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Double-Mutant Live Attenuated Brucella Vaccines

技术优势

Safety ΓÇô residual in vivo virulence of the vaccine is very lowHighly stable ΓÇô not subject to varying morphology, exhibiting increase virulence or losing immunogenicityEnhance immunogenicity ΓÇô more protective than current vaccinesDecreased potential for false positives ΓÇô easy to distinguish vaccinated hosts from those naturally infectedAttenuated strain may be applicable to humans

技术应用

A double -mutant brucellosis vaccine for cattle and humans which has two virulence genes attenuated to enable minimal infection and a marker gene to enable identification of the vaccine from wild type pathogen. This vaccine is more effective and more attenuated than current vaccines.

详细技术说明

Researchers at Montana State University previously developed two vaccines for the most common brucella bacteria - B. melitensis and B. abortus. Further work on these vaccines has lead to a single dose of B. melitensis vaccine which confers complete protection against nasal challenge. Introduction of a second mutation in the B. abortus strain resulted in a greatly attenuated strain in primary human macrophages yet remains a highly effective vaccine. This strain conferred equal protection against pulmonary B. melitensis challenge. Given the highly similar genetic homology across brucella, it is believed that the above work can be applied to the other brucella homologs.

*Abstract

Brucella is a group of 10 highly homogeneous bacteria many of which cause brucellosis ΓÇô the most common worldwide zoonotic disease. Brucellosis causes animals to abort and lowers both weight and milk production. Brucellosis in humans causes septicemia, fevers, anemia, myalgia and arthralgia - all of which can persist for years. Three primary brucella bacteria account for most instances of brucellosis. While brucellosis is relatively well controlled in domestic herd animals, outbreaks occur due to the prevalence of the disease in wild animals and its ability to cross infect domestic animals. Incidents of brucellosis in herd animals cost producers between $1.50 and $11.50 per head in testing services. Additional costs include lost livestock sales (both in the outbreak year and subsequent years). The State of Wyoming has calculated a first year cost of $200 per head alone. There are brucellosis vaccines on the market, although none approved for humans. The primary vaccine of choice, RB-51 for cattle shows only partial effectiveness at full dose and is ineffective at low doses. RB-51 also causes brucellosis in humans which complicates handling of the vaccine. Finally, RB-51 is resistant to rifampin, one of the drugs used to treat the disease post-infection. Live vaccine Rev-1 is available for goat and sheep but likewise it is virulent to humans and cannot be given to pregnant or lactating animals.

*Principal Investigation

Name: David Pascual, Professor, Ph.D.

Department: Immunology and Infectious Disease

国家/地区

美国