scholarly journals Mast cell activators: a new class of highly effective vaccine adjuvants

2008 ◽  
Vol 14 (5) ◽  
pp. 536-541 ◽  
Author(s):  
James B McLachlan ◽  
Christopher P Shelburne ◽  
Justin P Hart ◽  
Salvatore V Pizzo ◽  
Rajen Goyal ◽  
...  
Keyword(s):  
Mast Cell ◽  
Effective Vaccine ◽  
Vaccine Adjuvants ◽  
New Class ◽  
Highly Effective

scholarly journals Identification of Novel Mast Cell Activators Using Cell-Based High-Throughput Screening

2019 ◽  
Vol 24 (6) ◽  
pp. 628-640
Author(s):  
Hae Woong Choi ◽  
Cliburn Chan ◽  
Ivo D. Shterev ◽  
Heather E. Lynch ◽  
Taylor J. Robinette ◽  
...  
Keyword(s):  
Mast Cell ◽  
High Throughput ◽  
High Throughput Screening ◽  
De Novo ◽  
Effective Vaccine ◽  
Data Sets ◽  
Vaccine Adjuvants ◽  
Control Rules ◽  
Human And Mouse

Mast cells (MCs) are known to regulate innate and adaptive immunity. MC activators have recently been described as safe and effective vaccine adjuvants. Many currently known MC activators are inadequate for in vivo applications, however, and research on identifying novel MC activators is limited. In this study, we identified novel MC activators by using high-throughput screening (HTS) assays using approximately 55,000 small molecules. Data sets obtained by the primary HTS assays were statistically evaluated using quality control rules and the B-score calculation, and compounds with B-scores of >3.0 were chosen as mast cell activators (hits). These hits were re-evaluated with secondary and tertiary HTS assays, followed by further statistical analysis. From these hits, we selected 15 compounds that caused degranulation in murine and human MCs, with potential for flexible chemical modification for further study. Among these 15 compounds, ST101036, ST029248, and ST026567 exhibited higher degranulation potency than other hit compounds in both human and mouse MCs. In addition, the 15 compounds identified promote de novo synthesis of cytokines and induce the release of eicosanoids from human and mouse MCs. HTS enabled us to identify small-molecule MC activators with unique properties that may be useful as vaccine adjuvants.

scholarly journals Magic Peptide: Unique Properties of the LRR11 Peptide in the Activation of Leukotriene Synthesis in Human Neutrophils

2021 ◽  
Vol 22 (5) ◽  
pp. 2671
Author(s):  
Galina M. Viryasova ◽  
Ekaterina A. Golenkina ◽  
Tibor Hianik ◽  
Nataliya V. Soshnikova ◽  
Nina G. Dolinnaya ◽  
...  
Keyword(s):  
Defense Mechanisms ◽  
Specific Binding ◽  
Acoustic Method ◽  
Effective Vaccine ◽  
Human Neutrophils ◽  
Shear Mode ◽  
Vaccine Adjuvants ◽  
High Biological Activity ◽  
Pathogen Elimination ◽  
Cpg Odns

Neutrophil-mediated innate host defense mechanisms include pathogen elimination through bacterial phagocytosis, which activates the 5-lipoxygenase (5-LOX) product synthesis. Here, we studied the effect of synthetic oligodeoxyribonucleotides (ODNs), which mimic the receptor-recognized sites of bacterial (CpG-ODNs) and genomic (G-rich ODNs) DNAs released from the inflammatory area, on the neutrophil functions after cell stimulation with Salmonella typhimurium. A possible mechanism for ODN recognition by Toll-like receptor 9 (TLR9) and RAGE receptor has been proposed. We found for the first time that the combination of the magic peptide LRR11 from the leucine-rich repeat (LRR) of TLR9 with the CpG-ODNs modulates the uptake and signaling from ODNs, in particular, dramatically stimulates 5-LOX pathway. Using thickness shear mode acoustic method, we confirmed the specific binding of CpG-ODNs, but not G-rich ODN, to LRR11. The RAGE receptor has been shown to play an important role in promoting ODN uptake. Thus, FPS-ZM1, a high-affinity RAGE inhibitor, suppresses the synthesis of 5-LOX products and reduces the uptake of ODNs by neutrophils; the inhibitor effect being abolished by the addition of LRR11. The results obtained revealed that the studied peptide-ODN complexes possess high biological activity and can be promising for the development of effective vaccine adjuvants and antimicrobial therapeutics.

