The Brucella melitensis M5-90ΔmanB live vaccine candidate is safer than M5-90 and confers protection against wild-type challenge in BALB/c mice

2017 ◽  
Vol 112 ◽  
pp. 148-155 ◽  
Author(s):  
Junbo Zhang ◽  
Shuanghong Yin ◽  
Dewu Yi ◽  
Hong Zhang ◽  
Zhiqiang Li ◽  
...  
Keyword(s):  
Vaccine Candidate ◽  
Brucella Melitensis ◽  
Live Vaccine ◽  
Wild Type

An Effective Live Vaccine Strain Of Trypanosoma Cruzi Prevents Chagas Disease In The Mouse Model

2020 ◽  
Author(s):  
Bijay Jha ◽  
Sanjay Varikuti ◽  
Nicholas Bishop ◽  
Gregory dos Santos ◽  
Jacquelyn McDonald ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Vaccine Candidate ◽  
Etiologic Agent ◽  
Live Vaccine ◽  
Parasite Line ◽  
Wild Type ◽  
Knock Out ◽  
Cell Responses ◽  
Deficient Mice

Abstract Trypanosoma cruzi is the etiologic agent of Chagas disease for which there are no prophylactic vaccines. Cyclophilin 19 is a secreted cis-trans peptidyl isomerase expressed in all life stages of Trypanosoma cruzi, which in the insect stage leads to the inactivation of insect anti-parasitic peptides and parasite transformation and in intracellular amastigotes participates in generating ROS enhancing parasite growth. We have generated a parasite knock-out mutant of Cyp19 which fails to replicate in cell culture or in mice indicating that lack of Cyp19 is critical for infectivity. Knock-out parasites fail to replicate in or cause clinical disease in immune-deficient mice further validating their lack of virulence. Repeated inoculation of knock-out parasites into immuno-competent mice elicits parasite-specific antibodies and T-cell responses. Challenge of immunized mice with wild-type parasites is 100% effective at preventing disease. These results indicate that the knock-out parasite line is a live vaccine candidate for Chagas disease.

Improvement of the attenuated mutant strain of Brucella melitensis Rev1 as a potential vaccine candidate

Biologia ◽  
2021 ◽  
Author(s):  
Elham Mehdizadeh Marzenaki ◽  
Ali Reza Saeedinia ◽  
Mehdi Zeinoddini ◽  
Ali Asghar Deldar
Keyword(s):  
Mutant Strain ◽  
Vaccine Candidate ◽  
Brucella Melitensis ◽  
Potential Vaccine Candidate ◽  
Potential Vaccine

scholarly journals Construction of Brucella melitensis ghost as a putative vaccine candidate against re-emerging disease – Brucellosis

2020 ◽  
Vol 101 ◽  
pp. 475-476
Author(s):  
B. Sumathi ◽  
B. Veeregowda ◽  
S. Byregowda ◽  
D. Rathnamma ◽  
S. Rajeswari ◽  
...  
Keyword(s):  
Vaccine Candidate ◽  
Brucella Melitensis ◽  
Emerging Disease

scholarly journals Deletion of znuA Virulence Factor Attenuates Brucella abortus and Confers Protection against Wild-Type Challenge

2006 ◽  
Vol 74 (7) ◽  
pp. 3874-3879 ◽  
Author(s):  
Xinghong Yang ◽  
Todd Becker ◽  
Nancy Walters ◽  
David W. Pascual
Keyword(s):  
Brucella Abortus ◽  
Deletion Mutant ◽  
Pasteurella Multocida ◽  
Brucella Melitensis ◽  
Normal Growth ◽  
Wild Type ◽  
Minimal Growth ◽  
M Genome ◽  
S19 Vaccine ◽  
Knockout Mutation

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.

scholarly journals Intranasal Interleukin-12 Treatment for Protection against Respiratory Infection with the Francisella tularensis Live Vaccine Strain

2005 ◽  
Vol 73 (4) ◽  
pp. 2306-2311 ◽  
Author(s):  
Nathalie S. Duckett ◽  
Sofia Olmos ◽  
Douglas M. Durrant ◽  
Dennis W. Metzger
Keyword(s):  
Respiratory Infection ◽  
Francisella Tularensis ◽  
Vaccine Strain ◽  
Live Vaccine ◽  
Interleukin 12 ◽  
Live Vaccine Strain ◽  
Wild Type ◽  
Intranasal Infection ◽  
Ifn Γ

