Targeted expression of anthrax protective antigen byLactobacillus gasserias an anthrax vaccine

2010 ◽  
Vol 5 (8) ◽  
pp. 1289-1296 ◽  
Author(s):  
Mansour Mohamadzadeh ◽  
Evelyn Durmaz ◽  
Mojgan Zadeh ◽  
Krishna Chaitanya Pakanati ◽  
Matthew Gramarossa ◽  
...  
2018 ◽  
Vol 2 (2) ◽  
pp. 51-60

Anthrax is a serious infectious disease with high mortality. The epidemiological security depends on the vaccination of susceptible animals and population at risk. But many of the existing anthrax vaccine strains possess low levels of protective antigen production and high reactogenicity. One of the most promising trends in production of new generation of vaccines is the cloning of particular determinants of immunogenicity of anthrax microbe for the creation of highly effective producers of Bacillus anthracis protective antigen. The aim of the article is to present the results of the study on the construction of recombinant Bacillus subtilis strain, producing B.anthracis protective antigen, promising for use in chemical anthrax vaccines technology. The pHT43PA plasmid containing the gene pag, providing the synthesis of protective antigen of the anthrax microbe and functioning stably in the cells of the recombinant strain Amy21(pHT43РА) of B. subtilis, was constructed on the basis of the shuttle vector pHT43. It is found out during the research, that the microbial cells of the recombinant strain Amy21(pHT43РА) of B. subtilis provide the production of immunologically active protective antigen in quantities, not inferior than anthrax vaccine strains. These data, as well as safety and simplicity of В. subtilis make it possible to continue the research of this recombinant strain as a producer of anthrax protective antigen, promising for use in vaccines production


Virology ◽  
2006 ◽  
Vol 353 (2) ◽  
pp. 344-356 ◽  
Author(s):  
Mary Ellen Smith ◽  
Martin Koser ◽  
Sa Xiao ◽  
Catherine Siler ◽  
James P. McGettigan ◽  
...  

Vaccine ◽  
2013 ◽  
Vol 31 (44) ◽  
pp. 5009-5014 ◽  
Author(s):  
Phillip R. Pittman ◽  
Diana Fisher ◽  
Xiaofei Quinn ◽  
Trevor Schmader ◽  
Julio G. Barrera-Oro

2008 ◽  
Vol 76 (10) ◽  
pp. 4538-4545 ◽  
Author(s):  
William W. Kwok ◽  
Junbao Yang ◽  
Eddie James ◽  
John Bui ◽  
Laurie Huston ◽  
...  

ABSTRACT Cellular immune responses against protective antigen (PA) of Bacillus anthracis in subjects that received the anthrax vaccine adsorbed (AVA) vaccine were examined. Multiple CD4+ T-cell epitopes within PA were identified by using tetramer-guided epitope mapping. PA-reactive CD4+ T cells with a CD45RA− phenotype were also detected by direct ex vivo staining of peripheral blood mononuclear cells (PBMC) with PA-specific tetramers. Surprisingly, PA-specific T cells were also detected in PBMC of nonvaccinees after a single cycle of in vitro PA stimulation. However, PA-reactive CD4+ T cells in nonvaccinees occurred at lower frequencies than those in vaccinees. The majority of PA-reactive T cells from nonvaccinees were CD45RA+ and exhibited a Th0/Th1 cytokine profile. In contrast, phenotyping and cytokine profile analyses of PA-reactive CD4+ T cells from vaccinees indicated that vaccination leads to commitment of PA-reactive T cells to a Th2 lineage, including generation of PA-specific, pre-Th2 central memory T cells. These results demonstrate that the current AVA vaccine is effective in skewing the development of PA CD4+ T cells to the Th2 lineage. The data also demonstrated the feasibility of using class II tetramers to analyze CD4+ cell responses and lineage development after vaccination.


2005 ◽  
Vol 73 (9) ◽  
pp. 5685-5696 ◽  
Author(s):  
Indira T. Kudva ◽  
Robert W. Griffin ◽  
Jeonifer M. Garren ◽  
Stephen B. Calderwood ◽  
Manohar John

ABSTRACTWe identified spore targets of Anthrax Vaccine Adsorbed (AVA)-induced immunity in humans by screening recombinant clones of a previously generated, limited genomicBacillus anthracisSterne (pXO1+, pXO2−) expression library of putative spore surface (spore-associated [SA]) proteins with pooled sera from human adults immunized with AVA (immune sera), the anthrax vaccine currently approved for use by humans in the United States. We identified 69 clones that reacted specifically with pooled immune sera but not with pooled sera obtained from the same individuals prior to immunization. Positive clones expressed proteins previously identified as localized on the anthrax spore surface, proteins highly expressed during spore germination, orthologs of proteins of diverse pathogens under investigation as drug targets, and orthologs of proteins contributing to the virulence of both gram-positive and gram-negative pathogens. Among the reactive clones identified by this immunological screen was one expressing a 15.2-kDa hypothetical protein encoded by a gene with no significant homology to sequences contained in databases. Further studies are required to define the subset of SA proteins identified in this study that contribute to the virulence of this pathogen. We hypothesize that optimal delivery of a subset of SA proteins identified by such studies to the immune system in combination with protective antigen (PA), the principal immunogen in AVA, might facilitate the development of defined, nonreactogenic, more-efficacious PA-based anthrax vaccines. Future studies might also facilitate the identification of SA proteins with potential to serve as targets for drug design, spore inactivation, or spore detection strategies.


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