Abstract:Brucellosis is an important neglected zoonotic disease, and the pathogens responsible are Brucellae. In order to evaluate the immunogenicity and protective efficacy of a DNA vaccine encoding Brucella BvrR, the recombinant plasmid pCDNA-BvrR was constructed by inserting the BvrR gene fragment into a pCDNA3.0 vector. The His 6-tagged BvrR was purified with His-trap FF crude affinity chromatography and verified with an anti-histidine monoclonal antibody by western blot analysis. The specific immunoglobulin antige… Show more
“…A limitation in this study is the selection of hypovirulent strain B. abortus S19 as challenge strain for protection experiments [ 43 , 71 , 72 ]. B. abortus S19 was originally isolated as a virulent strain from a Jersey cow in 1923 and was found to become attenuated after being kept in the laboratory at room temperature for more than a year [ 41 , 42 ].…”
Brucella spp. are Gram-negative, facultative intracellular bacteria that cause brucellosis in humans and various animals. The threat of brucellosis has increased, yet currently available live attenuated vaccines still have drawbacks. Therefore, subunit vaccines, produced using protein antigens and having the advantage of being safe, cost-effective and efficacious, are urgently needed. In this study, we used core proteome analysis and a compositive RV methodology to screen potential broad-spectrum antigens against 213 pathogenic strains of Brucella spp. with worldwide geographic distribution. Candidate proteins were scored according to six biological features: subcellular localization, antigen similarity, antigenicity, mature epitope density, virulence, and adhesion probability. In the RV analysis, a total 32 candidate antigens were picked out. Of these, three proteins were selected for assessment of immunogenicity and preliminary protection in a mouse model: outer membrane protein Omp19 (used as a positive control), type IV secretion system (T4SS) protein VirB8, and type I secretion system (T1SS) protein HlyD. These three antigens with a high degree of conservation could induce specific humoral and cellular immune responses. Omp19, VirB8 and HlyD could substantially reduce the organ bacterial load of B. abortus S19 in mice and provide varying degrees of protection. In this study, we demonstrated the effectiveness of this unique strategy for the screening of potential broad-spectrum antigens against Brucella. Further evaluation is needed to identify the levels of protection conferred by the vaccine antigens against wild-type pathogenic Brucella species challenge.
“…A limitation in this study is the selection of hypovirulent strain B. abortus S19 as challenge strain for protection experiments [ 43 , 71 , 72 ]. B. abortus S19 was originally isolated as a virulent strain from a Jersey cow in 1923 and was found to become attenuated after being kept in the laboratory at room temperature for more than a year [ 41 , 42 ].…”
Brucella spp. are Gram-negative, facultative intracellular bacteria that cause brucellosis in humans and various animals. The threat of brucellosis has increased, yet currently available live attenuated vaccines still have drawbacks. Therefore, subunit vaccines, produced using protein antigens and having the advantage of being safe, cost-effective and efficacious, are urgently needed. In this study, we used core proteome analysis and a compositive RV methodology to screen potential broad-spectrum antigens against 213 pathogenic strains of Brucella spp. with worldwide geographic distribution. Candidate proteins were scored according to six biological features: subcellular localization, antigen similarity, antigenicity, mature epitope density, virulence, and adhesion probability. In the RV analysis, a total 32 candidate antigens were picked out. Of these, three proteins were selected for assessment of immunogenicity and preliminary protection in a mouse model: outer membrane protein Omp19 (used as a positive control), type IV secretion system (T4SS) protein VirB8, and type I secretion system (T1SS) protein HlyD. These three antigens with a high degree of conservation could induce specific humoral and cellular immune responses. Omp19, VirB8 and HlyD could substantially reduce the organ bacterial load of B. abortus S19 in mice and provide varying degrees of protection. In this study, we demonstrated the effectiveness of this unique strategy for the screening of potential broad-spectrum antigens against Brucella. Further evaluation is needed to identify the levels of protection conferred by the vaccine antigens against wild-type pathogenic Brucella species challenge.
