Jacobson Mark A, Sinclair Elizabeth, Bredt Barry, Agrillo Laurie, Black Douglas, Epling C Lorrie, Carvidi Alexander, Ho Terence, Bains Raji, Adler Stuart P
Positive Health Program, Department of Medicine, University of California San Francisco, 4th Floor, 995 Potrero, San Francisco, CA 94110, USA.
J Clin Virol. 2006 Mar;35(3):332-7. doi: 10.1016/j.jcv.2005.09.019. Epub 2006 Jan 18.
Towne cytomegalovirus (CMV) vaccine is safe and immunogenic, though its protective efficacy has yet to be optimized.
Describe antigen-specific T cell responses to Towne vaccination.
3000 pfu Towne CMV vaccine were given to 12 CMV-seronegative volunteers. CMV-specific CD4+ and CD8+ T cell proliferation and IFNgamma expression were measured by flow cytometry after stimulation with CMV lysate or peptides.
All vaccinees developed CD4+ and CD8+ T cell proliferation and CD4+ T cell IFNgamma responses to multiple CMV antigens, but their CD8+ T cells had low or undetectable IFNgamma responses to pp65 peptide pool. The seven HLA-A2+ subjects had higher CD8+ T cell proliferation and IFNgamma responses to IE than pp65, and two never developed CD8+ T cell IFNgamma responses to pp65. Peak CD4+ T cell IFNgamma responses to CMV lysate were lower than values observed in natural CMV seropositives. Initial CD4+ and CD8+ T cell responses to lysate and pp65 waned after 12 months to levels that were lower than those in healthy CMV seropositives, while vaccinees' CD8+ T cell responses to IE were robust and prolonged.
Correlating CMV antigen-specific T cell responses with clinical protective efficacy may facilitate future CMV vaccine development.
汤氏巨细胞病毒(CMV)疫苗是安全且具有免疫原性的,尽管其保护效力仍有待优化。
描述针对汤氏疫苗接种的抗原特异性T细胞反应。
给12名CMV血清阴性志愿者接种3000个空斑形成单位的汤氏CMV疫苗。在用CMV裂解物或肽刺激后,通过流式细胞术测量CMV特异性CD4+和CD8+T细胞增殖以及IFNγ表达。
所有接种疫苗者均产生了针对多种CMV抗原的CD4+和CD8+T细胞增殖以及CD4+T细胞IFNγ反应,但其CD8+T细胞对pp65肽池的IFNγ反应较低或无法检测到。7名HLA-A2+受试者的CD8+T细胞对IE的增殖和IFNγ反应高于对pp65的反应,并且有2名受试者从未产生过针对pp65的CD8+T细胞IFNγ反应。CD4+T细胞对CMV裂解物的IFNγ反应峰值低于在天然CMV血清阳性者中观察到的值。最初对裂解物和pp65的CD4+和CD8+T细胞反应在12个月后减弱至低于健康CMV血清阳性者的水平,而接种疫苗者的CD8+T细胞对IE的反应强烈且持久。
将CMV抗原特异性T细胞反应与临床保护效力相关联可能有助于未来CMV疫苗的开发。