scholarly journals Inactivation of SARS-CoV-2 on surfaces and in solution with Virusend (TX-10), a novel disinfectant

2021 ◽  
Vol 3 (4) ◽  
Author(s):  
Enyia R. Anderson ◽  
Grant L. Hughes ◽  
Edward I. Patterson
Keyword(s):  
Control Measures ◽  
Effective Vaccine ◽  
Viral Titre ◽  
Indirect Contact ◽  
Highly Effective ◽  
Contact Transmission ◽  
Microbial Agents

Until an effective vaccine against SARS-CoV-2 is available on a widespread scale, the control of the COVID-19 pandemic is reliant upon effective pandemic control measures. The ability of SARS-CoV-2 to remain viable on surfaces and in aerosols, means indirect contact transmission can occur and there is an opportunity to reduce transmission using effective disinfectants in public and communal spaces. Virusend (TX-10), a novel disinfectant, has been developed as a highly effective disinfectant against a range of microbial agents. Here we investigate the ability of Virusend to inactivate SARS-CoV-2. Using surface and solution inactivation assays, we show that Virusend is able to reduce SARS-CoV-2 viral titre by 4 log10 p.f.u. ml−1 within 1 min of contact. Ensuring disinfectants are highly effective against SARS-CoV-2 is important in eliminating environmental sources of the virus to control the COVID-19 pandemic.

scholarly journals The Evolutionary History of the Chymase Locus -a Locus Encoding Several of the Major Hematopoietic Serine Proteases

2021 ◽  
Vol 22 (20) ◽  
pp. 10975
Author(s):  
Srinivas Akula ◽  
Zhirong Fu ◽  
Sara Wernersson ◽  
Lars Hellman
Keyword(s):  
Mast Cell ◽  
T Cell ◽  
Serine Proteases ◽  
Phylogenetic Trees ◽  
Granzyme B ◽  
Large Family ◽  
Cathepsin G ◽  
Immune Functions ◽  
New Class ◽  
History Of

Several hematopoietic cells of the immune system store large amounts of proteases in cytoplasmic granules. The absolute majority of these proteases belong to the large family of chymotrypsin-related serine proteases. The chymase locus is one of four loci encoding these granule-associated serine proteases in mammals. The chymase locus encodes only four genes in primates, (1) the gene for a mast-cell-specific chymotryptic enzyme, the chymase; (2) a T-cell-expressed asp-ase, granzyme B; (3) a neutrophil-expressed chymotryptic enzyme, cathepsin G; and (4) a T-cell-expressed chymotryptic enzyme named granzyme H. Interestingly, this locus has experienced a number of quite dramatic expansions during mammalian evolution. This is illustrated by the very large number of functional protease genes found in the chymase locus of mice (15 genes) and rats (18 genes). A separate expansion has also occurred in ruminants, where we find a new class of protease genes, the duodenases, which are expressed in the intestinal region. In contrast, the opossum has only two functional genes in this locus, the mast cell (MC) chymase and granzyme B. This low number of genes may be the result of an inversion, which may have hindered unequal crossing over, a mechanism which may have been a major factor in the expansion within the rodent lineage. The chymase locus can be traced back to early tetrapods as genes that cluster with the mammalian genes in phylogenetic trees can be found in frogs, alligators and turtles, but appear to have been lost in birds. We here present the collected data concerning the evolution of this rapidly evolving locus, and how these changes in gene numbers and specificities may have affected the immune functions in the various tetrapod species.

Strategies to Stimulate Innate Immunity for Designing Effective Vaccine Adjuvants

Vaccinology ◽  
2012 ◽  
pp. 13-28
Author(s):  
Heather L. Wilson ◽  
Scott Napper ◽  
George K. Mutwiri ◽  
Sylvia van Drunen Littel-van den Hurk ◽  
Hugh Townsend ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Effective Vaccine ◽  
Vaccine Adjuvants

Soybean Bowman–Birk Protease Inhibitor Is a Highly Effective Inhibitor of Human Mast Cell Chymase

1997 ◽  
Vol 344 (1) ◽  
pp. 133-138 ◽  
Author(s):  
Jeffrey H. Ware ◽  
X.Steven Wan ◽  
Harvey Rubin ◽  
Norman M. Schechter ◽  
Ann R. Kennedy
Keyword(s):  
Mast Cell ◽  
Protease Inhibitor ◽  
Human Mast Cell ◽  
Effective Inhibitor ◽  
Highly Effective ◽  
Mast Cell Chymase

