Immunization of mice with gamma-irradiated Brucella neotomae and its recombinant strains induces protection against virulent B. abortus, B. melitensis, and B. suis challenge

Moustafa, Dina A.; Garg, Virendra Kumar; Jain, Neeta; Sriranganathan, Nammalwar; Vemulapalli, Ramesh

doi:10.1016/j.vaccine.2010.11.018

Cited by 21 publications

(18 citation statements)

References 50 publications

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“…Mice vaccinated with RB51leu B /SOD/WboA were significantly better protected than those that were vaccinated with either strain RB51leuB/SOD or RB51leu B /SOD/L7/L12 [27]. It was also recently found that non-pathogenic B. neotomae strain 5K33 can be used to overexpress homologous Brucella proteins [35]. Recombinant B. neotomae strains overexpressing SOD and/or BP26 were found to induce protection against challenge with virulent B. abortus 2308, B. melitensis 16 M, and B. suis 1330 [35].…”

Section: Resultsmentioning

confidence: 99%

“…It was also recently found that non-pathogenic B. neotomae strain 5K33 can be used to overexpress homologous Brucella proteins [35]. Recombinant B. neotomae strains overexpressing SOD and/or BP26 were found to induce protection against challenge with virulent B. abortus 2308, B. melitensis 16 M, and B. suis 1330 [35]. However, the approach of overexpression of protective antigen does not guarantee enhanced protection.…”

Section: Resultsmentioning

confidence: 99%

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Meta-analysis of variables affecting mouse protection efficacy of whole organism Brucella vaccines and vaccine candidates

et al. 2013

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BackgroundVaccine protection investigation includes three processes: vaccination, pathogen challenge, and vaccine protection efficacy assessment. Many variables can affect the results of vaccine protection. Brucella, a genus of facultative intracellular bacteria, is the etiologic agent of brucellosis in humans and multiple animal species. Extensive research has been conducted in developing effective live attenuated Brucella vaccines. We hypothesized that some variables play a more important role than others in determining vaccine protective efficacy. Using Brucella vaccines and vaccine candidates as study models, this hypothesis was tested by meta-analysis of Brucella vaccine studies reported in the literature.ResultsNineteen variables related to vaccine-induced protection of mice against infection with virulent brucellae were selected based on modeling investigation of the vaccine protection processes. The variable "vaccine protection efficacy" was set as a dependent variable while the other eighteen were set as independent variables. Discrete or continuous values were collected from papers for each variable of each data set. In total, 401 experimental groups were manually annotated from 74 peer-reviewed publications containing mouse protection data for live attenuated Brucella vaccines or vaccine candidates. Our ANOVA analysis indicated that nine variables contributed significantly (P-value < 0.05) to Brucella vaccine protection efficacy: vaccine strain, vaccination host (mouse) strain, vaccination dose, vaccination route, challenge pathogen strain, challenge route, challenge-killing interval, colony forming units (CFUs) in mouse spleen, and CFU reduction compared to control group. The other 10 variables (e.g., mouse age, vaccination-challenge interval, and challenge dose) were not found to be statistically significant (P-value > 0.05). The protection level of RB51 was sacrificed when the values of several variables (e.g., vaccination route, vaccine viability, and challenge pathogen strain) change. It is suggestive that it is difficult to protect against aerosol challenge. Somewhat counter-intuitively, our results indicate that intraperitoneal and subcutaneous vaccinations are much more effective to protect against aerosol Brucella challenge than intranasal vaccination.ConclusionsLiterature meta-analysis identified variables that significantly contribute to Brucella vaccine protection efficacy. The results obtained provide critical information for rational vaccine study design. Literature meta-analysis is generic and can be applied to analyze variables critical for vaccine protection against other infectious diseases.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Meta-analysis of variables affecting mouse protection efficacy of whole organism Brucella vaccines and vaccine candidates

et al. 2013

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“…The metabolic activity was assayed by Alamar Blue (BioSource International, Camarillo, CA), which incorporated a colorimetric growth indicator based on the detection of metabolic activity 41 42 . Briefly, the irradiated or heat incubated samples were firstly washed in normal saline (NS.)…”

