scholarly journals Multifunctional Fructose 1,6-Bisphosphate Aldolase as a Therapeutic Target

2021 ◽  
Vol 8 ◽  
Author(s):  
David B. Pirovich ◽  
Akram A. Da’dara ◽  
Patrick J. Skelly
Keyword(s):  
Pathogenic Bacteria ◽  
High Specificity ◽  
Structural Features ◽  
Amino Acid Identity ◽  
Metazoan Parasites ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
The Many ◽  
Fructose 1,6 Bisphosphate ◽  
Moonlighting Functions

Fructose 1,6-bisphosphate aldolase is a ubiquitous cytosolic enzyme that catalyzes the fourth step of glycolysis. Aldolases are classified into three groups: Class-I, Class-IA, and Class-II; all classes share similar structural features but low amino acid identity. Apart from their conserved role in carbohydrate metabolism, aldolases have been reported to perform numerous non-enzymatic functions. Here we review the myriad “moonlighting” functions of this classical enzyme, many of which are centered on its ability to bind to an array of partner proteins that impact cellular scaffolding, signaling, transcription, and motility. In addition to the cytosolic location, aldolase has been found the extracellular surface of several pathogenic bacteria, fungi, protozoans, and metazoans. In the extracellular space, the enzyme has been reported to perform virulence-enhancing moonlighting functions e.g., plasminogen binding, host cell adhesion, and immunomodulation. Aldolase’s importance has made it both a drug target and vaccine candidate. In this review, we note the several inhibitors that have been synthesized with high specificity for the aldolases of pathogens and cancer cells and have been shown to inhibit classical enzyme activity and moonlighting functions. We also review the many trials in which recombinant aldolases have been used as vaccine targets against a wide variety of pathogenic organisms including bacteria, fungi, and metazoan parasites. Most of such trials generated significant protection from challenge infection, correlated with antigen-specific cellular and humoral immune responses. We argue that refinement of aldolase antigen preparations and expansion of immunization trials should be encouraged to promote the advancement of promising, protective aldolase vaccines.

scholarly journals The Essential Role of DOCK8 in Humoral Immunity

2010 ◽  
Vol 29 (3-4) ◽  
pp. 141-150 ◽  
Author(s):  
Katrina L. Randall ◽  
Teresa Lambe ◽  
Chris C. Goodnow ◽  
Richard J. Cornall
Keyword(s):  
Essential Role ◽  
Immunological Synapse ◽  
Transplant Rejection ◽  
Inherited Disease ◽  
Adaptive Responses ◽  
Humoral Immune ◽  
Social Burden ◽  
Humoral Immune Responses ◽  
A Genome ◽  
The Many

The processes that normally generate and maintain adaptive immunity and immunological memory are poorly understood, and yet of fundamental importance when infectious diseases place such a major economic and social burden on the world's health and agriculture systems. Defects in these mechanisms also underlie the many forms of human primary immunodeficiency. Identifying these mechanisms in a systematic way is therefore important if we are to develop better strategies for treating and preventing infection, inherited disease, transplant rejection and autoimmunity. In this review we describe a genome-wide screen in mice for the genes important for generating these adaptive responses, and describe two independent DOCK8 mutant mice strains identified by this screen. DOCK 8 was found to play an essential role in humoral immune responses and to be important in the proper formation of the B cell immunological synapse.

Immune responses of mice to inactivated rabies vaccine administered orally: potentiation by Quillaja saponin

1986 ◽  
Vol 32 (5) ◽  
pp. 414-420 ◽  
Author(s):  
I. Maharaj ◽  
K. J. Froh ◽  
J. B. Campbell
Keyword(s):  
Immune Responses ◽  
Oral Vaccine ◽  
Neutralizing Antibody ◽  
Rabies Vaccine ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Antibody Titres ◽  
The Many ◽  
Antibody Levels ◽  
Quillaja Saponin

Administered orally, Quillaja saponin markedly potentiated the humoral immune responses of mice fed inactivated rabies vaccine, and significantly increased their resistance to subsequent intracerebral challenge with live rabies virus. Although mean serum neutralizing antibody titres were generally 8- to 16-fold higher when vaccine was given intraperitoneally, orally administered vaccine, with saponin, stimulated production of high protective antibody levels that were maintained for at least 6 months. The potentiating effect of saponin appeared to be mediated through several mechanisms, one of which was by increasing the permeability of the intestinal mucosa, allowing increased uptake of viral antigen. The potentiating effect was enhanced when saponin was administered in advance (up to at least 16 h) of the oral vaccine. Mice tolerated the effective saponin doses without any visible signs of distress or injury. In view of the many favourable physiological activities and low toxicity of orally delivered saponins, it is suggested that they may find more general applications in the immunopotentiation of oral vaccines.

