Design and Synthesis of a Universal Antigen to Detect Brucellosis

Guiard, Julie; Paszkiewicz, Eugenia; Sadowska, Joanna; Bundle, David R.

doi:10.1002/ange.201302303

Cited by 5 publications

(12 citation statements)

References 29 publications

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“…Specific oligosaccharides that match the configuration of an M epitope while minimising flanking regions that would otherwise create attractive A epitopes have recently been developed (52). Such specific, discrete structures are not produced in nature.…”

Section: Insights Into Anti-brucella Immune Responsesmentioning

confidence: 99%

The quest for a true One Health perspective of brucellosis

Godfroid¹,

DeBolle²,

Roop³

et al. 2014

Rev. Sci. Tech. OIE

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SummaryOne Health is an interdisciplinary collaboration that aims at mitigating risks to human health arising from microorganisms present in non-human animal species, which have the potential to be transmitted and cause disease in humans. Different degrees of scientific collaboration and sectoral integration are needed for different types of zoonotic diseases, depending on the health and associated economic gains that can be expected from a One Health approach. Indeed, mitigating zoonotic risks related to emerging diseases with pandemic potential is different from mitigating risks related to endemic zoonotic diseases like brucellosis. Likewise, management of brucellosis at the wildlife-livestock interface in wildlife conservation areas is in essence different from mitigating transmission of a given Brucella species within its preferential host species, which in turn is different from mitigating the spillover of a given Brucella species to non-preferential host species, humans included. Brucellosis economic models often oversimplify and/or wrongly assess transmission between reservoir hosts and spillover hosts. Moreover, they may not properly value non-market outcomes, such as avoidance of human disease, consumer confidence and conservation biology issues. As a result, uncertainty is such that the economic predictions of these models can be questionable. Therefore, understanding the infection biology of Brucella species is a prerequisite. This paper reviews and highlights important features of the infection biology of Brucella species and the changing epidemiology of brucellosis that need to be integrated into a true One Health perspective of brucellosis.

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Section: Insights Into Anti-brucella Immune Responsesmentioning

confidence: 99%

The quest for a true One Health perspective of brucellosis

Godfroid¹,

DeBolle²,

Roop³

et al. 2014

Rev. Sci. Tech. OIE

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show abstract

“…For resource-poor countries, the amount of vaccine produced, and hence the reduction in cost, could be greatly enhanced by first passaging B. suis 145 through a mouse (a 5-fold increase in PS yield) and by not using TCA to remove glycoproteins (a 2-fold increase in PS yield). Alternatively, perhaps the most attractive approach would be for a pharmaceutical to produce PS synthetically (30), in bulk and without requiring containment or high security.…”

Section: Discussionmentioning

confidence: 99%

Thermostable Cross-Protective Subunit Vaccine against Brucella Species

Cherwonogrodzky

Barabé

Grigat

et al. 2014

Clin Vaccine Immunol

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A subunit vaccine candidate was produced from Brucella suis 145 (biovar 4; expressing both the A antigen of Brucella abortus and the M antigen of Brucella melitensis). The preparation consisted mostly of polysaccharide (PS; >90% [wt/wt]; both cell-associated PS and exo-PS were combined) and a small amount of protein (1 to 3%) with no apparent nucleic acids. Vaccinated mice were protected (these had a statistically significant reduction in bacterial colonization compared to that of unvaccinated controls) when challenged with representative strains of three Brucella species most pathogenic for humans, i.e., B. abortus, B. melitensis, and B. suis. As little as 1 ng of the vaccine, without added adjuvant, protected mice against B. suis 145 infection (5 ؋ 10 5 CFU), and a single injection of 1 g of this subunit vaccine protected mice from B. suis 145 challenge for at least 14 months. A single immunization induced a serum IgG response to Brucella antigens that remained elevated for up to 9 weeks. The use of heat (i.e., boiling-water bath, autoclaving) in the vaccine preparation showed that it was thermostable. This method also ensured safety and security. The vaccine produced was immunogenic and highly protective against multiple strains of Brucella and represents a promising candidate for further evaluation.

