Peptides (Figs. 4D, 4E). The CE-specific cytotoxic T cell responses (granzyme

Матеріал з HistoryPedia
Перейти до: навігація, пошук

The starting with chromosome 1). Good values indicate the CE-specific cytotoxic T cell responses (granzyme B+) have been compared with these induced by the subgroup of gag pDNA vaccinated animals, which showed optimistic CE responses (Fig. Optimized CE pDNA prime-boost vaccine regimens raise CE immunogenicity In an effort to enhance the potency of CE recognition, two different vaccine regimens have been compared using the SIV p27CE pDNA as a prime (Fig. 5): 1) booster vaccination with gag pDNA [by analogy to HIV CE pDNA prime-gag pDNA enhance study (21)], and 2)booster vaccination with codelivery of a mixture of CE+gag pDNA. To test the initial idea, six SIV p27CE pDNA primed animals received a booster vaccination with gag pDNA just after a two mo rest (Fig. 5A), and were analyzed around the day of vaccination, and two wk later (Fig. 5B). The gag pDNA booster vaccination increased the magnitude of your CE-specific responses significantly (p = 0.031, paired t test), reaching as much as 1.five IFN-g+ T cells, keeping the distribution amongst the CD4 and CD8 T cell responses induced by CE priming (Fig. 5C). 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 two aa linkers inside the order shown in the cartoon.Peptides (Figs. 4D, 4E). The CE-specific cytotoxic T cell responses (granzyme B+) were compared with those induced by the subgroup of gag pDNA vaccinated animals, which showed constructive CE responses (Fig. 2A). We found a significant boost (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 range of cytotoxic CE-specific T cells than the p27CE vaccine. Interestingly, the frequency of cytotoxic CE-specific responses correlated (p = 0.002; Supplemental Fig. 2) 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 all 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 were analyzed by flow cytometry for Ag-specific responses targeting the total p27Gag (gray bars) protein or epitopes encoded by the CE (red bars). The values are plotted by decreasing p27Gag T cell responses and sorted based on 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 each the N terminal p19Gag and the p27Gag. (B) p27Gag-specific T cell responses were evaluated for their cytotoxic prospective. The frequency of granzyme B+ Gag-specific T cells was determined amongst IFN-g roducing p27 Gag T cells comparing the subgroup of gag pDNA immunized macaques with (n = 18) and without having (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 greater functionality than a full-length gag pDNA vaccine.