Modulation of immune responses in Balb/c mice vaccinated with Brucella abortus CuZn superoxide dismutase synthetic peptide vaccine

Tabatabai, Louisa B.; Pugh, George

doi:10.1016/0264-410x(94)90035-3

Cited by 86 publications

(71 citation statements)

References 24 publications

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“…Similarly, B. abortus SOD (BaSOD) deletion mutants were found to be susceptible to O 2 ·Ϫ -mediated killing in vitro and by macrophages in mice (46) and exhibited decreased survival during the initial phases of infection (47). Furthermore, our work found that immunization with a synthetic peptide derived from BaSOD was immunoprotective in mice (48). Supporting and extending these previous results, we now show that neutralization of NmSOD with a monoclonal antibody (49) also protected mice during infection.…”

supporting

confidence: 87%

Structural, Functional, and Immunogenic Insights on Cu,Zn Superoxide Dismutase Pathogenic Virulence Factors from Neisseria meningitidis and Brucella abortus

et al. 2015

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Bacterial pathogens Neisseria meningitidis and Brucella abortus pose threats to human and animal health worldwide, causing meningococcal disease and brucellosis, respectively. Mortality from acute N. meningitidis infections remains high despite antibiotics, and brucellosis presents alimentary and health consequences. Superoxide dismutases are master regulators of reactive oxygen and general pathogenicity factors and are therefore therapeutic targets. Cu,Zn superoxide dismutases (SODs) localized to the periplasm promote survival by detoxifying superoxide radicals generated by major host antimicrobial immune responses. We discovered that passive immunization with an antibody directed at N. meningitidis SOD (NmSOD) was protective in a mouse infection model. To define the relevant atomic details and solution assembly states of this important virulence factor, we report high-resolution and X-ray scattering analyses of NmSOD and of SOD from B. abortus (BaSOD). The NmSOD structures revealed an auxiliary tetrahedral Cu-binding site bridging the dimer interface; mutational analyses suggested that this metal site contributes to protein stability, with implications for bacterial defense mechanisms. Biochemical and structural analyses informed us about electrostatic substrate guidance, dimer assembly, and an exposed C-terminal epitope in the NmSOD dimer. In contrast, the monomeric BaSOD structure provided insights for extending immunogenic peptide epitopes derived from the protein. These collective results reveal unique contributions of SOD to pathogenic virulence, refine predictive motifs for distinguishing SOD classes, and suggest general targets for antibacterial immune responses. The identified functional contributions, motifs, and targets distinguishing bacterial and eukaryotic SOD assemblies presented here provide a foundation for efforts to develop SOD-specific inhibitors of or vaccines against these harmful pathogens. IMPORTANCEBy protecting microbes against reactive oxygen insults, SODs aid survival of many bacteria within their hosts. Despite the ubiquity and conservation of these key enzymes, notable species-specific differences relevant to pathogenesis remain undefined. To probe mechanisms that govern the functioning of Neisseria meningitidis and Brucella abortus SODs, we used X-ray structures, enzymology, modeling, and murine infection experiments. We identified virulence determinants common to the two homologs, assembly differences, and a unique metal reservoir within meningococcal SOD that stabilizes the enzyme and may provide a safeguard against copper toxicity. The insights reported here provide a rationale and a basis for SOD-specific drug design and an extension of immunogen design to target two important pathogens that continue to pose global health threats.

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confidence: 87%

Structural, Functional, and Immunogenic Insights on Cu,Zn Superoxide Dismutase Pathogenic Virulence Factors from Neisseria meningitidis and Brucella abortus

et al. 2015

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“…The improvement to the methods of cloning and purifying proteins has led to the use of purified recombinant proteins as cellular vaccines in experimental trials. These preparations as well as the synthetic peptides are more convenient to use than attenuated vaccines but are not able to confer a high degree of protection or induce a strong CMI response [23]. In view of this situation, recent vaccine research has concentrated on the development of alternative vaccines, such as DNA vaccines.…”

Section: Discussionmentioning

confidence: 99%

“…Recombinant antigens of Brucella spp. such as Bacterioferritine (BFR) and the P39 [17], HtrA [18], GroEL [19,20], GroES [21], Cu-Zn superoxide dismutase (SOD) [22,23], YajC [24], L7/L12 [25], outer membrane protein 31 (Omp31) [26], ialB and omp25 [16], BLS-L7/L12 [27], BLSOmp31 [28] and lumazine synthase [29] have been shown to induce humoral and CMI responses in mice. In addition, Omp31, P39, L7/L12, BLSOmp31, lumazine synthase and peptides comprising certain epitopes of Cu-Zn SOD induced some level of protection in a mouse model of infection.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the immunogenicity and the protective efficacy in mice of a DNA vaccine encoding SP41 from Brucella melitensis

