Tan, W.G.* ; Zubkova, I.* ; Kachko, A.* ; Wells, F.* ; Adler, H. ; Sutter, G.* ; Major, M.E.*
     
    
        
Qualitative differences in cellular immunogenicity elicited by hepatitis C virus T-Cell vaccines employing prime-boost regimens.
    
    
        
    
    
        
        PLoS ONE 12:e0181578 (2017)
    
    
    
      
      
	
	    T-cell based vaccines have been considered as attractive candidates for prevention of hepatitis C virus (HCV) infections. In this study we compared the magnitude and phenotypic characteristics of CD8+ T-cells induced by three commonly used viral vectors, Adenovirus-5 (Ad5), Vaccinia virus (VV) and Modified Vaccinia Ankara (MVA) expressing the HCV NS3/4A protein. C57/BL6 mice were primed with DNA expressing NS3/4A and boosted with each of the viral vectors in individual groups of mice. We then tracked the vaccine-induced CD8+ T-cell responses using pentamer binding and cytokine production analysis. Overall, our data indicate that the memory cells induced by Ad5 were inferior to those induced by VV or MVA. We found that Ad5 boosting resulted in rapid expansion and significantly higher frequencies of NS3-specific T-cells compared to VV and MVA boosting. However, the functional profiles, assessed through analysis of the memory cell marker CD127 and the anti-apoptotic molecule Bcl-2 in the blood, spleen, and liver; and measurements of interferon-gamma, tumor necrosis factor-alpha, and interleukin-2 production indicated significantly lower frequencies of long-lived memory T-cells following Ad5 boosting compared to VV and MVA. This same set of analyses suggested that the memory cells induced following boosting with MVA were superior to those induced by both Ad5 and VV. This superiority of the MVA-induced CD8+ T-cells was confirmed following surrogate challenge of mice with a recombinant mouse herpes virus expressing the HCV NS3 protein. Higher levels of NS3-specific CD8+ T-cells displaying the functional markers CD69, Ki67 and Granzyme B were found in the spleens of mice boosted with MVA compared to VV and Ad5, both alone and in combination. These data suggest that MVA may be a more successful viral vector for induction of effective CD8+ T-cell responses against hepatitis C virus.
	
	
	    
	
       
      
	
	    
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        Publication type
        Article: Journal article
    
 
    
        Document type
        Scientific Article
    
 
    
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        Keywords
        Immune-responses; Viral Clearance; Infection; Chimpanzees; Hcv; Persistence; Differentiation; Restoration; Vaccination; Expression
    
 
    
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        Language
        english
    
 
    
        Publication Year
        2017
    
 
    
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        HGF-reported in Year
        2017
    
 
    
    
        ISSN (print) / ISBN
        1932-6203
    
 
    
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	    Volume: 12,  
	    Issue: 7,  
	    Pages: ,  
	    Article Number: e0181578 
	    Supplement: ,  
	
    
 
    
        
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            Publisher
            Public Library of Science (PLoS)
        
 
        
            Publishing Place
            Lawrence, Kan.
        
 
	
        
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        Reviewing status
        Peer reviewed
    
 
     
    
        POF-Topic(s)
        30202 - Environmental Health
    
 
    
        Research field(s)
        Lung Research
    
 
    
        PSP Element(s)
        G-503100-005
    
 
    
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        Erfassungsdatum
        2017-07-26