Emeny Rebecca T, Wheeler Cosette M, Jansen Kathrin U, Hunt William C, Fu Tong-Ming, Smith Judith F, MacMullen Stefani, Esser Mark T, Paliard Xavier
Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131-5276, USA.
J Virol. 2002 Aug;76(15):7832-42. doi: 10.1128/jvi.76.15.7832-7842.2002.
In this study, we evaluated the potency of a human papillomavirus (HPV) virus-like particle (VLP)-based vaccine at generating HPV type 11 (HPV-11)-specific cellular and humoral immune responses in seronegative women. The vaccine was administered by intramuscular immunizations at months 0, 2, and 6. A fourth immunization was administered to approximately half of the women at month 12. All vaccine recipients had positive HPV-11 VLP-specific lymphoproliferative responses at month 3 following the second immunization (geometric mean lymphoproliferative stimulation index [SI] = 28.4; 95% confidence interval [CI] = 16.9 to 48.0) and HPV-11 VLP-specific antibody titers following the first immunization at month 1 (geometric mean antibody titer = 53.9 milli-Merck units/ml, 95% CI, 34.8 to 83.7). In contrast, lymphoproliferative and antibody titer responses were never detected in the participants who received placebo. Relatively homogeneous lymphoproliferative responses were observed in all vaccinated women. The mean lymphoproliferative SI of the vaccinated group over the first 12 months of the study was 7.6-fold greater than that of the placebo group following the initial immunization. The cellular immune responses generated by VLP immunization were both Th1 and Th2, since peripheral blood mononuclear cells from vaccinees, but not placebo recipients, secreted interleukin 2 (IL-2), IL-5, and gamma interferon (IFN-gamma) in response to in vitro stimulation with HPV-11 VLP. The proliferation-based SI was moderately correlated with IFN-gamma production and significantly correlated with IL-2 production after the third immunization (P = 0.078 and 0.002, respectively). The robust lymphoproliferative responses were specific for HPV-11, since SIs generated against bovine papillomavirus and HPV-16 VLPs were not generally observed and when detected were similar pre- and postimmunization.
在本研究中，我们评估了一种基于人乳头瘤病毒（HPV）病毒样颗粒（VLP）的疫苗在血清阴性女性中产生11型HPV（HPV-11）特异性细胞免疫和体液免疫反应的效力。该疫苗在第0、2和6个月通过肌肉注射进行免疫接种。约一半的女性在第12个月接受了第四次免疫接种。所有疫苗接种者在第二次免疫接种后第3个月时，HPV-11 VLP特异性淋巴细胞增殖反应呈阳性（几何平均淋巴细胞增殖刺激指数[SI]=28.4；95%置信区间[CI]=16.9至48.0），且在第1个月首次免疫接种后有HPV-11 VLP特异性抗体滴度（几何平均抗体滴度=53.9毫微克/毫升，95%CI，34.8至83.7）。相比之下，接受安慰剂的参与者中从未检测到淋巴细胞增殖和抗体滴度反应。在所有接种疫苗的女性中观察到相对均匀的淋巴细胞增殖反应。在研究的前12个月中，接种疫苗组的平均淋巴细胞增殖SI比初次免疫接种后安慰剂组高7.6倍。VLP免疫接种产生的细胞免疫反应既有Th1型也有Th2型，因为疫苗接种者而非安慰剂接受者的外周血单个核细胞在体外受到HPV-11 VLP刺激后会分泌白细胞介素2（IL-2）、IL-5和γ干扰素（IFN-γ）。第三次免疫接种后，基于增殖的SI与IFN-γ产生呈中度相关，与IL-2产生呈显著相关（P分别为0.078和0.002）。强劲的淋巴细胞增殖反应对HPV-11具有特异性，因为针对牛乳头瘤病毒和HPV-16 VLP产生的SI通常未观察到，即便检测到，免疫前后也相似。
