Abstract:
:The yellow fever vaccines (YF-17D-204 and 17DD) are considered to be among the safest vaccines and the presence of neutralizing antibodies is correlated with protection, although other immune effector mechanisms are known to be involved. T-cell responses are known to play an important role modulating antibody production and the killing of infected cells. However, little is known about the repertoire of T-cell responses elicited by the YF-17DD vaccine in humans. In this report, a library of 653 partially overlapping 15-mer peptides covering the envelope (Env) and nonstructural (NS) proteins 1 to 5 of the vaccine was utilized to perform a comprehensive analysis of the virus-specific CD4(+) and CD8(+) T-cell responses. The T-cell responses were screened ex-vivo by IFN-γ ELISPOT assays using blood samples from 220 YF-17DD vaccinees collected two months to four years after immunization. Each peptide was tested in 75 to 208 separate individuals of the cohort. The screening identified sixteen immunodominant antigens that elicited activation of circulating memory T-cells in 10% to 33% of the individuals. Biochemical in-vitro binding assays and immunogenetic and immunogenicity studies indicated that each of the sixteen immunogenic 15-mer peptides contained two or more partially overlapping epitopes that could bind with high affinity to molecules of different HLAs. The prevalence of the immunogenicity of a peptide in the cohort was correlated with the diversity of HLA-II alleles that they could bind. These findings suggest that overlapping of HLA binding motifs within a peptide enhances its T-cell immunogenicity and the prevalence of the response in the population. In summary, the results suggests that in addition to factors of the innate immunity, "promiscuous" T-cell antigens might contribute to the high efficacy of the yellow fever vaccines.
journal_name
PLoS Negl Trop Disjournal_title
PLoS neglected tropical diseasesauthors
de Melo AB,Nascimento EJ,Braga-Neto U,Dhalia R,Silva AM,Oelke M,Schneck JP,Sidney J,Sette A,Montenegro SM,Marques ETdoi
10.1371/journal.pntd.0001938subject
Has Abstractpub_date
2013-01-01 00:00:00pages
e1938issue
1eissn
1935-2727issn
1935-2735pii
PNTD-D-11-00827journal_volume
7pub_type
杂志文章abstract:BACKGROUND:Treatment needs for Schistosoma haematobium are commonly evaluated using urine filtration with detection of parasite eggs under a microscope. A common symptom of S. haematobium is hematuria, the passing of blood in urine. Hence, the use of hematuria-based diagnostic techniques as a proxy for the assessment o...
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