliferation of lymphocytes and survival time in mice against T. gondii. Conclusion: Profilin (as an adjuvant) in combination with TLA could be a potent vaccine candidate that evokes a powerful specific immune response and significantly improves the efficacy of TLA vaccine by increasing the induction of INF-γ production and by shifting the immune responses to Th1 profile through increasing the INF-γ/IL-5 ratio. It causes significant protection against T. gondii after i.p. injection.

scholarly journals An Intranasally Delivered Toll-Like Receptor 7 Agonist Elicits Robust Systemic and Mucosal Responses to Norwalk Virus-Like Particles

2010 ◽  
Vol 17 (12) ◽  
pp. 1850-1858 ◽  
Author(s):  
Lissette S. Velasquez ◽  
Brooke E. Hjelm ◽  
Charles J. Arntzen ◽  
Melissa M. Herbst-Kralovetz
Keyword(s):  
Immune Responses ◽  
Immune Protection ◽  
Norwalk Virus ◽  
Toll Like Receptor ◽  
Adjuvant Activity ◽  
Mucosal Adjuvant ◽  
Virus Like Particles ◽  
Vaccine Trials ◽  
Specific Serum ◽  
Tlr7 Agonist

ABSTRACT Norwalk virus (NV) is an enteric pathogen from the genus Norovirus and a major cause of nonbacterial gastroenteritis in humans. NV virus-like particles (VLPs) are known to elicit systemic and mucosal immune responses when delivered nasally; however, the correlates of immune protection are unknown, and codelivery with a safe and immunogenic mucosal adjuvant may enhance protective anti-NV immune responses. Resiquimod (R848), an imidazoquinoline-based Toll-like receptor 7 and/or 8 (TLR7/8) agonist, is being evaluated as an adjuvant in FDA-approved clinical vaccine trials. As such, we evaluated the adjuvant activity of two imidazoquinoline-based TLR7 and TLR7/8 agonists when codelivered intranasally with plant-derived NV VLPs. We also compared the activity of these agonists to the gold standard mucosal adjuvant, cholera toxin (CT). Our results indicate that codelivery with the TLR7 agonist, gardiquimod (GARD), induces NV VLP-specific serum IgG and IgG isotype responses and mucosal IgA responses in the gastrointestinal, respiratory, and reproductive tracts that are superior to those induced by R848 and comparable to those induced by the mucosal adjuvant CT. This study supports the continued investigation of GARD as a mucosal adjuvant for NV VLPs and possible use for other VLP-based vaccines for which immune responses at distal mucosal sites (e.g., respiratory and reproductive tracts) are desired.

scholarly journals Immunization With a DNA Vaccine Encoding the Toxoplasma gondii’ s GRA39 Prolongs Survival and Reduce Brain Cyst Formation in a Murine Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuchao Zhu ◽  
Yanan Xu ◽  
Lu Hong ◽  
Chunxue Zhou ◽  
Jia Chen
Keyword(s):  
Toxoplasma Gondii ◽  
Immune Responses ◽  
Survival Time ◽  
Protective Efficacy ◽  
Serum Antibody ◽  
Cyst Formation ◽  
Dna Immunization ◽  
Genotype I ◽  
Significant Difference ◽  
Cellular Immune

Toxoplasma gondii, an obligate intracellular protozoan parasite, can cause infect almost all warm-blooded animals and humans. To evaluate the immunogenicity and protective efficacy of T. gondii GRA39 (TgGRA39) in mice by using DNA immunization, we constructed a recombinant eukaryotic plasmid pVAX-TgGRA39. The specific immune responses in immunized mice were analyzed by serum antibody and cytokine measurements, lymphocyte proliferation assays and flow cytometry of T lymphocyte subclasses. Also, protective efficacy against acute and chronic T. gondii infection was assessed by observing the survival time after challenge with the highly virulent T. gondii RH strain (Genotype I) and counting the number of cyst-forming in brain at 4 weeks post-infection with the cyst-forming PRU strain of T. gondii (Genotype II), respectively. Our results showed that DNA immunization with pVAX-GRA39 via intramuscular injection three times, at 2-week intervals could elicit humoral and cellular immune response, indicated by enhanced levels of IgG and IgG2a antibodies (a slightly elevated IgG2a to IgG1 ratio), and increased levels of cytokines IFN-γ, IL-2, IL-12, IL-17A, IL-17F, IL-22 and IL-23 and percentages of CD3+ CD4+ CD8- and CD3+ CD8+ CD4– T cells, in contrast to non-immunized mice. The significant increase in the expression levels of IL-6, TGF-β1, IL-1β, and the transcription factor factors RORγt, RORα, and STAT3 involved in the activation and pathway of Th17 and Tc17 cells, were also observed. However, no significant difference was detected in level of IL-4 and IL-10 (p > 0.05). These effective immune responses had mounted protective immunity against T. gondii infection, with a prolonged survival time (16.80 ± 3.50 days) and reduced cyst numbers (44.5%) in comparison to the control mice. Our data indicated that pVAX-TgGRA39 could induce effective humoral, and Th1-type, Th17, and Tc17 cellular immune responses, and may represent a promising vaccine candidate against both acute and chronic T. gondii infection.

