Data from: Human circulating antibody-producing B cell as a predictive measure of mucosal immunity to poliovirus

Background: The "gold standard" for assessing mucosal immunity after vaccination with poliovirus vaccines consists in measuring virus excretion in stool after challenge with oral poliovirus vaccine (OPV). This testing is time and resource intensive, and development of alternative methods is a priority for accelerating polio eradication. We therefore evaluated circulating antibody-secreting cells (ASCs) as a potential means to evaluate mucosal immunity to poliovirus vaccine. Methods: 199 subjects, aged 10 years, and previously immunized repeatedly with OPV, were selected. Subjects were assigned to receive either a booster dose of inactivated poliovirus vaccine (IPV), bivalent OPV (bOPV), or no vaccine. Using a micro-modified whole blood-based ELISPOT assay designed for field setting, circulating poliovirus type-specific IgA- and IgG-ASCs, including gut homing ?4?7+ ASCs, were enumerated on days 0 and 7 after booster immunization. In addition, serum samples collected on days 0, 28 and 56 were tested for neutralizing antibody titers against poliovirus types 1, 2, and 3. Stool specimens were collected on day 28 (day of bOPV challenge), and on days 31, 35 and 42 and processed for poliovirus isolation. Results: An IPV dose elicited blood IgA- and IgG-ASC responses in 84.8 to 94.9% of subjects, respectively. In comparison, a bOPV dose evoked corresponding blood ASC responses in 20.0 to 48.6% of subjects. A significant association was found between IgA- and IgG-ASC responses and serum neutralizing antibody titers for poliovirus type 1, 2, 3 (p<0.001). In the IPV group, ?4?7+ ASCs accounted for a substantial proportion of IgA-ASCs and the proportion of subjects with a positive ?4?7+ IgA-ASC response to poliovirus types 1, 2 and 3 was 62.7%, 89.8% and 45.8%, respectively. A significant association was observed between virus excretion and ?4?7+ IgA- and/or IgG-ASC responses to poliovirus type 3 among immunized children; however, only a weak association was found for type 1 poliovirus. Discussion: Our results suggest that virus-specific blood ASCs, especially for type 3 poliovirus, can serve as surrogate of mucosal immunity after vaccination. Further studies are needed to evaluate the duration of such memory responses and to assess the programmatic utility of this whole blood-based mucosal ASC testing for the polio eradication program.

背景：评估脊髓灰质炎疫苗接种后黏膜免疫的金标准，是在口服脊髓灰质炎疫苗（oral poliovirus vaccine, OPV）攻毒后检测粪便中的病毒排泄情况。该检测方法耗时且耗费资源，因此开发替代检测手段是加速脊髓灰质炎根除工作的优先事项。本研究因此评估了循环抗体分泌细胞（antibody-secreting cells, ASCs）作为评估脊髓灰质炎疫苗黏膜免疫的潜在手段。

方法：本研究纳入199名10岁、既往曾多次接种OPV的受试者，将其随机分配至三组：分别接种一剂加强型灭活脊髓灰质炎疫苗（inactivated poliovirus vaccine, IPV）、二价口服脊髓灰质炎疫苗（bivalent OPV, bOPV），或不接种疫苗。本研究采用专为现场环境设计的微改良全血酶联免疫斑点（enzyme-linked immunospot, ELISPOT）检测法，在加强免疫后第0天和第7天，对循环的脊髓灰质炎病毒型别特异性IgA和IgG型ASCs（包括肠道归巢α4β7+ ASCs）进行计数。此外，本研究对第0、28和56天采集的血清样本进行了检测，以分析针对脊髓灰质炎病毒1、2、3型的中和抗体滴度。分别在第28天（即bOPV攻毒当日）及第31、35、42天收集粪便样本，用于脊髓灰质炎病毒分离检测。

结果：接种一剂IPV后，分别有84.8%至94.9%的受试者出现血液IgA型和IgG型ASC应答。相比之下，接种一剂bOPV后，仅20.0%至48.6%的受试者出现相应的血液ASC应答。研究发现，针对脊髓灰质炎病毒1、2、3型的IgA型和IgG型ASC应答与血清中和抗体滴度之间存在显著相关性（p<0.001）。在IPV组中，α4β7+ ASCs在IgA型ASCs中占比可观；针对脊髓灰质炎病毒1、2、3型，出现α4β7+ IgA型ASC阳性应答的受试者占比分别为62.7%、89.8%和45.8%。免疫接种的受试者中，脊髓灰质炎病毒3型的粪便排毒情况与α4β7+ IgA型和/或IgG型ASC应答之间存在显著相关性；但针对1型脊髓灰质炎病毒，仅存在较弱的相关性。

讨论：本研究结果表明，病毒特异性血液ASCs（尤其是针对3型脊髓灰质炎病毒）可作为疫苗接种后黏膜免疫的替代标志物。未来仍需开展进一步研究，以评估此类记忆应答的持续时间，并评估这种全血基础的黏膜ASC检测方法在脊髓灰质炎根除计划中的项目应用价值。