Abstract
Brucellosis is a bacterial zoonotic disease affecting several mammalian species that is transmitted to humans by direct or indirect contact with infected animals or their products. In cattle, brucellosis is almost invariably caused by Brucella abortus. Live, attenuated Brucella vaccines are commonly used to prevent illness in cattle, but can cause abortions in pregnant animals. It is, therefore, desirable to design an effective and safer vaccine against Brucella. We have used specific Brucella antigens that induce immunity and protection against B. abortus. A novel recombinant multi-epitope DNA vaccine specific for brucellosis was developed. To design the vaccine construct, we employed bioinformatics tools to predict epitopes present in Cu–Zn superoxide dismutase and in the open reading frames of the genomic island-3 (BAB1_0260, BAB1_0270, BAB1_0273, and BAB1_0278) of Brucella. We successfully designed a multi-epitope DNA plasmid vaccine chimera that encodes and expresses 21 epitopes. This DNA vaccine induced a specific humoral and cellular immune response in BALB/c mice. It induced a typical T-helper 1 response, eliciting production of immunoglobulin G2a and IFN-γ particularly associated with the Th1 cell subset of CD4+ T cells. The production of IL-4, an indicator of Th2 activation, was not detected in splenocytes. Therefore, it is reasonable to suggest that the vaccine induced a predominantly Th1 response. The vaccine induced a statistically significant level of protection in BALB/c mice when challenged with B. abortus 2308. This is the first use of an in silico strategy to a design a multi-epitope DNA vaccine against B. abortus.
Highlights
Brucellosis, caused by facultative Gram-negative intracellular coccobacilli grouped in the genus Brucella [1], is a zoonotic disease with a high incidence and prevalence worldwide
The results showed that pV-MEB DNA vaccine confers protection against B. abortus 2308
The availability of bioinformatics tools and databases allow the design of vaccines without the need for in vitro manipulation of a pathogenic microorganism
Summary
Brucellosis, caused by facultative Gram-negative intracellular coccobacilli grouped in the genus Brucella [1], is a zoonotic disease with a high incidence and prevalence worldwide. The most frequent clinical symptom in livestock after Brucella infection is abortion [2]. The disease has a wide spectrum of clinical manifestations. Brucellosis can impose a significant economic burden on animal production (reduction in milk production, abortions, delayed in conception). It has been estimated that more than 300,000 animals, out of the 1.4 billion in the world, are infected [4]. Brucellosis is one of the most common zoonotic diseases in humans, with more than 500,000 cases reported annually. Depending upon the system of controls and the socioeconomic conditions, official reports only account for a fraction of the true incidence of this disease, and different countries have reported from 0.09 to 1603 cases per million inhabitants [5]
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