scholarly journals A Recombinant Flagellin-Poxvirus Fusion Protein Vaccine Elicits Complement-Dependent Protection Against Respiratory Challenge with Vaccinia Virus in Mice

2010 ◽  
Vol 23 (2) ◽  
pp. 201-210 ◽  
Author(s):  
Kristen N. Delaney ◽  
James P. Phipps ◽  
John B. Johnson ◽  
Steven B. Mizel
2008 ◽  
Vol 16 (1) ◽  
pp. 21-28 ◽  
Author(s):  
Steven B. Mizel ◽  
Aaron H. Graff ◽  
Nammalwar Sriranganathan ◽  
Sean Ervin ◽  
Cynthia J. Lees ◽  
...  

ABSTRACT A number of studies have clearly demonstrated that flagellin is a potent adjuvant that promotes robust immune responses when it is given with a protein antigen. In view of the potential biological and practical benefits of a recombinant protein vaccine composed of a single fusion protein containing flagellin and antigen, we have evaluated the efficacy of a fusion protein composed of flagellin and two protective antigens of Yersinia pestis (F1 and V) in eliciting protection against respiratory challenge with Y. pestis. Flagellin-F1-V was produced and purified in high yield under good manufacturing practices conditions. The fusion protein retains full Toll-like receptor 5-stimulating activity in vitro. Using a prime-boost immunization protocol, we found that flagellin-F1-V elicits robust antigen-specific humoral immunity in mice and two species of nonhuman primates. Immune mice were fully protected against intranasal challenge with 150 mean tolerated doses of Y. pestis CO92. In immune mice, the bacteria were completely cleared within 3 days after challenge. Flagellin-F1-V exhibited full stability for at least 297 days at 4°C and at least 168 days at 25°C. At between 29 and 84 days at 37°C, the protein exhibited a loss of biological activity that appeared to be associated with a substantial change in protein diameter, possibly due to oligomerization. On the basis of our results, we believe that flagellin-F1-V is an outstanding candidate for evaluation in studies with humans.


2011 ◽  
Vol 44 (13) ◽  
pp. S46
Author(s):  
Elham Mohit ◽  
Azam Bolhassani ◽  
Farnaz Zahedifard ◽  
Mohammad Taghikhani ◽  
Eslamifar Ali ◽  
...  

1988 ◽  
Vol 85 (4) ◽  
pp. 1252-1256 ◽  
Author(s):  
R. Drillien ◽  
D. Spehner ◽  
A. Kirn ◽  
P. Giraudon ◽  
R. Buckland ◽  
...  

2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Qiaohong Meng ◽  
Wenfeng Wang ◽  
Xiaowen Shi ◽  
Yongfeng Jin ◽  
Yaozhou Zhang

In animals, oral administration of the cholera toxin B (CTB) subunit conjugated to the autoantigen insulin enhances the specific immune-unresponsive state. This is called oral tolerance and is capable of suppressing autoimmune type 1 diabetes (T1D). However, the process by which the CTB-insulin (CTB-INS) protein works as a therapy for T1Din vivoremains unclear. Here, we successfully expressed a green fluorescent protein- (GFP-) tagged CTB-Ins (CTB-Ins-GFP) fusion protein in silkworms in a pentameric form that retained the native ability to activate the mechanism. Oral administration of the CTB-Ins-GFP protein induced special tolerance, delayed the development of diabetic symptoms, and suppressed T1D onset in nonobese diabetic (NOD) mice. Moreover, it increased the numbers of CD4+CD25+Foxp3+T regulatory (Treg) cells in peripheral lymph tissues and affected the biological activity of spleen cells. This study demonstrated that the CTB-Ins-GFP protein produced in silkworms acted as an oral protein vaccine, inducing immunological tolerance involving CD4+CD25+Foxp3+Treg cells in treating T1D.


2013 ◽  
Vol 58 (4) ◽  
Author(s):  
Gandhirajan Anugraha ◽  
Parasurama Jeyaprita ◽  
Jayaprakasam Madhumathi ◽  
Tamilvanan Sheeba ◽  
Perumal Kaliraj

AbstractAlthough multiple vaccine strategy for lymphatic filariasis has provided tremendous hope, the choice of antigens used in combination has determined its success in the previous studies. Multiple antigens comprising key vaccine candidates from different life cycle stages would provide a promising strategy if the antigenic combination is chosen by careful screening. In order to analyze one such combination, we have used a chimeric construct carrying the well studied B. malayi antigens thioredoxin (BmTRX) and venom allergen homologue (BmVAH) as a fusion protein (TV) and evaluated its immune responses in mice model. The efficacy of fusion protein vaccine was explored in comparison with the single antigen vaccines and their cocktail. In mice, TV induced significantly high antibody titer of 1,28,000 compared to cocktail vaccine TRX+VAH (50,000) and single antigen vaccine TRX (16,000) or VAH (50,000). Furthermore, TV elicited higher level of cellular proliferative response together with elevated levels of IFN-γ, IL-4 and IL-5 indicating a Th1/Th2 balanced response. The isotype antibody profile showed significantly high level of IgG1 and IgG2b confirming the balanced response elicited by TV. Immunization with TV antigen induced high levels of both humoral and cellular immune responses compared to either cocktail or antigen given alone. The result suggests that TV is highly immunogenic in mice and hence the combination needs to be evaluated for its prophylactic potential.


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