scholarly journals Safety and immunogenicity of an mRNA-lipid nanoparticle vaccine candidate against SARS-CoV-2

2021 ◽  
Author(s):  
Peter G. Kremsner ◽  
Philipp Mann ◽  
Arne Kroidl ◽  
Isabel Leroux-Roels ◽  
Christoph Schindler ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vaccine Candidate ◽  
Phase 1 ◽  
Lipid Nanoparticles ◽  
Enzyme Linked Immunosorbent Assay ◽  
Receptor Binding Domain ◽  
Igg Antibodies ◽  
Phase 1 Study ◽  
S Protein ◽  
Dosage Escalation

Summary Background We used the RNActive® technology platform (CureVac N.V., Tübingen, Germany) to prepare CVnCoV, a COVID-19 vaccine containing sequence-optimized mRNA coding for a stabilized form of SARS-CoV‑2 spike (S) protein encapsulated in lipid nanoparticles (LNP). Methods This is an interim analysis of a dosage escalation phase 1 study in healthy 18–60-year-old volunteers in Hannover, Munich and Tübingen, Germany, and Ghent, Belgium. After giving 2 intramuscular doses of CVnCoV or placebo 28 days apart we assessed solicited local and systemic adverse events (AE) for 7 days and unsolicited AEs for 28 days after each vaccination. Immunogenicity was measured as enzyme-linked immunosorbent assay (ELISA) IgG antibodies to SARS-CoV‑2 S‑protein and receptor binding domain (RBD), and SARS-CoV‑2 neutralizing titers (MN50). Results In 245 volunteers who received 2 CVnCoV vaccinations (2 μg, n = 47, 4 μg, n = 48, 6 μg, n = 46, 8 μg, n = 44, 12 μg, n = 28) or placebo (n = 32) there were no vaccine-related serious AEs. Dosage-dependent increases in frequency and severity of solicited systemic AEs, and to a lesser extent local AEs, were mainly mild or moderate and transient in duration. Dosage-dependent increases in IgG antibodies to S‑protein and RBD and MN50 were evident in all groups 2 weeks after the second dose when 100% (23/23) seroconverted to S‑protein or RBD, and 83% (19/23) seroconverted for MN50 in the 12 μg group. Responses to 12 μg were comparable to those observed in convalescent sera from known COVID-19 patients. Conclusion In this study 2 CVnCoV doses were safe, with acceptable reactogenicity and 12 μg dosages elicited levels of immune responses that overlapped those observed in convalescent sera.

scholarly journals Essential role of IRAK-4 protein and its kinase activity in Toll-like receptor–mediated immune responses but not in TCR signaling

2007 ◽  
Vol 204 (5) ◽  
pp. 1013-1024 ◽  
Author(s):  
Tatsukata Kawagoe ◽  
Shintaro Sato ◽  
Andreas Jung ◽  
Masahiro Yamamoto ◽  
Kosuke Matsui ◽  
...  
Keyword(s):  
Immune Responses ◽  
Kinase Activity ◽  
Interleukin 1 ◽  
Cell Receptor ◽  
Nuclear Factor Κb ◽  
Toll Like Receptor ◽  
Tcr Signaling ◽  
Mitogen Activated Protein

Interleukin-1 receptor–associated kinase 4 (IRAK-4) was reported to be essential for the Toll-like receptor (TLR)– and T cell receptor (TCR)–mediated signaling leading to the activation of nuclear factor κB (NF-κB). However, the importance of kinase activity of IRAK family members is unclear. In this study, we investigated the functional role of IRAK-4 activity in vivo by generating mice carrying a knockin mutation (KK213AA) that abrogates its kinase activity. IRAK-4KN/KN mice were highly resistant to TLR-induced shock response. The cytokine production in response to TLR ligands was severely impaired in IRAK-4KN/KN as well as IRAK-4−/− macrophages. The IRAK-4 activity was essential for the activation of signaling pathways leading to mitogen-activated protein kinases. TLR-induced IRAK-4/IRAK-1–dependent and –independent pathways were involved in early induction of NF-κB–regulated genes in response to TLR ligands such as tumor necrosis factor α and IκBζ. In contrast to a previous paper (Suzuki, N., S. Suzuki, D.G. Millar, M. Unno, H. Hara, T. Calzascia, S. Yamasaki, T. Yokosuka, N.J. Chen, A.R. Elford, et al. 2006. Science. 311:1927–1932), the TCR signaling was not impaired in IRAK-4−/− and IRAK-4KN/KN mice. Thus, the kinase activity of IRAK-4 is essential for the regulation of TLR-mediated innate immune responses.

Innate immune responses to toll-like receptor stimulation are altered during the course of pregnancy

2018 ◽  
Vol 128 ◽  
pp. 30-37 ◽  
Author(s):  
Susanne Maria Ziegler ◽  
Cai Niklaas Feldmann ◽  
Sven Hendrik Hagen ◽  
Laura Richert ◽  
Tanja Barkhausen ◽  
...  
Keyword(s):  
Immune Responses ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Toll Like Receptor ◽  
Receptor Stimulation
Sign in / Sign up

Export Citation Format

Share Document