scholarly journals Effect of P39 Gene Deletion in LiveBrucella Vaccine Strains on Residual Virulence and Protective Activity in Mice

1998 ◽  
Vol 66 (11) ◽  
pp. 5561-5564 ◽  
Author(s):  
Anne Tibor ◽  
Isabelle Jacques ◽  
Laurence Guilloteau ◽  
Jean-Michel Verger ◽  
Maggy Grayon ◽  
...  

ABSTRACT The 39-kilodalton protein (P39) has previously been shown to be an immunodominant protein in Brucella infections. P39 gene deletion mutants of vaccine strains Brucella abortus S19 and Brucella melitensis Rev.1 were constructed by gene replacement. This deletion did not significantly modify the residual virulence of both vaccine strains in CD-1 mice. CD-1 mice vaccinated with the parent or mutant strains were protected against a virulent challenge. Mutant vaccine strains devoid of P39 could provide a means for differentiating vaccinated from infected animals.

2006 ◽  
Vol 74 (7) ◽  
pp. 4048-4057 ◽  
Author(s):  
M. M. Kahl-McDonagh ◽  
T. A. Ficht

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, signature-tagged 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 Δasp24 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 Δasp24 mutants also display superior protection compared to ΔmanBA and ΔvirB2 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.


2013 ◽  
Vol 9 (2) ◽  
pp. 653-658 ◽  
Author(s):  
XIU-RAN WANG ◽  
GUANG-MOU YAN ◽  
RUI ZHANG ◽  
XU-LONG LANG ◽  
YAN-LING YANG ◽  
...  

2021 ◽  
Vol 254 ◽  
pp. 109004
Author(s):  
Nedjma Lounes ◽  
Falk Melzer ◽  
Ashraf E. Sayour ◽  
Hassiba Tali Maamar ◽  
Kheira Rahal ◽  
...  

2006 ◽  
Vol 74 (7) ◽  
pp. 3874-3879 ◽  
Author(s):  
Xinghong Yang ◽  
Todd Becker ◽  
Nancy Walters ◽  
David W. Pascual

ABSTRACT znuA is known to be an important factor for survival and normal growth under low Zn2+ concentrations for Escherichia coli, Haemophilus spp., Neisseria gonorrhoeae, and Pasteurella multocida. We hypothesized that the znuA gene present in Brucella melitensis 16 M would be similar to znuA in B. abortus and questioned whether it may also be an important factor for growth and virulence of Brucella abortus. Using the B. melitensis 16 M genome sequence, primers were designed to construct a B. abortus deletion mutant. A znuA knockout mutation in B. abortus 2308 (ΔznuA) was constructed and found to be lethal in low-Zn2+ medium. When used to infect macrophages, ΔznuA B. abortus showed minimal growth. Further study with ΔznuA B. abortus showed that its virulence in BALB/c mice was attenuated, and most of the bacteria were cleared from the spleen within 8 weeks. Protection studies confirmed the ΔznuA mutant as a potential live vaccine, since protection against wild-type B. abortus 2308 challenge was as effective as that obtained with the RB51 or S19 vaccine strain.


2001 ◽  
Vol 69 (8) ◽  
pp. 4816-4822 ◽  
Author(s):  
Ayman Al-Mariri ◽  
Anne Tibor ◽  
Pascal Mertens ◽  
Xavier De Bolle ◽  
Patrick Michel ◽  
...  

ABSTRACT The P39 and the bacterioferrin (BFR) antigens of Brucella melitensis 16M were previously identified as T dominant antigens able to induce both delayed-type hypersensivity in sensitized guinea pigs and in vitro gamma interferon (IFN-γ) production by peripheral blood mononuclear cells from infected cattle. Here, we analyzed the potential for these antigens to function as a subunitary vaccine against Brucella abortus infection in BALB/c mice, and we characterized the humoral and cellular immune responses induced. Mice were injected with each of the recombinant proteins alone or adjuvanted with either CpG oligodeoxynucleotides (CpG ODN) or non-CpG ODN. Mice immunized with the recombinant antigens with CpG ODN were the only group demonstrating both significant IFN-γ production and T-cell proliferation in response to either Brucella extract or to the respective antigen. The same conclusion holds true for the antibody response, which was only demonstrated in mice immunized with recombinant antigens mixed with CpG ODN. The antibody titers (both immunoglobulin G1 [IgG1] and IgG2a) induced by P39 immunization were higher than the titers induced by BFR (only IgG2a). Using a B. abortus 544 challenge, the level of protection was analyzed and compared to the protection conferred by one immunization with the vaccine strain B19. Immunization with P39 and CpG ODN gave a level of protection comparable to the one conferred by B19 at 4 weeks postchallenge, and the mice were still significantly protected at 8 weeks postchallenge, although to a lesser extent than the B19-vaccinated group. Intriguingly, no protection was detected after BFR vaccination. All other groups did not demonstrate any protection.


2015 ◽  
Vol 11 (11) ◽  
pp. 3129-3136 ◽  
Author(s):  
Namal V. C. Coorey ◽  
James H. Matthews ◽  
David S. Bellows ◽  
Paul H. Atkinson

Identifying Saccharomyces cerevisiae genome-wide gene deletion mutants that confer hypersensitivity to a xenobiotic aids the elucidation of its mechanism of action (MoA).


2016 ◽  
Vol 5 (3) ◽  
Author(s):  
Francesco Casalinuovo ◽  
Lucia Ciambrone ◽  
Antonio Cacia ◽  
Paola Rippa

A study was conducted in order to evaluate the contamination by <em>Brucella</em> spp. of meat from animals slaughtered because they resulted positive for brucellosis at some time during their life, given that European legislation allows these meats to be freely marketed. After slaughter and before delivery to market outlets, swab samples were taken from 307 carcasses of infected animals: 40 cattle, 60 sheep and 207 goats. The swabs were subsequently analyzed by means of polymerase chain reaction (PCR) tests. In addition, bacteriological tests were carried out on the lymph nodes and internal organs of the same animals. <em>Brucella</em> spp. was detected by means of PCR in 25/307 carcasses (8%): 1 bovine (2.5%), 9 sheep (15%) and 15 goats (7.2%) and was isolated, by means of a cultural method, in 136/307 carcasses (44%). Moreover, additional analysis, performed on lymph nodes from the same carcasses that had proved positive by PCR allowed to highlight type 3 <em>Brucella abortus</em> in the bovine carcass and type 3 <em>Brucella melitensis</em> in the sheep and goat carcasses. The study shows that the cattle, sheep and goats meat of animals slaughtered because they have tested positive for brucellosis, may be contaminated by <em>Brucella</em> spp. As this could constitute a real risk of transmission to both butchery personnel and consumers, so the meat of animals infected by <em>Brucella</em> spp. should be analyzed before being marketed and, PCR technique performed on swabs proved more useful, practical and faster than the traditional bacteriological method.


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