Section: Methodsmentioning

confidence: 99%

X-ray Irradiated Vaccine Confers protection against Pneumonia caused by Pseudomonas Aeruginosa

Wang

Liu

et al. 2016

Sci Rep

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Pseudomonas aeruginosa is a gram-negative bacterium and one of the leading causes of nosocomial infection worldwide, however, no effective vaccine is currently available in the market. Here, we demonstrate that inactivation of the bacteria by X-ray irradiation inhibits its replication capability but retained antigenic expression functionally thus allowing its use as a potential vaccine. Mice immunized by this vaccine were challenged by the parental strain, the O-antigen-homologous strain PAO-1 (O2/O5) and heterologous strain PAO-6 (O6) in an acute pneumonia model. We further measured the protective effect of the vaccine, as well as host innate and cellular immunity responses. We found immunized mice could protect against both strains. Notably, the antiserum only had significant protective role against similar bacteria, while adoptive transfer of lymphocytes significantly controlled the spread of the virulent heterologous serogroup PAO-6 infection, and the protective role could be reversed by CD4 rather than CD8 antibody. We further revealed that vaccinated mice could rapidly recruit neutrophils to the airways early after intranasal challenge by PAO-6, and the irradiated vaccine was proved to be protective by the generated CD4+ IL-17+ Th17 cells. In conclusion, the generation of inactivated but metabolically active microbes is a promising strategy for safely vaccinating against Pseudomonas aeruginosa.

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“…In general, cell‐mediated immune responses are required to control intracellular pathogens. However, it has been shown that both arms of the immune system, Th1 and Th2, work together to provide protection against B. melitensis challenge (Delpino et al ., ; Moustafa et al ., ). The levels of total IgG were significantly higher in the mice vaccinated with OMVs + P85 compared to mice receiving only OMVs (Fig.…”

Section: Resultsmentioning

confidence: 97%

Pluronic P85 enhances the efficacy of outer membrane vesicles as a subunit vaccine againstBrucella melitensischallenge in mice

Jain-Gupta

Contreras-Rodríguez

Vemulapalli

et al. 2012

FEMS Immunol Med Microbiol

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Brucellosis is the most common zoonotic disease worldwide and there is no vaccine for human use. Brucella melitensis Rev1, a live attenuated strain, is the commercial vaccine for small ruminants to prevent B. melitensis infections but has been associated with abortions in animals. Moreover, strain Rev1 is known to cause disease in humans and cannot be used for human vaccination. Outer membrane vesicles (OMVs) obtained from B. melitensis have been shown to provide protection similar to strain Rev1 in mice against B. melitensis challenge. In the present work we tested the efficacy of Pluronic P85 as an adjuvant to enhance the efficacy of Brucella OMVs as a vaccine. P85 enhanced the in vitro secretion of TNF-α by macrophages induced with OMVs and P85. Further, P85 enhanced the protection provided by OMVs against B. melitensis challenge. This enhanced protection was associated with higher total IgG antibody production but not increased IFN-γ or IL-4 cytokine levels. Moreover, P85 alone provided significantly better clearance of B. melitensis compared to saline vaccinated mice. Further studies are warranted to find the mechanism of action of P85 that provides non-specific protection and enhances the efficacy of OMVs as a vaccine against B. melitensis.

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Immunization of mice with gamma-irradiated Brucella neotomae and its recombinant strains induces protection against virulent B. abortus, B. melitensis, and B. suis challenge

Cited by 21 publications

References 50 publications

Meta-analysis of variables affecting mouse protection efficacy of whole organism Brucella vaccines and vaccine candidates

Meta-analysis of variables affecting mouse protection efficacy of whole organism Brucella vaccines and vaccine candidates

X-ray Irradiated Vaccine Confers protection against Pneumonia caused by Pseudomonas Aeruginosa

Pluronic P85 enhances the efficacy of outer membrane vesicles as a subunit vaccine againstBrucella melitensischallenge in mice

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