Design of a mimotope-peptide based double epitope vaccine against disseminated candidiasis

Xin, Hong; Glee, Pati M.; Adams, Abby; Mohiuddin, Farhan; Eberle, Karen E.

doi:10.1016/j.vaccine.2019.03.061

Cited by 11 publications

(12 citation statements)

References 43 publications

(28 reference statements)

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“…These would likely provide more effective prevention against fungal infections in the future, particularly if combined with other cell wall component epitopes, including polysaccharides or covalently bound cell wall proteins. Care should always be taken, however, to avoid using epitopes, in vaccine design, that are shared between the pathogen and the host, an issue that may be particularly important when using evolutionarily conserved enzymes from basic metabolic cycles [ 181 , 182 , 183 , 184 ].…”

Section: Confirmed Roles In Candidal Virulence and Pathogenicitymentioning

confidence: 99%

Moonlighting Proteins at the Candidal Cell Surface

et al. 2020

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The cell wall in Candida albicans is not only a tight protective envelope but also a point of contact with the human host that provides a dynamic response to the constantly changing environment in infection niches. Particularly important roles are attributed to proteins exposed at the fungal cell surface. These include proteins that are stably and covalently bound to the cell wall or cell membrane and those that are more loosely attached. Interestingly in this regard, numerous loosely attached proteins belong to the class of “moonlighting proteins” that are originally intracellular and that perform essentially different functions in addition to their primary housekeeping roles. These proteins also demonstrate unpredicted interactions with non-canonical partners at an a priori unexpected extracellular location, achieved via non-classical secretion routes. Acting both individually and collectively, the moonlighting proteins contribute to candidal virulence and pathogenicity through their involvement in mechanisms critical for successful host colonization and infection, such as the adhesion to host cells, interactions with plasma homeostatic proteolytic cascades, responses to stress conditions and molecular mimicry. The documented knowledge of the roles of these proteins in C. albicans pathogenicity has utility for assisting the design of new therapeutic, diagnostic and preventive strategies against candidiasis.

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Section: Confirmed Roles In Candidal Virulence and Pathogenicitymentioning

confidence: 99%

Moonlighting Proteins at the Candidal Cell Surface

et al. 2020

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“…Phages selected by phage library biopanning rarely display peptides that are identical in their primary sequence to a peptide of the protein antigen of interest; the method more commonly leads to the identification of mimotope peptides. A mimotope peptide can mimic both a linear epitope and a discontinuous conformational epitope [13]; it can also mimic a non-peptidic epitope, such as a lipopolysaccharide epitope or a glycan [14,15]. Genome-fragment phage display libraries are collections of phages engineered to express short polypeptides of a pathogen’s proteome.…”

Section: The Use Of Filamentous Bacteriophages For the Induction Amentioning

confidence: 99%

Arming Filamentous Bacteriophage, a Nature-Made Nanoparticle, for New Vaccine and Immunotherapeutic Strategies

et al. 2019

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The pharmaceutical use of bacteriophages as safe and inexpensive therapeutic tools is collecting renewed interest. The use of lytic phages to fight antibiotic-resistant bacterial strains is pursued in academic and industrial projects and is the object of several clinical trials. On the other hand, filamentous bacteriophages used for the phage display technology can also have diagnostic and therapeutic applications. Filamentous bacteriophages are nature-made nanoparticles useful for their size, the capability to enter blood vessels, and the capacity of high-density antigen expression. In the last decades, our laboratory focused its efforts in the study of antigen delivery strategies based on the filamentous bacteriophage ‘fd’, able to trigger all arms of the immune response, with particular emphasis on the ability of the MHC class I restricted antigenic determinants displayed on phages to induce strong and protective cytotoxic responses. We showed that fd bacteriophages, engineered to target mouse dendritic cells (DCs), activate innate and adaptive responses without the need of exogenous adjuvants, and more recently, we described the display of immunologically active lipids. In this review, we will provide an overview of the reported applications of the bacteriophage carriers and describe the advantages of exploiting this technology for delivery strategies.

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“…In later work ( Xin et al, 2019 ), the MAP was conjugated to synthetic mimotope peptides used to replace the β-(Man) 3 glycan moiety. This was undertaken to eliminate the need for oligosaccharide synthesis, thus simplifying vaccine production.…”

Section: Aldolase As a Vaccine Targetmentioning

confidence: 99%

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

Pirovich

Da’dara

Skelly

2021

Front. Mol. Biosci.

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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.

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Design of a mimotope-peptide based double epitope vaccine against disseminated candidiasis

Cited by 11 publications

References 43 publications

Moonlighting Proteins at the Candidal Cell Surface

Moonlighting Proteins at the Candidal Cell Surface

Arming Filamentous Bacteriophage, a Nature-Made Nanoparticle, for New Vaccine and Immunotherapeutic Strategies

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

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