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Primary vaccination with low dose live dengue 1 virus generates a proinflammatory,multifunctional T cell response in humans
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نویسنده
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lindow j.c. ,borochoff-porte n. ,durbin a.p. ,whitehead s.s. ,fimlaid k.a. ,bunn j.y. ,kirkpatrick b.d.
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منبع
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plos neglected tropical diseases - 2012 - دوره : 6 - شماره : 7
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چکیده
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The four dengue virus serotypes (denv-1-denv-4) have a large impact on global health,causing 50-100 million cases of dengue fever annually. herein,we describe the first kinetic t cell response to a low-dose denv-1 vaccination study (10 pfu) in humans. using flow cytometry,we found that proinflammatory cytokines,ifnγ,tnfα,and il-2,were generated by denv-1-specific cd4 + cells 21 days post-denv-1 exposure,and their production continued through the latest time-point,day 42 (p<0.0001 for all cytokines). no statistically significant changes were observed at any time-points for il-10 (p = 0.19),a regulatory cytokine,indicating that the response to denv-1 was primarily proinflammatory in nature. we also observed little t cell cross-reactivity to the other 3 denv serotypes. the percentage of multifunctional t cells (t cells making ≥2 cytokines simultaneously) increased with time post-denv-1 exposure (p<0.0001). the presence of multifunctional t cells together with neutralizing antibody data suggest that the immune response generated to the vaccine may be protective. this work provides an initial framework for defining primary t cell responses to each denv serotype and will enhance the evaluation of a tetravalent denv vaccine.
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آدرس
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vaccine testing center and unit of infectious diseases,department of medicine,university of vermont college of medicine,burlington,vt, United States, vaccine testing center and unit of infectious diseases,department of medicine,university of vermont college of medicine,burlington,vt, United States, johns hopkins bloomberg school of public health,baltimore,md, United States, laboratory of infectious diseases,national institute of allergy and infectious diseases,national institutes of health,bethesda,md, United States, vaccine testing center and unit of infectious diseases,department of medicine,university of vermont college of medicine,burlington,vt, United States, university of vermont college of mathematics,burlington,vt, United States, vaccine testing center and unit of infectious diseases,department of medicine,university of vermont college of medicine,burlington,vt, United States
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Authors
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