Відмінності між версіями «Peptides (Figs. 4D, 4E). The CE-specific cytotoxic T cell responses (granzyme»

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5A), and have been analyzed N identical panel of a large {number around the day of vaccination, and 2 wk later (Fig. 5B). The gag pDNA booster vaccination increased the magnitude from the CE-specific responses significantly (p = 0.031, paired t test), reaching as much as 1.five IFN-g+ T cells, preserving the distribution among the CD4 and CD8 T cell responses induced by CE priming (Fig. 5C). (A) The full-length p57Gag precursor protein contains the p19Gag matrix protein, the p27Gag capsid protein, and the C terminal p15Gag processing intermediate. The SIV p27CE1 and p27CE2 proteins are composed of seven conserved components (CE) derived from the p27Gag sequence, spanning 124 aa and collinearly arranged and separated via 2 aa linkers within the order shown in the cartoon.Peptides (Figs. 4D, 4E). The CE-specific cytotoxic T cell responses (granzyme B+) had been compared with these induced by the subgroup of gag pDNA vaccinated animals, which showed good CE responses (Fig. 2A). We located a substantial enhance (p = 0.018) in the frequency of CE-specific granzyme B+ T cells induced by the p27CE pDNA vaccine (Fig. 4F). We additional noted that the gag pDNA vaccine induced a wider array of cytotoxic CE-specific T cells than the p27CE vaccine. Interestingly, the frequency of cytotoxic CE-specific responses correlated (p = 0.002; Supplemental Fig. two) with the amount of the CE-specific CD8+ T cell responses in gag pDNA vaccinated macaques, supporting the notion of an association of CE responses and cytotoxicity. This locating, together with the potent induction of cytotoxic T cell responses in all of the p27CE pDNA vaccinated macaques, supports the conclusion that vaccination with p27CEThe Journal of ImmunologyFIGURE 2. Cellular responses in gag pDNA vaccinated macaques. (A) PBMC from rhesus macaques (n = 31) immunized with pDNA encoding the full-length SIV p57Gag protein had been analyzed by flow cytometry for Ag-specific responses targeting the comprehensive p27Gag (gray bars) protein or epitopes encoded by the CE (red bars). The values are plotted by decreasing p27Gag T cell responses and sorted according to the presence (n = 18) or absence (n = 13) of CE responses. Of note, animals P516 and P517 were analyzed with a peptide pool covering p39Gag that spans both the N terminal p19Gag plus the p27Gag. (B) p27Gag-specific T cell responses have been evaluated for their cytotoxic possible. The frequency of granzyme B+ Gag-specific T cells was determined among IFN-g roducing p27 Gag T cells comparing the subgroup of gag pDNA immunized macaques with (n = 18) and without (n = 13) CE-specific responses. The median and p values (t test) are indicated.pDNA induces robust CTL responses recognizing subdominant epitopes and elicits T cell responses of higher functionality than a full-length gag pDNA vaccine. Optimized CE pDNA prime-boost vaccine regimens boost CE immunogenicity In an work to boost the potency of CE recognition, two different vaccine regimens were compared using the SIV p27CE pDNA as a prime (Fig. five): 1) booster vaccination with gag pDNA [by analogy to HIV CE pDNA prime-gag pDNA boost study (21)], and two)booster vaccination with codelivery of a mixture of CE+gag pDNA. To test the initial concept, six SIV p27CE pDNA primed animals received a booster vaccination with gag pDNA right after a two mo rest (Fig.