Division of Translational Vaccine Research, Beckman Research Institute of the City of Hope, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
J Infect Dis. 2012 Apr 15;205(8):1294-304. doi: 10.1093/infdis/jis107. Epub 2012 Mar 7.
It has been reported that cytomegalovirus (CMV) pp65-specific T cells can protect hematopoietic cell transplant (HCT) recipients from CMV complications. Two candidate CMV peptide vaccines composed of the HLA A0201 pp65(495-503) cytotoxic CD8(+) T-cell epitope fused to 2 different universal T-helper epitopes (either the synthetic Pan DR epitope [PADRE] or a natural Tetanus sequence) were clinically evaluated for safety and ability to elicit pp65 T cells in HLA A0201 healthy volunteers.
Escalating doses (0.5, 2.5, 10 mg) of PADRE or Tetanus pp65(495-503) vaccines with (30 adults) or without (28 adults) PF03512676 adjuvant were administered by subcutaneous injection every 3 weeks for a total of 4 injections.
No serious adverse events were reported, although vaccines used in combination with PF03512676 had enhanced reactogenicity. Ex vivo responses were detected by flow cytometry exclusively in volunteers who received the vaccine coadministered with PF03512676. In addition, using a sensitive in vitro stimulation system, vaccine-elicited pp65(495-503) T cells were expanded in 30% of volunteers injected solely with the CMV peptides and in all tested subjects receiving the vaccines coinjected with PF03512676.
Acceptable safety profiles and vaccine-driven expansion of pp65(495-503) T cells in healthy adults support further evaluation of CMV peptide vaccines combined with PF03512676 in the HCT setting.
NCT00722839.
据报道，巨细胞病毒 (CMV) pp65 特异性 T 细胞可保护造血细胞移植 (HCT) 受者免受 CMV 并发症的影响。两种候选 CMV 肽疫苗由 HLA A0201 pp65(495-503)细胞毒性 CD8(+) T 细胞表位与 2 种不同的通用 T 辅助表位（合成 Pan DR 表位 [PADRE] 或天然破伤风序列）融合而成，已在 HLA A0201 健康志愿者中进行了临床安全性评估和诱导 pp65 T 细胞的能力。
递增剂量（0.5、2.5、10mg）的 PADRE 或 Tetanus pp65(495-503)疫苗与（30 名成年人）或不与（28 名成年人）PF03512676 佐剂联合通过皮下注射，每 3 周注射 1 次，共注射 4 次。
未报告严重不良事件，尽管与 PF03512676 联合使用的疫苗具有增强的反应原性。通过流式细胞术仅在接受与 PF03512676 联合使用疫苗的志愿者中检测到体外反应。此外，使用灵敏的体外刺激系统，在仅接受 CMV 肽注射的志愿者中，30%的志愿者和所有接受与 PF03512676 联合注射疫苗的测试对象中，均扩增了疫苗诱导的 pp65(495-503)T 细胞。
在健康成年人中，可接受的安全性和疫苗驱动的 pp65(495-503)T 细胞扩增支持进一步评估与 PF03512676 联合使用的 CMV 肽疫苗在 HCT 环境中的应用。
NCT00722839。