Specific humoral immune responses in 12 cases of food sensitization to sesame seed

1997 ◽  
Vol 27 (11) ◽  
pp. 1285-1291 ◽  
Author(s):  
M. N. KOLOPP-SARDA ◽  
D. A. MONERET-VAUTRIN ◽  
B. GOBERT ◽  
G. KANNY ◽  
M. BRODSCHII ◽  
...  
Keyword(s):  
Immune Responses ◽  
Sesame Seed ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Food Sensitization

Production and immunological evaluation of epitope-based preventative pneumococcal candidate vaccine comprising immunodominant epitopes from PspA, CbpA, PhtD and PiuA antigens

2020 ◽  
Vol 22 ◽  
Author(s):  
Hesam Dorosti ◽  
Navid Nezafat ◽  
Reza Heidari ◽  
Mohammad Bagher Ghoshoon ◽  
Ahmad Gholami ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Pneumococcal Vaccine ◽  
Peptide Vaccine ◽  
Promising Alternative ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Serotype Replacement ◽  
Tnf Α ◽  
Immunological Evaluation ◽  
Immunodominant Epitopes

Background: Streptococcus pneumoniae is a leading cause of pneumonia, mostly in children less than five years and elderly people. Although the pneumoniae polysaccharide vaccine (PPV) and pneumonia conjugate vaccines (PCV) are the efficient pneumococcal vaccine in adult and children groups, but the serotype replacement of S. pneumoniae strains causes the reduction in the efficacy of PPV and PCV vaccines. Epitope-based vaccines are a promising alternative to the present capsular antigen vaccines. Methods: In this study, we evaluated cellular and humoral immune responses induced by our novel designed multi-epitope vaccine in BALB/c mice. CD8+ cytolytic T lymphocytes (CTLs) epitopes were selected from PspA and CbpA antigens, and CD4+ helper T lymphocytes (HTLs) epitopes were chosen from PhtD and PiuA antigens. PorB, the TLR2 agonist, as an adjuvant, was employed to increase the immunogenicity of the vaccine. Results and conclusion: The high levels of specific anti-peptide vaccine IgG and an increase in the level of IgG2 in the vaccinated group demonstrated our vaccine could elicit a robust antibody production. The significant increase in IFN-γ, IL-2, TNF-α, IL-4, IL-6, and decrease in IL-10 showed that, the designed vaccine could be proposed as the efficient preventative pneumococcal vaccine in the mouse model.

Prospective Application of Aptamer-based Assays and Therapeutics in Bloodstream Infections

2020 ◽  
Vol 20 (10) ◽  
pp. 831-840
Author(s):  
Weibin Li
Keyword(s):  
Pathogenic Bacteria ◽  
Genetic Diagnosis ◽  
Bloodstream Infections ◽  
High Specificity ◽  
Peptide Sequence ◽  
High Morbidity ◽  
Specificity And Sensitivity ◽  
Prospective Application ◽  
Small Molecule Therapeutics

Sepsis is still a severe health problem worldwide with high morbidity and mortality. Blood bacterial culture remains the gold standard for the detection of pathogenic bacteria in bloodstream infections, but it is time-consuming, and both the sophisticated equipment and well-trained personnel are required. Immunoassays and genetic diagnosis are expensive and limited to specificity and sensitivity. Aptamers are single-stranded deoxyribonucleic acid (ssDNA) and ribonucleic acid (RNA) oligonucleotide or peptide sequence generated in vitro based on the binding affinity of aptamer-target by a process known as Systematic Evolution of Ligands by Exponential Enrichment (SELEX). By taking several advantages over monoclonal antibodies and other conventional small-molecule therapeutics, such as high specificity and affinity, negligible batch-to-batch variation, flexible modification and production, thermal stability, low immunogenicity and lack of toxicity, aptamers are presently becoming promising novel diagnostic and therapeutic agents. This review describes the prospective application of aptamerbased laboratory diagnostic assays and therapeutics for pathogenic bacteria and toxins in bloodstream infections.

scholarly journals Humoral immune responses to AAV gene therapy in the ocular compartment

2021 ◽  
Author(s):  
Michael Whitehead ◽  
Andrew Osborne ◽  
Patrick Yu‐Wai‐Man ◽  
Keith Martin
Keyword(s):  
Gene Therapy ◽  
Immune Responses ◽  
Humoral Immune ◽  
Humoral Immune Responses
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