Glyceradehyde-3-phosphate dehydrogenase as a suitable vaccine candidate for protection against bacterial and parasitic diseases

doi:10.1016/j.vaccine.2015.11.072

Vaccine

Volume 34, Issue 8, 17 February 2016, Pages 1012-1017

https://doi.org/10.1016/j.vaccine.2015.11.072 Get rights and content

Highlights

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GAPDH proteins from several species are surface-exposed and bind to extracellular matrices.
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We present evidence of the success of GAPDH proteins in vaccine trials for protection against numerous pathogens.
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Before considering using GAPDH as a vaccine component, the possibility of antibody cross-reaction with the GAPDH of the host must be considered.

Abstract

The enzyme glyceraldehyde-3-P-dehydrogenase (GAPDH) has been identified as having other properties in addition to its key role in glycolysis. The ability of GAPDH to bind to numerous extracellular matrices, modulation of host-immune responses, a role in virulence and surface location has prompted numerous investigators to postulate that GAPDH may be a good vaccine candidate for protection against numerous pathogens. Although immune responses against GAPDH have been described for many microorganisms, vaccines containing GAPDH have been successfully tested in few cases including those against the trematode—Schistosoma mansoni, the helminth—Enchinococcus multilocularis; the nematode filaria— Litomosoides sigmodontis; fish pathogens such as Aeromonas spp., Vibrio spp., Edwarsiella spp., and Streptococcus iniae; and environmental streptococci, namely, Streptococcus uberis and Streptococcus dysgalactiae. Before GAPDH-based vaccines are considered viable options for protection against numerous pathogens, we need to take into account the homology between the host and pathogen GAPDH proteins to prevent potential autoimmune reactions, thus protective GAPDH epitopes unique to the pathogen protein must be identified.

Introduction

Glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12) is a key glycolytic enzyme that reversibly catalyzes the transformation of glyceraldehyde-3-phosphate to 1-3 di-phosphoglycerate. A vast range of publications describes the numerous functions of the eukaryotic form of GAPDH. Amongst the different properties attributed to this protein are involvements in DNA repair, control of gene expression, membrane trafficking, cell signalling, interaction with RNA and other proteins particularly in neurodegenerative diseases [1], [2], [3]. Recent work also suggests that GAPDH possesses various roles other than its function in glycolysis amongst which are attachment to other proteins, modification of intracellular signalling, and evasion from immune surveillance of the host, and ultimately a role in microbial virulence. Because of these recently discovered properties of GAPDH, several investigators have proposed that GAPDH may be a suitable target for a vaccine to control diseases caused by numerous pathogens. The use of GAPDH as a vaccine component is the focus of this review article.

Section snippets

Surface localization and binding to matrix proteins

The GAPDH protein, like many housekeeping proteins, has been presumed to exist only in the cytoplasm of both prokaryotic and eukaryotic cells. It was not until 1985 that eukaryotic GAPDH was first localized on the cell membranes of haematopoietic cells [4]. This protein was confirmed to be homologous to GAPDH by peptide mapping and molecular cloning [4]. Two years later, a report described the isolation of a gene encoding an immunogenic 37 kDa protein highly homologous to human GAPDH that could

GAPDH as a vaccine target

The fact that GAPDH in many species was located on the cell surface, binds to matrix proteins, has a putative role in virulence prompted the question whether it could be used as a target for vaccines against several pathogens. The list of pathogens and outcomes of vaccination/challenge trials are summarized in Table 1.

Conclusions

Based on the current evidence, it appears that GAPDH would be a good candidate for a human vaccine against S. mansoni [46], E. multilocularis [47] and human filariasis [49] although more research needs to be done in this area. The high degree of conservation of GAPDH within most species suggests that a vaccine based on GAPDH protein from one microorganism could protect against other unrelated pathogens. This is the case for several fish pathogens like Aeromonas, Edwarsiella and Vibrio species

Acknowledgements

Our research was supported by The National Sciences and Engineering Research Council of Canada (NSERC); the former Canadian Bacterial Diseases Network (CBDN); Dairy Farmers of Canada, Dairy Farmers of Ontario, Alberta Milk Producers; British Columbia Innovation Agriculture Fund; Saskatchewan Agriculture Development Fund (ADF); Canadian Bovine Mastitis Research Network (Now Canadian Bovine Mastitis and Milk Quality Research Network); The Alberta Agriculture Research Institute (AARI); The Beef