Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Infections and Cancer Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
J Infect Dis. 2021 Jun 4;223(11):1992-2000. doi: 10.1093/infdis/jiaa617.
Human papillomaviruses (HPV) cause several human cancers. Bivalent (Cervarix) and quadrivalent (qGardasil) HPV vaccines both contain virus-like particles of the major oncogenic HPV types 16 and 18, but also cross-protect against some nonvaccine types. However, data on long-term sustainability of the cross-reactive antibody responses to HPV vaccines are scarce.
Serum samples donated 7-12 years after immunization at age 16-17 years with bivalent (n = 730) or quadrivalent (n = 337) HPV vaccine were retrieved from the population-based Finnish Maternity Cohort biobank. Serum antibody levels against HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, and 73 were determined using multiplex pseudovirion binding assay. Antibody avidity was assessed using ammonium thiocyanate treatment.
Seropositivity for HPV31, 33, 35, 45, 51, 52, 58, 59, 68, and 73 was increasingly common (P ≤ .001; χ 2 test for trend for each of these types) when women had high anti-HPV16 antibody levels. For 8 nonvaccine HPV types seropositivity was more common among recipients of bivalent than quadrivalent vaccine, in particular for HPV31, 35, 45, 51, 52, and 58 (P < .001). Antibody avidity was higher in the quadrivalent vaccine recipients for HPV6, 11, and two of the nonvaccine types, but lower for HPV16 and 18 (P < .001).
Both vaccines elicit cross-reactive antibodies detectable even 12 years after vaccination. Cross-reactive seropositivity is more common in women with high anti-HPV16 antibody response and in the bivalent vaccine recipients.
人乳头瘤病毒(HPV)可引发多种人类癌症。二价(Cervarix)和四价(qGardasil)HPV 疫苗均包含主要致癌 HPV 类型 16 和 18 的病毒样颗粒,但也对一些非疫苗类型具有交叉保护作用。然而,HPV 疫苗的交叉反应性抗体反应的长期可持续性数据却很少。
从基于人群的芬兰母婴队列生物库中检索了 16-17 岁时接种二价(n=730)或四价(n=337)HPV 疫苗后 7-12 年捐赠的血清样本。使用多重假病毒结合测定法测定针对 HPV 类型 6、11、16、18、31、33、35、39、45、51、52、56、58、59、68 和 73 的血清抗体水平。使用硫氰酸铵处理评估抗体亲和力。
当女性具有高抗 HPV16 抗体水平时,HPV31、33、35、45、51、52、58、59、68 和 73 的血清阳性率(P≤.001;针对每种类型的 χ²趋势检验)不断增加。与四价疫苗相比,二价疫苗接种者中,8 种非疫苗 HPV 类型的血清阳性率更高,尤其是 HPV31、35、45、51、52 和 58(P<.001)。四价疫苗接种者针对 HPV6、11 和两种非疫苗类型的抗体亲和力较高,但针对 HPV16 和 18 的抗体亲和力较低(P<.001)。
两种疫苗都能产生可在接种 12 年后检测到的交叉反应性抗体。在具有高抗 HPV16 抗体反应的女性和二价疫苗接种者中,交叉反应性血清阳性更为常见。