Al-Mariri

Abbady

2013

J Infect Dev Ctries

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Introduction: Brucella melitensis is a facultative intracellular Gram-negative bacterial pathogen that may enter the host via ingestion or inhalation, or through conjunctiva or skin abrasions. Some Brucella spp surface proteins (SPs) play an important role in bacterial adhesion and invasion and thus represent targets for the host immune system. Brucella spp surface protein with apparent molecular mass of 41 kDa interacts selectively with HeLa cells. Methodology: To evaluate the role of SP41 (41 kDa) as a DNA vaccine against Brucella spp., pCISP41, a plasmid construct for protein expression in mammalian cells, was established. Exogenous SP41 was detected in pCISP41-transfected Vero cell line by immune blotting using specific polyclonal antibody. The protective role of pCISP41 against B. melitensis 16M in mice was evaluated by measuring B and T cell responses in comparison to those achieved with attenuated B. melitensis Rev. 1 vaccine. Results: BALB/c mice injected with pCISP41 were able to develop SP41-specific serum immunoglobulin G (IgG) antibodies. In addition, splenocytes from DNA-SP41-vaccinated mice elicited a T-cell-proliferative response and also induced gamma interferon (IFN-γ) production, but not interleukin-5 (IL-5), suggesting the induction of a T-helper-1-dominated immune response. Vaccination with attenuated B. melitensis Rev.1 strain induced better protection levels than DNA vaccination with SP41 against B. melitensis 16M in mice. Conclusion: Such responses play an important role against intracellular infecting agents such as Brucella spp. Altogether, our data suggest that SP41 may represent a promising candidate for DNA vaccination against brucellosis, but more investigation to increase its protective efficacy should be done.

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“…A recombinant salmonella expressing a soluble B. abortus protein (BCSP-31) was tested in mice [50, 511 and swine [5 11, but no protective activity was registered. Protection was demonstrated against B. abortus by immunising mice with a peptide derived from the sequence of the B. abortus Cu-Zn superoxide-dismutase; however, the whole recombinant protein was not efficacious [52]. More recently a purified recombinant ribosomal protein was shown to be protective in mice, inducing both immune cells and antibodies [53].…”

Section: Discussionmentioning

confidence: 99%

Evaluation Of Immunogenicity and Protective Activity in Balb/C Mice of the 25-kDa Major Outer-Membrane Protein Of Brucella Melitensis (Omp25) Expressed in Escherichia Coli

Bowden

Cloeckaert²,

Zygmunt³

et al. 1998

Journal of Medical Microbiology

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The antibody response specific to the 25-kDa major outer-membrane protein (Omp25) of Brucella melitensis expressed in Escherichia coli was assessed in BALB/c mice. Groups of mice were immunised and boosted either with sonicated E. coli carrying plasmid pAC2533 -E. coli (pAC2533) -expressing the gene coding for Omp25 (omp25 gene) of B. melitensis, or with E. coli carrying plasmid pUCl9 -E. coli (pUC19). One control group received saline. The evolution of antibody responses was investigated by indirect ELISA with whole rough (R) B. melitensis H38 cells as antigen. Serum antibody titres of mice immunised with E. coli (pAC2533) were appreciably higher than those of mice immunised with E. coli (pUC19). The specificity to Omp25 of murine antibodies induced by E. coli (pAC2533) was demonstrated by SDS-PAGE and immunoblotting of five B. melitensis strains. Binding of antibody in E. coli (pAC2533) immune sera to the surface of B. melitensis strains differing in their smooth lipopolysaccharide (S-LPS) expression was also studied by whole-cell ELISA and by flow cytometry. Antibody reactivity to R and smooth-rough (S-R) was much stronger than that to smooth (S) B. melitensis strains, indicating a much better accessibility of Omp25 to antibody on strains lacking or expressing less O-polysaccharide on their surface. The antibodies to Omp25 were predominantly of IgG2a isotype. The capacity of E. coli (pAC2533) to induce protective immune responses against four challenge strains of B. melitensis was further evaluated in mice. Significant reductions in splenic infections, in comparison with mice immunised with E. coli (pUC19) and unimmunised (saline injection) mice, were observed in R B. melitensis B115, S-R B. melitensis EP and S B. melitensis H38 infected mice. Protection against S B. melitensis 16M was not significant. The data from the present study, together with previous results, suggest that humoral immunity against probably conformational, well-exposed epitopes of the Omp25 could contribute to protective mechanisms against B. melitensis infection in mice.

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Modulation of immune responses in Balb/c mice vaccinated with Brucella abortus CuZn superoxide dismutase synthetic peptide vaccine

Cited by 86 publications

References 24 publications

Structural, Functional, and Immunogenic Insights on Cu,Zn Superoxide Dismutase Pathogenic Virulence Factors from Neisseria meningitidis and Brucella abortus

Structural, Functional, and Immunogenic Insights on Cu,Zn Superoxide Dismutase Pathogenic Virulence Factors from Neisseria meningitidis and Brucella abortus

Evaluation of the immunogenicity and the protective efficacy in mice of a DNA vaccine encoding SP41 from Brucella melitensis

Evaluation Of Immunogenicity and Protective Activity in Balb/C Mice of the 25-kDa Major Outer-Membrane Protein Of Brucella Melitensis (Omp25) Expressed in Escherichia Coli

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