Are bacterial vaccine antigens T-cell epitope depleted?

Halling‐Brown, Mark; Sansom, Clare; Davies, Matthew N.; Titball, Richard W.; Moss, David S.

doi:10.1016/j.it.2008.06.001

Cited by 14 publications

(7 citation statements)

References 50 publications

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“…This is not necessarily surprising since the predicting power of those immunoinformatic strategies has not been directly compared against an empirical approach testing all ORFs (the ORFeome) of a pathogen. Moreover, at least for bacterial proteins, known protective antigens actually have less predicted epitopes than randomly selected bacterial protein sets used as a control [41].…”

Section: Discussionmentioning

confidence: 99%

Discovery of a Protective Rickettsia prowazekii Antigen Recognized by CD8+ T Cells, RP884, Using an In Vivo Screening Platform

et al. 2013

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Rickettsia prowazekii has been tested for biological warfare due to the high mortality that it produces after aerosol transmission of very low numbers of rickettsiae. Epidemic typhus, the infection caused by these obligately intracellular bacteria, continues to be a threat because it is difficult to diagnose due to initial non-specific symptoms and the lack of commercial diagnostic tests that are sensitive and specific during the initial clinical presentation. A vaccine to prevent epidemic typhus would constitute an effective deterrent to the weaponization of R. prowazekii; however, an effective and safe vaccine is not currently available. Due to the cytoplasmic niche of Rickettsia, CD8+ T-cells are critical effectors of immunity; however, the identification of antigens recognized by these cells has not been systematically addressed. To help close this gap, we designed an antigen discovery strategy that uses cell-based vaccination with antigen presenting cells expressing microbe's proteins targeted to the MHC class I presentation pathway. We report the use of this method to discover a protective T-cell rickettsial antigen, RP884, among a test subset of rickettsial proteins.

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Section: Discussionmentioning

confidence: 99%

Discovery of a Protective Rickettsia prowazekii Antigen Recognized by CD8+ T Cells, RP884, Using an In Vivo Screening Platform

et al. 2013

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“…So possession of T-cell and B-cell epitopes is in certain senses independent of sub-cellular location, and they may in principle be possessed by any protein. As we have said, there is evidence for T-cell epitope depletion in pathogenic proteins [35]; or it may be that just picking immune-accessible proteins naturally favours proteins rich in antibody and helper T-cell epitopes, as opposed to cytotoxic T-cell epitopes, at least for membrane proteins. As data accumulates on the specific responses made to differently located accessible proteins we can build these recondite subtleties into prediction strategies.…”

Section: Identifying Antigens Through Subcellular Location Predictionmentioning

confidence: 97%

Computer aided selection of candidate vaccine antigens

et al. 2010

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Immunoinformatics is an emergent branch of informatics science that long ago pullulated from the tree of knowledge that is bioinformatics. It is a discipline which applies informatic techniques to problems of the immune system. To a great extent, immunoinformatics is typified by epitope prediction methods. It has found disappointingly limited use in the design and discovery of new vaccines, which is an area where proper computational support is generally lacking. Most extant vaccines are not based around isolated epitopes but rather correspond to chemically-treated or attenuated whole pathogens or correspond to individual proteins extract from whole pathogens or correspond to complex carbohydrate. In this chapter we attempt to review what progress there has been in an as-yet-underexplored area of immunoinformatics: the computational discovery of whole protein antigens. The effective development of antigen prediction methods would significantly reduce the laboratory resource required to identify pathogenic proteins as candidate subunit vaccines. We begin our review by placing antigen prediction firmly into context, exploring the role of reverse vaccinology in the design and discovery of vaccines. We also highlight several competing yet ultimately complementary methodological approaches: sub-cellular location prediction, identifying antigens using sequence similarity, and the use of sophisticated statistical approaches for predicting the probability of antigen characteristics. We end by exploring how a systems immunomics approach to the prediction of immunogenicity would prove helpful in the prediction of antigens.

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“…There is experimental evidence that those predictions are very limiting (Wu et al, 2011). In fact, using predictive algorithms in bioinformatics approaches, known protective bacterial antigens actually have less predicted epitopes recognized by T cells than randomly selected bacterial protein sets used as a control (Halling-Brown et al, 2008). …”

Section: Modern Vaccinology Concepts Applied To Scrub Typhusmentioning

confidence: 99%

Approaches to vaccines against Orientia tsutsugamushi

Valbuena¹,

Walker²

2013

Front. Cell. Inf. Microbio.

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Scrub typhus is a severe mite-borne infection caused by Orientia tsutsugamushi, an obligately intracellular bacterium closely related to Rickettsia. The disease explains a substantial proportion of acute undifferentiated febrile cases that require hospitalization in rural areas of Asia, the North of Australia, and many islands of the Pacific Ocean. Delayed antibiotic treatment is common due to the lack of effective commercially available diagnostic tests and the lack of specificity of the early clinical presentation. The systemic infection of endothelial cells that line the vasculature with Orientia can lead to many complications and fatalities. In survivors, immunity does not last long, and is poorly cross-reactive among numerous strains. In addition, chronic infections are established in an unknown number of patients. All those characteristics justify the pursuit of a prophylactic vaccine against O. tsutsugamushi; however, despite continuous efforts to develop such a vaccine since World War II, the objective has not been attained. In this review, we discuss the history of vaccine development against Orientia to provide a clear picture of the challenges that we continue to face from the perspective of animal models and the immunological challenges posed by an intracellular bacterium that normally triggers a short-lived immune response. We finish with a proposal for development of an effective and safe vaccine for scrub typhus through a new approach with a strong focus on T cell-mediated immunity, empirical testing of the immunogenicity of proteins encoded by conserved genes, and assessment of protection in relevant animal models that truly mimic human scrub typhus.

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Are bacterial vaccine antigens T-cell epitope depleted?

Cited by 14 publications

References 50 publications

Discovery of a Protective Rickettsia prowazekii Antigen Recognized by CD8+ T Cells, RP884, Using an In Vivo Screening Platform

Discovery of a Protective Rickettsia prowazekii Antigen Recognized by CD8+ T Cells, RP884, Using an In Vivo Screening Platform

Computer aided selection of candidate vaccine antigens

Approaches to vaccines against Orientia tsutsugamushi

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