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“…Our recent studies 12 began prior to publication of the definitive clarification of the Brucella OPS structure reported by Kubler-Kielb and Vinogradov. 11 We synthesized pentasaccharide 1 in which the 1,3 linkage occurs between Rh4NFo residues 2 and 3.…”

Section: Synthesis Of Oligosaccharides Containing Brucella mentioning

confidence: 99%

“…Differentiation of infected from vaccinated animals (DIVA) is not possible with the most protective vaccines, and this limits efforts to combat the disease. Definitive structural studies of Brucella OPS 11 in combination with chemical syntheses of diagnostic antigens 12 , 13 and potential conjugate vaccines have identified an approach that facilitates DIVA. 14 , 15 These developments suggest an approach that could break a decades-old scientific impasse for mass brucellosis vaccination in animals.…”

Section: Introductionmentioning

confidence: 99%

Brucellosis: Improved Diagnostics and Vaccine Insights from Synthetic Glycans

Bundle

McGiven

2017

Acc. Chem. Res.

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ConspectusBrucellosis is a serious zoonotic bacterial disease that is ranked by the World Health Organization among the top seven “neglected zoonoses” that threaten human health and cause poverty. It is a costly, highly contagious disease that affects ruminants, cattle, sheep, goats, and other productive animals such as pigs. Symptoms include abortions, infertility, decreased milk production, weight loss, and lameness. Brucellosis is also the most common bacterial disease that is transmitted from animals to humans, with approximately 500 000 new human cases each year. Detection and slaughter of infected animals is required to eradicate the disease, as vaccination alone is currently insufficient. However, as the most protective vaccines compromise serodiagnosis, this creates policy dilemmas, and these often result in the failure of eradication and control programs. Detection of antibodies to the Brucella bacterial cell wall O-polysaccharide (OPS) component of smooth lipopolysaccharide is used in diagnosis of this disease, and the same molecule contributes important protective efficacy to currently deployed veterinary whole-cell vaccines. This has set up a long-standing paradox that while Brucella OPS confers protective efficacy to vaccines, its presence results in similar antibody profiles in infected and vaccinated animals. Consequently, differentiation of infected from vaccinated animals (DIVA) is not possible, and this limits efforts to combat the disease. Recent clarification of the chemical structure of Brucella OPS as a block copolymer of two oligosaccharide sequences has provided an opportunity to utilize unique oligosaccharides only available via chemical synthesis in serodiagnostic tests for the disease. These oligosaccharides show excellent sensitivity and specificity compared with the native polymer used in current commercial tests and have the added advantage of assisting discrimination between brucellosis and infections caused by several bacteria with OPS that share some structural features with those of Brucella. During synthesis and immunochemical evaluation of these synthetic antigens, it became apparent that an opportunity existed to create a polysaccharide–protein conjugate vaccine that would not create antibodies that give false positive results in diagnostic tests for infection. This objective was reduced to practice, and immunization of mice showed that antibodies to the Brucella A antigen could be developed without reacting in a diagnostic test based on the M antigen. A conjugate vaccine of this type could readily be developed for use in humans and animals. However, as chemical methods advance and modern methods of bacterial engineering mature, it is expected that the principles elucidated by these studies could be applied to the development of an inexpensive and cost-effective vaccine to combat endemic brucellosis in animals.

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Design and Synthesis of a Universal Antigen to Detect Brucellosis

Cited by 5 publications

References 29 publications

The quest for a true One Health perspective of brucellosis

The quest for a true One Health perspective of brucellosis

Thermostable Cross-Protective Subunit Vaccine against Brucella Species

Brucellosis: Improved Diagnostics and Vaccine Insights from Synthetic Glycans

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