Toh Zheng Quan, Cheow Kathleen Wen Bei, Russell Fiona M, Hoe Edwin, Reyburn Rita, Fong James, Tuivaga Evelyn, Ratu Felisita T, Nguyen Cattram D, Matanitobua Silivia, Reitsma Andrea, Tabrizi Sepehr N, Garland Suzanne M, Mulholland Edward K, Licciardi Paul V
Murdoch Children's Research Institute, Parkville, Victoria, Australia.
Centre for International Child Health, Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.
Open Forum Infect Dis. 2018 Jun 20;5(7):ofy147. doi: 10.1093/ofid/ofy147. eCollection 2018 Jul.
This study examined the cellular immunity of 0, 1, 2, and 3 doses of Gardasil vaccine (4vHPV) in girls after 6 years and their responses to a subsequent dose of Cervarix vaccine (2vHPV).
A subset of girls (n = 59) who previously received 0, 1, 2, or 3 doses of 4vHPV 6 years earlier were randomly selected from a cohort study of Fijian girls (age 15-19 years). Blood was collected before and 28 days after a dose of 2vHPV. The HPV16- and HPV18-specific cellular immune response was determined by IFNγ-ELISPOT and by measurement of cytokines in peripheral blood mononuclear cell supernatants.
Six years after 4vHPV vaccination, HPV18-specific responses were significantly lower in the 1- (1D) or 2-dose (2D) recipients compared with 3-dose recipients (2D: IFNγ-ELISPOT: = .008; cytokines, IFNγ: = .002; IL-2: = .022; TNFα: = .016; IL-10: = .018; 1D: IL-2: = .031; IL-10: = .014). These differences were no longer significant post-2vHPV. No significant differences in HPV16 responses (except IL-2, < .05) were observed between the 2- or 1-dose recipients and 3-dose recipients.
These data suggest that cellular immunity following reduced-dose schedules was detectable after 6 years, although the responses were variable between HPV types and dosage groups. The clinical significance of this is unknown. Further studies on the impact of reduced dose schedules are needed, particularly in high-disease burden settings.
本研究检测了女孩在接种0、1、2和3剂加德西疫苗（4价人乳头瘤病毒疫苗）6年后的细胞免疫情况以及她们对后续一剂希瑞适疫苗（2价人乳头瘤病毒疫苗）的反应。
从一项针对斐济女孩（年龄15 - 19岁）的队列研究中随机选取一部分女孩（n = 59），这些女孩在6年前曾接种0、1、2或3剂4价人乳头瘤病毒疫苗。在接种一剂2价人乳头瘤病毒疫苗前及接种后28天采集血液。通过干扰素γ - 酶联免疫斑点法以及检测外周血单个核细胞上清液中的细胞因子来确定人乳头瘤病毒16型和18型特异性细胞免疫反应。
在接种4价人乳头瘤病毒疫苗6年后，与接种3剂的受种者相比，接种1剂（1D）或2剂（2D）的受种者中人乳头瘤病毒18型特异性反应显著降低（2D：干扰素γ - 酶联免疫斑点法：P = .008；细胞因子，干扰素γ：P = .002；白细胞介素 - 2：P = .022；肿瘤坏死因子α：P = .016；白细胞介素 - 10：P = .018；1D：白细胞介素 - 2：P = .031；白细胞介素 - 10：P = .014）。在接种2价人乳头瘤病毒疫苗后，这些差异不再显著。在接种2剂或1剂的受种者与接种3剂的受种者之间，未观察到人乳头瘤病毒16型反应的显著差异（白细胞介素 - 2除外，P < .05）。
这些数据表明，6年后可检测到减量接种方案后的细胞免疫，尽管不同人乳头瘤病毒类型和剂量组之间的反应存在差异。其临床意义尚不清楚。需要进一步研究减量接种方案的影响，特别是在疾病负担高的地区。