ABSTRACT Francisella tularensis is a gram-negative intracellular bacterium that can induce lethal respiratory infection in humans and rodents. However, little is known about the role of innate or adaptive immunity in protection from respiratory tularemia. In the present study, the role of interleukin-12 (IL-12) in inducing protective immunity in the lungs against intranasal infection of mice with the live vaccine strain (LVS) of F. tularensis was investigated. It was found that gamma interferon (IFN-γ) and IL-12 were strictly required for protection, since mice deficient in IFN-γ, IL-12 p35, or IL-12 p40 all succumbed to LVS doses that were sublethal for wild-type mice. Furthermore, exogenous IL-12 treatment 24 h before intranasal infection with a lethal dose of LVS (10,000 CFU) significantly decreased bacterial loads in the lungs, livers, and spleens of wild-type BALB/c and C57BL/6 mice and allowed the animals to survive infection; such protection was not observed in IFN-γ-deficient mice. The resistance induced by IL-12 to LVS infection was still observed in NK cell-deficient beige mice but not in CD8−/− mice. These results demonstrate that exogenous IL-12 delivered intranasally can prevent respiratory tularemia through a mechanism that is at least partially dependent upon the expression of IFN-γ and CD8 T cells.

Construction and characterization of a replication-competent human adenovirus type 3-based vector as a live-vaccine candidate and a viral delivery vector

Vaccine ◽  
2009 ◽  
Vol 27 (8) ◽  
pp. 1145-1153 ◽  
Author(s):  
Qiwei Zhang ◽  
Xiaobo Su ◽  
Donald Seto ◽  
Bo-jian Zheng ◽  
Xingui Tian ◽  
...  
Keyword(s):  
Vaccine Candidate ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Live Vaccine ◽  
Delivery Vector ◽  
Type 3

scholarly journals Evaluation of Replication and Cross-Reactive Antibody Responses of H2 Subtype Influenza Viruses in Mice and Ferrets

2010 ◽  
Vol 84 (15) ◽  
pp. 7695-7702 ◽  
Author(s):  
Grace L. Chen ◽  
Elaine W. Lamirande ◽  
Chin-Fen Yang ◽  
Hong Jin ◽  
George Kemble ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Pandemic Influenza ◽  
Vaccine Candidate ◽  
Influenza Virus Vaccine ◽  
Influenza Viruses ◽  
Antibody Responses ◽  
Wild Type ◽  
Preparedness Planning ◽  
Kinetics Of ◽  
Reactive Antibody

ABSTRACT H2 influenza viruses have not circulated in humans since 1968, and therefore a large segment of the population would likely be susceptible to infection should H2 influenza viruses reemerge. The development of an H2 pandemic influenza virus vaccine candidate should therefore be considered a priority in pandemic influenza preparedness planning. We selected a group of geographically and temporally diverse wild-type H2 influenza viruses and evaluated the kinetics of replication and compared the ability of these viruses to induce a broadly cross-reactive antibody response in mice and ferrets. In both mice and ferrets, A/Japan/305/1957 (H2N2), A/mallard/NY/1978 (H2N2), and A/swine/MO/2006 (H2N3) elicited the broadest cross-reactive antibody responses against heterologous H2 influenza viruses as measured by hemagglutination inhibition and microneutralization assays. These data suggested that these three viruses may be suitable candidates for development as live attenuated H2 pandemic influenza virus vaccines.

scholarly journals The Riemerella anatipestiferAS87_01735Gene Encodes Nicotinamidase PncA, an Important Virulence Factor

2016 ◽  
Vol 82 (19) ◽  
pp. 5815-5823 ◽  
Author(s):  
Xiaolan Wang ◽  
Beibei Liu ◽  
Yafeng Dou ◽  
Hongjie Fan ◽  
Shaohui Wang ◽  
...  
Keyword(s):  
Type Strain ◽  
Wild Type Strain ◽  
Vaccine Candidate ◽  
Wild Type ◽  
Salvage Pathway ◽  
Effective Protection ◽  
Domestic Ducks ◽  
Content Type ◽  
Key Enzyme ◽  
Important Virulence Factor

