Evaluation of Protection Afforded by Brucella abortus and Brucella melitensis Unmarked Deletion Mutants Exhibiting Different Rates of Clearance in BALB/c Mice

Abstract

Research for novel Brucella vaccines has focused upon the development of live vaccine strains, which have proven more efficacious than killed or subunit vaccines. In an effort to develop improved vaccines, signaturetagged mutant banks were screened to identify mutants attenuated for survival. Mutants selected from these screens exhibited various degrees of attenuation characterized by the rate of clearance, ranging from a failure to grow in macrophages after 24 h of infection to a failure to persist in the mouse model beyond 8 weeks. Ideal vaccine candidates should be safe to the host, while evoking protective immunity. In the present work, we constructed unmarked deletion mutants of three gene candidates, manBA, virB2, and asp24, in both Brucella abortus and Brucella melitensis. The ⌬asp24 mutants, which persist for extended periods in vivo, are superior to current vaccine strains and to other deletion strains tested in the mouse model against homologous challenge infection after 12, 16, and 20 weeks postvaccination. The ⌬asp24 mutants also display superior protection compared to ⌬manBA and ⌬virB2 mutants against heterologous challenge in mice. From this study, a direct association between protection against infection and cytokine response was not apparent between all vaccine groups and, therefore, correlates of protective immunity will need to be considered further. A distinct correlation between persistence of the vaccine strain and protection against infection was corroborated.

Seroprevalence and Molecular Epidemiology of Brucellosis in Cattle in Egypt

“…While, the percentages of abortion in pregnant cows suffering from brucellosis collected from individual animals were 2.29 %, 1.41 %, 2.59 % and 2.83 % for yeas 2008, 2009, 2010 and 2011 respectively. These results were lower than those reported by [28,29,30] whose recorded 16.1 %, 37.4 %, and 26 %, respectively.…”

Booster vaccination with safe, modified, live-attenuated mutants of Brucella abortus strain RB51 vaccine confers protective immunity against virulent strains of B. abortus and Brucella canis in BALB/c mice

“…To construct the plasmids for deleting cydC, cydD Table 2. Using previously published methods (Kahl-McDonagh & Ficht, 2006;, the respective plasmids pEX18DcydC, pEX18DcydD and pEX18DpurD were created by a two-round PCR amplification, restricted digestion and ligation, and then introduced into RB51 and the RB51DcydC mutant via electroporation. Transformants were selected in the presence of 100 mg carbenicillin ml 21 for the first screening and 5 % sucrose for the second screening.…”

The Burkholderia pseudomallei Δ asd Mutant Exhibits Attenuated Intracellular Infectivity and Imparts Protection against Acute Inhalation Melioidosis in Mice

“…However, we had reason to believe that the ⌬asd mutant would be more effective than previous live attenuated strains. It has been shown that a more protective immune response can be achieved by increasing short-term vaccine persistence, which we attempted with the booster vaccine (5,23,45). Unfortunately, while vaccination with the ⌬asd mutant did indeed protect against acute melioidosis, the vaccine failed to protect against chronic melioidosis.…”