“…DNA-based vaccines contain gene sequences of pathogens, which are essential for intracellular survival of Brucella spp. The immunogenicity and efficacy of these virulence genes used in DNA vaccines have been demonstrated in animal studies, including the two-component BvrR/BvrS system ( 119 ), Cu-Zn superoxide dismutase (SOD) ( 126 , 140 ), ribosomal L7/L12 or Brucella lumazine synthase (BLS) ( 139 , 141 ), B. melitensis omp31 and omp25 genes ( 125 , 142 ), antigenic surface protein (BCSP31) gene ( 120 ), SP41 ( 143 ), and ribosomal protein L9 (rL9) ( 122 ). According to the studies that have been done, DNA vaccines may have the ability to resolve the disadvantages of other brucellosis vaccines ( 119 , 120 , 144 ).…”
Section: Dna Vaccinesmentioning
confidence: 99%
“…The immunogenicity and efficacy of these virulence genes used in DNA vaccines have been demonstrated in animal studies, including the two-component BvrR/BvrS system ( 119 ), Cu-Zn superoxide dismutase (SOD) ( 126 , 140 ), ribosomal L7/L12 or Brucella lumazine synthase (BLS) ( 139 , 141 ), B. melitensis omp31 and omp25 genes ( 125 , 142 ), antigenic surface protein (BCSP31) gene ( 120 ), SP41 ( 143 ), and ribosomal protein L9 (rL9) ( 122 ). According to the studies that have been done, DNA vaccines may have the ability to resolve the disadvantages of other brucellosis vaccines ( 119 , 120 , 144 ). In most studies, animals vaccinated with different types of DNA vaccines have shown full protection against virulent strains (e.g., B. abortus S19, B. abortus 2308, B. melitensis 16M , and B. melitensis Rev1 ) ( 120 , 143 ).…”
Brucellosis is a bacterial zoonosis caused by Brucella spp. which can lead to heavy economic losses and severe human diseases. Thus, controlling brucellosis is very important. Due to humans easily gaining brucellosis from animals, animal brucellosis control programs can help the eradication of human brucellosis. There are two popular vaccines against animal brucellosis. Live attenuated Brucella abortus strain 19 (S19 vaccine) is the first effective and most extensively used vaccine for the prevention of brucellosis in cattle. Live attenuated Brucella melitensis strain Rev.1 (Rev.1 vaccine) is the most effective vaccine against caprine and ovine brucellosis. Although these two vaccines provide good immunity for animals against brucellosis, the expense of persistent serological responses is one of the main problems of both vaccines. The advantages and limitations of Brucella vaccines, especially new vaccine candidates, have been less studied. In addition, there is an urgent need for new strategies to control and eradicate this disease. Therefore, this narrative review aims to present an updated overview of the available different types of brucellosis vaccines.
“…In animal models it has been observed that T4SS is necessary for the onset of the infection (102). Recently it has been published that BvrR is a good candidate for a DNA vaccine in the murine brucellosis model, but many studies are missing (103).…”
Section: Antigenic Components Of Brucella As Virulence Factorsmentioning
Brucellosis is one of the most prevalent bacterial zoonosis of worldwide distribution. The disease is caused by
Brucella
spp., facultative intracellular pathogens. Brucellosis in animals results in abortion of fetuses, while in humans, it frequently manifests flu-like symptoms and a typical undulant fever, being osteoarthritis a common complication of the chronic infection. The two most common ways to acquire the infection in humans are through the ingestion of contaminated dairy products or by inhalation of contaminated aerosols.
Brucella
spp. enter the body mainly through the gastrointestinal and respiratory mucosa; however, most studies of immune response to
Brucella
spp. are performed analyzing models of systemic immunity. It is necessary to better understand the mucosal immune response induced by
Brucella
infection since this is the main entry site for the bacterium. In this review, some virulence factors and the mechanisms needed for pathogen invasion and persistence are discussed. Furthermore, some aspects of local immune responses induced during
Brucella
infection will be reviewed. With this knowledge, better vaccines can be designed focused on inducing protective mucosal immune response.
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