ABSTRACTRiemerella anatipestiferis a major bacterial pathogen that causes septicemic and exudative diseases in domestic ducks. In our previous study, we found that deletion of theAS87_01735gene significantly decreased the bacterial virulence ofR. anatipestiferstrain Yb2 (mutant RA625). TheAS87_01735gene was predicted to encode a nicotinamidase (PncA), a key enzyme that catalyzes the conversion of nicotinamide to nicotinic acid, which is an important reaction in the NAD+salvage pathway. In this study, theAS87_01735gene was expressed and identified as the PncA-encoding gene, using an enzymatic assay. Western blot analysis demonstrated thatR. anatipestiferPncA was localized to the cytoplasm. The mutant strain RA625 (named Yb2ΔpncAin this study) showed a similar growth rate but decreased NAD+quantities in both the exponential and stationary phases in tryptic soy broth culture, compared with the wild-type strain Yb2. In addition, Yb2ΔpncA-infected ducks showed much lower bacterial loads in their blood, and no visible histological changes were observed in the heart, liver, and spleen. Furthermore, Yb2ΔpncAimmunization of ducks conferred effective protection against challenge with the virulent wild-type strain Yb2. Our results suggest that theR. anatipestiferAS87_01735gene encodes PncA, which is an important virulence factor, and that the Yb2ΔpncAmutant can be used as a novel live vaccine candidate.IMPORTANCERiemerella anatipestiferis reported worldwide as a cause of septicemic and exudative diseases of domestic ducks. ThepncAgene encodes a nicotinamidase (PncA), a key enzyme that catalyzes the conversion of nicotinamide to nicotinic acid, which is an important reaction in the NAD+salvage pathway. In this study, we identified and characterized thepncA-homologous geneAS87_01735inR. anatipestiferstrain Yb2.R. anatipestiferPncA is a cytoplasmic protein that possesses similar PncA activity, compared with other organisms. Generation of thepncAmutant Yb2ΔpncAled to a decrease in the NAD+content, which was associated with decreased capacity for invasion and attenuated virulence in ducks. Furthermore, Yb2ΔpncAimmunization of ducks conferred effective protection against challenge with the virulent wild-type strain Yb2. Altogether, these results suggest that PncA contributes to the virulence ofR. anatipestiferand that the Yb2ΔpncAmutant can be used as a novel live vaccine candidate.

scholarly journals Protective Immunity to Pseudomonas aeruginosa Induced with a Capsid-Modified Adenovirus Expressing P. aeruginosa OprF

2007 ◽  
Vol 81 (24) ◽  
pp. 13801-13808 ◽  
Author(s):  
Stefan Worgall ◽  
Anja Krause ◽  
JianPing Qiu ◽  
Ju Joh ◽  
Neil R. Hackett ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Protective Immunity ◽  
Vaccine Candidate ◽  
Wild Type ◽  
Cell Responses ◽  
Rgd Sequence ◽  
Hexon Protein ◽  
Repeat Administration ◽  
Antigen Presenting ◽  
Fiber Gene

ABSTRACT This study focuses on the development of a new clinical vaccine candidate (AdOprF.RGD.Epi8) against Pseudomonas aeruginosa using an E1− E3− adenovirus (Ad) vector expressing OprF (AdOprF.RGD.Epi8) and modifications of the Ad genome providing two capsid changes: (i) modification of the Ad hexon gene to incorporate an immune-dominant OprF epitope (Epi8) into loop 1 of the hexon, enabling repeat administration to boost the anti-OprF immune response, and (ii) modification of the fiber gene to incorporate an integrin-binding RGD sequence to enhance gene delivery to antigen-presenting cells. Western analysis confirmed that AdOprF.RGD.Epi8 expresses OprF, contains Epi8 in the hexon protein, and enhances gene transfer to dendritic cells compared to AdOprF, a comparable Ad vector expressing OprF with an unmodified capsid. Intramuscular immunization of C57BL/6 mice with AdOprF.RGD.Epi8 resulted in the generation of anti-OprF antibodies at comparable levels to those induced following immunization with AdOprF, but immunization with AdOprF.RGD.Epi8 was associated with increased CD4 and CD8 gamma interferon T-cell responses against OprF as well as increased survival against lethal pulmonary challenge with agar-encapsulated P. aeruginosa. Importantly, repeat administration of AdOprF.RGD.Epi8 resulted in boosting of the humoral anti-OprF response as well as increased protection, whereas no boosting could be achieved with repeat administration of AdOprF. This suggests that the capsid-modified AdOprF.RGD.Epi8 vector is a more effective immunogen compared to a comparable wild-type Ad capsid, making it a good candidate for an anti-P. aeruginosa vaccine.

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