HPV Immunology and HPV Serology Laboratories, Frederick National Laboratory for Cancer Research, Frederick, MD, United States.
Weill Cornell Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York, NY, United States.
Vaccine. 2019 Apr 24;37(18):2502-2510. doi: 10.1016/j.vaccine.2019.03.034. Epub 2019 Mar 30.
Duration and functional aspects of the oral and systemic antibody responses following HPV vaccination in HIV-negative (HIV) and HIV-positive (HIV) men are not well characterized. Oral and systemic HPV-16 and HPV-18-specific antibody levels were evaluated over 18-months of follow-up, in HIV and HIV men. Sera and oral gargles from 147 HIV men, ages 27-45 and 75 HIV men, ages 22-61, who received 3-doses of quadrivalent HPV vaccine were tested for HPV-16 and HPV-18 antibodies at Day 1, Month 7 (1 month post-dose 3), and Month 18 (12 months post-dose 3) and HPV avidity (Day 1, and Month 7) using L1-VLP ELISA. All individuals seroconverted, regardless of HIV-status, following 3-doses of vaccine for HPV-16 and HPV-18. Serum HPV-16 and HPV-18 antibody geometric mean levels were >2-fold lower in HIV compared to HIV men at Month 7 (HPV-16: 808.5 versus 2119.8 EU/mL, and HPV-18: 285.8 versus 611.6 EU/mL, p < 0.001) but not significantly different at Month 18 (HPV-16: 281.8 versus 359.7 EU/mL, p = 0.145, and HPV-18: 120.2 versus 93.4 EU/mL, p = 0.372). Post-vaccination, only oral HPV-16 antibody levels at Month 7 were significantly different between HIV and HIV men (127.7 versus 177.1 EU/mg of IgG, p = 0.008). Among baseline HPV-seronegative men, circulating levels of HPV-16 and HPV-18 antibodies were up to >3 fold lower in HIV men, at Months 7 and 18. In contrast, levels of HPV-16 and HPV-18 antibodies after vaccination were not inferior in baseline HPV-seropositive, HIV men. HPV-16 and HPV-18 avidity was lower among HIV compared to HIV men at Month 7 (HPV-16: 1.95 M versus 2.12 M, p = 0.027; HPV-18: 1.50 M versus 1.72 M, p < 0.001). Although differences in peak antibody levels were observed between HIV and HIV men following 3 doses of vaccine, plateau antibody levels were overall comparable, and avidity was relatively high for both groups. These data indicate that the vaccine induced antibody affinity maturation in both HIV and HIV men and will likely result in long-term protective immune responses.
在 HIV 阴性(HIV)和 HIV 阳性(HIV)男性中, HPV 疫苗接种后口腔和全身抗体的持续时间和功能方面尚未得到很好的描述。在 18 个月的随访中,评估了 147 名年龄在 27-45 岁的 HIV 男性和 75 名年龄在 22-61 岁的 HIV 男性的口腔和全身 HPV-16 和 HPV-18 特异性抗体水平。接受 3 剂四价 HPV 疫苗的 147 名 HIV 男性和 75 名 HIV 男性在第 1 天、第 7 个月(第 3 剂后 1 个月)和第 18 个月(第 3 剂后 12 个月)以及 HPV 亲和力(第 1 天和第 7 个月)时,使用 L1-VLP ELISA 检测 HPV-16 和 HPV-18 抗体。所有个体均在接受 3 剂疫苗后针对 HPV-16 和 HPV-18 发生血清转化,无论 HIV 状态如何。与 HIV 男性相比,在第 7 个月时,血清 HPV-16 和 HPV-18 抗体几何平均水平在 HIV 男性中低 2 倍以上(HPV-16:808.5 对 2119.8 EU/mL,HPV-18:285.8 对 611.6 EU/mL,p < 0.001),但在第 18 个月时无显著差异(HPV-16:281.8 对 359.7 EU/mL,p = 0.145,HPV-18:120.2 对 93.4 EU/mL,p = 0.372)。接种疫苗后,只有第 7 个月时 HIV 和 HIV 男性之间的口腔 HPV-16 抗体水平存在显著差异(127.7 对 177.1 EU/mg IgG,p = 0.008)。在基线 HPV 血清阴性的男性中,在第 7 个月和第 18 个月时,HPV-16 和 HPV-18 抗体的循环水平在 HIV 男性中低了 3 倍以上。相比之下,在基线 HPV 血清阳性的 HIV 男性中,接种疫苗后 HPV-16 和 HPV-18 抗体的水平没有降低。与 HIV 男性相比,HPV-16 和 HPV-18 亲和力在第 7 个月时较低(HPV-16:1.95 M 对 2.12 M,p = 0.027;HPV-18:1.50 M 对 1.72 M,p < 0.001)。尽管在接种 3 剂疫苗后观察到 HIV 和 HIV 男性之间的峰值抗体水平存在差异,但总体而言,抗体水平达到平台期后相当,并且两组的亲和力相对较高。这些数据表明,疫苗在 HIV 和 HIV 男性中诱导了抗体亲和力成熟,并且可能导致长期的保护性免疫反应。