Modelling the population-level impact of vaccination on the transmission of human papillomavirus type 16 in Australia

Sexual Health ◽  
2007 ◽  
Vol 4 (3) ◽  
pp. 147 ◽  
Author(s):  
David G. Regan ◽  
David J. Philp ◽  
Jane S. Hocking ◽  
Matthew G. Law
Keyword(s):  
Human Papillomavirus ◽  
Cost Effectiveness ◽  
Hpv Infection ◽  
Conclusive Evidence ◽  
Effective Vaccine ◽  
High Coverage ◽  
Hpv 16 ◽  
Highly Effective ◽  
Catch Up ◽  
The Impact

Background: Vaccines are now available to prevent the development of cervical cancer from genital human papillomavirus (HPV) infection. The decision to vaccinate depends on a vaccine’s cost-effectiveness. A rigorous cost-effectiveness model for vaccinated individuals is presented in a companion paper; this paper investigates the additional benefits the community might receive from herd immunity. Methods: A mathematical model was developed to estimate the impact of a prophylactic vaccine on transmission of HPV type 16 in Australia. The model was used to estimate the expected reduction in HPV incidence and prevalence as a result of vaccination, the time required to achieve these reductions, and the coverage required for elimination. The modelled population was stratified according to age, gender, level of sexual activity and HPV infection status using a differential equation formulation. Clinical trials show that the vaccine is highly effective at preventing persistent infection and pre-cancerous lesions. These trials do not, however, provide conclusive evidence that infection is prevented altogether. The possible modes of vaccine action were investigated to see how vaccination might change the conclusions. Results: The model predicts that vaccination of 80% of 12-year-old girls will eventually reduce HPV 16 prevalence by 60–100% in vaccinated and 7–31% in unvaccinated females. If 80% of boys are also vaccinated, reductions will be 74–100% in vaccinated and 86–96% in unvaccinated females. A campaign covering only 12-year-old girls would require 5–7 years to achieve 50% of the eventual reduction. With a catch-up campaign covering 13–26-year-olds, this delay would be reduced to only 2 years. Unrealistically high coverage in both sexes would be required to eliminate HPV 16 from the population. Under pessimistic assumptions about the duration of vaccine-conferred immunity, HPV 16 incidence is predicted to rise in some older age groups. Conclusions: Mass vaccination with a highly effective vaccine against HPV 16 has the potential to substantially reduce the incidence and prevalence of infection. Catch-up vaccination offers the potential to substantially reduce the delay before the benefits of vaccination are observed. A booster vaccination might be required to prevent an increase in incidence of infection in women over 25 years of age.

scholarly journals Exposure to Mycobacteria Primes the Immune System for Evolutionarily Diverse Heat Shock Proteins

2005 ◽  
Vol 73 (11) ◽  
pp. 7687-7696 ◽  
Author(s):  
Khaleda Rahman Qazi ◽  
Mousumi Rahman Qazi ◽  
Esther Julián ◽  
Mahavir Singh ◽  
Manuchehr Abedi-Valugerdi ◽  
...  
Keyword(s):  
Immune System ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Chlamydia Pneumoniae ◽  
Effective Vaccine ◽  
Interferon Production ◽  
Vaccine Adjuvants ◽  
Mycobacterium Vaccae ◽  
Shock Proteins ◽  
High Degree

ABSTRACT During stress conditions, such as infection, the synthesis of heat shock proteins (HSPs) in microorganisms is upregulated. Since a high degree of homology exists within each HSP family, we postulated that exposure to microorganisms could prime the immune system for evolutionarily diverse HSPs. We tested this hypothesis by priming mice with three microorganisms, namely, Mycobacterium bovis BCG, Mycobacterium vaccae, and Chlamydia pneumoniae. After this, mice received a dose of the various HSPs. We found that BCG and M. vaccae but not C. pneumoniae primed the immune system for the induction of secondary immunoglobulin G (IgG) responses to most of the HSPs tested. Analysis of the IgG1 and IgG2a profile and gamma interferon production induced against the HSPs revealed the induction of a mixture of responses. We also observed that sera from mice treated with M. vaccae and HSP70 were cross-reactive, but no antibody complexes were observed in their kidneys, which frequently are targets for autoantibody reactions. Our findings add further support for the use of HSPs as effective vaccine adjuvants.

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