Evaluation of unmarked deletion mutants as improved Brucella vaccine strains in the mouse and goat models

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dc.contributor.advisor Ficht , Thomas A . en_US
dc.contributor.committeeMember Adams , L . Garry en_US
dc.creator Kahl , Melissa Marie en_US
dc.date.accessioned 2006 -10 -30T23 :24 :43Z
dc.date.accessioned 2014 -02 -19T19 :26 :13Z
dc.date.available 2006 -10 -30T23 :24 :43Z
dc.date.available 2014 -02 -19T19 :26 :13Z
dc.date.created 2005 -08 en_US
dc.date.issued 2006 -10 -30T23 :24 :43Z
dc.identifier.uri http : / /hdl .handle .net /1969 .1 /4197
dc.description.abstract Historical data suggests that prolonged survival of Brucella vaccine organisms in the target host enhances immune protection . Recent research has focused upon the development of rough vaccine strains to avoid interference with standard diagnostic tests . Rough organisms are rapidly cleared from the host , however . In an effort to develop improved vaccine strains , we have screened signature tagged mutagenesis banks to identify mutants with varying survival characteristics . We hypothesize that in order for a vaccine to be efficacious , it must survive in the host . In order to test this , we constructed marked and unmarked deletion mutants of B . abortus and B . melitensis in genes previously demonstrated by transposon mutagenesis to attenuate in vivo and in vitro virulence . Survival and efficacy of these novel deletion mutants were then evaluated in the mouse model . The asp24 mutants , which persist for extended periods in vivo , appear superior as a vaccine candidate compared to approved vaccine strains S19 and Rev1 in the mouse model against either homologous or heterologous challenges . Once enhanced protection against infection was demonstrated in the mouse , components of immune function that appeared to be most important were identified to correlate the immune response with the observed protection . We demonstrated that the most persistent mutant , delta -asp24 , affords the greatest protection in mice against virulent challenge . In order to evaluate safety of the novel vaccine strains as well as protection against infection and abortion , we tested selected B . melitensis unmarked deletion mutants in a natural host , the goat . The delta -asp24 mutant was shown to be safe in pregnant goats while providing significant protection against infection and abortion . en_US
dc.format.extent 11457616 bytes
dc.format.medium electronic en_US
dc.format.mimetype application /pdf
dc.language.iso en _US en_US
dc.publisher Texas A &M University en_US
dc.subject Brucella en_US
dc.title Evaluation of unmarked deletion mutants as improved Brucella vaccine strains in the mouse and goat models en_US
dc.type Thesis en
dc.type.genre Electronic Dissertation en_US
dc.type.material text en_US
dc.format.digitalOrigin born digital en_US

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Evaluation of unmarked deletion mutants as improved Brucella vaccine strains in the mouse and goat models. Available electronically from http : / /hdl .handle .net /1969 .1 /4197 .

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