Abstract
Brucellosis is diagnosed by detection of antibodies in the blood of animals and humans that are specific for two carbohydrate antigens, termed A and M, which are present concurrently in a single cell wall O-polysaccharide. Animal brucellosis vaccines contain these antigenic determinants, and consequently infected and vaccinated animals cannot be differentiated as both groups produce A and M specific antibodies. We hypothesized that chemical synthesis of a pure A vaccine would offer unique identification of infected animals by a synthetic M diagnostic antigen that would not react with antibodies generated by this vaccine. Two forms of the A antigen, a hexasaccharide and a heptasaccharide conjugated to tetanus toxoid via reducing and nonreducing terminal sugars, were synthesized and used as lead vaccine candidates. Mouse antibody profiles to these immunogens showed that to avoid reaction with diagnostic M antigen it was essential to maximize the induction of anti-A antibodies that bind internal oligosaccharide sequences and minimize production of antibodies directed toward the terminal nonreducing monosaccharide. This objective was achieved by conjugation of Brucella O-polysaccharide to tetanus toxoid via its periodate oxidized terminal nonreducing monosaccharide, thereby destroying terminal epitopes and focusing the antibody response on internal A epitopes. This establishes the method to resolve the decades-long challenge of how to create effective brucellosis vaccines without compromising diagnosis of infected animals.
Highlights
Investing in the development of new tools needed to effectively control these diseases, in the field of diagnostics
It is against this background that World Health Organization (WHO) and the DFID Animal Health Programme decided to set up a joint meeting focusing not on emerging zoonoses, but on zoonoses which are ‘endemic’ in the sense that, they are subject to occasional epidemics, they are found throughout the developing world where the conditions for their maintenance and spread exist
Additional components of rabies disease burden include (a) the side-effects of nerve-tissue vaccines which are still used widely in parts of Asia and contribute 0.04 million disability-adjusted life years (DALYs) to the disease burden, (b) economic losses, which amount to US$ 583 million annually, largely due to the direct and indirect costs of human post-exposure vaccination, (c) the fear and anxiety associated with receiving a bite from a suspected rabid dog, which could account for as many as 165 000 DALYs not included in the total above, (d) an animal welfare burden as a consequence of public attitude and treatment of animals in areas where dog rabies is endemic and (e) the extinction threat posed by dog rabies to several endangered wildlife populations
Summary
Measures to safeguard human health and to control disease in livestock and other animals for the prevention of the transmission of animal-borne or zoonotic diseases are too often undertaken in isolation of one another. There is widespread recognition that a cluster of ‘neglected’ diseases exists, which above all affect poor marginalised populations and which neither attract the health resources nor the research needed to control them effectively These diseases play a key role in perpetuating poverty. The endemic zoonoses occupy a unique position at the interface between zoonotic disease, neglected diseases and poverty perpetuated by poor health and threats to livelihoods It is against this background that WHO and the DFID Animal Health Programme decided to set up a joint meeting focusing not on emerging zoonoses, but on zoonoses which are ‘endemic’ in the sense that, they are subject to occasional epidemics, they are found throughout the developing world where the conditions for their maintenance and spread exist. Because they affect livestock, causing lowered productivity or death, they attack people’s health, and their livelihoods
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