Centre for Infectious Disease and Control (Clb), National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
PLoS One. 2011;6(11):e27681. doi: 10.1371/journal.pone.0027681. Epub 2011 Nov 14.
Whooping cough is a respiratory disease caused by Bordetella pertussis, which induces mucosal IgA antibodies that appear to be relevant in protection. Serum IgA responses are measured after pertussis infection and might provide an additional role in pertussis diagnostics. However, the possible interfering role for pertussis vaccinations in the induction of serum IgA antibodies is largely unknown.
METHODS/PRINCIPAL FINDINGS: We compared serum IgA responses in healthy vaccinated children between 1 and 10 years of age with those in children who despite vaccinations recently were infected with Bordetella pertussis. All children have been vaccinated at 2, 3, 4 and 11 months of age with either the Dutch whole-cell pertussis (wP) vaccine or an acellular pertussis (aP) vaccine and additionally received an aP booster vaccination at 4 years of age. Serum IgA responses to pertussis toxin (PT), filamentous heamagglutinin (FHA) and pertactin (Prn) were measured with a fluorescent multiplex bead-based immuno-assay. An ELISPOT-assay was used for the detection of IgA-memory B-cells specific to these antigens. Serum IgA levels to all pertussis vaccine antigens were significantly higher in infected children compared with healthy children. High correlations between anti-PT, anti-FHA or anti-Prn IgA and IgG levels were found in infected children and to some degree in wP primed children, but not at all in aP primed children. Highest numbers of IgA-pertussis-specific memory B-cells were observed after infection and generally comparable numbers were found after wP and aP vaccination.
This study provides new insight in the diagnostic role for serum IgA responses against PT in vaccinated children. Since aP vaccines induce high serum IgG levels that interfere with pertussis diagnostics, serum IgA-PT levels will provide an additional diagnostic role. High levels of serum IgA for PT proved specific for recent pertussis infection with reasonable sensitivity, whereas the role for IgA levels against FHA and Prn in diagnosing pertussis remains controversial.
百日咳是由博德特氏菌引起的呼吸道疾病，它诱导黏膜 IgA 抗体，这些抗体似乎与保护作用有关。在百日咳感染后测量血清 IgA 反应，可能在百日咳诊断中提供额外的作用。然而，百日咳疫苗接种在诱导血清 IgA 抗体方面的可能干扰作用在很大程度上尚不清楚。
方法/主要发现：我们比较了 1 至 10 岁健康接种儿童与最近感染博德特氏菌的儿童之间的血清 IgA 反应。所有儿童均在 2、3、4 和 11 个月大时接种了荷兰全细胞百日咳（wP）疫苗或无细胞百日咳（aP）疫苗，并在 4 岁时额外接种了 aP 加强疫苗。使用荧光多重微珠免疫测定法测量对百日咳毒素（PT）、丝状血凝素（FHA）和 pertactin（Prn）的血清 IgA 反应。使用 ELISPOT 测定法检测针对这些抗原的 IgA 记忆 B 细胞。与健康儿童相比，感染儿童的血清 IgA 水平对所有百日咳疫苗抗原均显著升高。在感染儿童中发现抗-PT、抗-FHA 或抗-Prn IgA 和 IgG 水平之间存在高度相关性，在 wP 初免儿童中存在一定程度的相关性，但在 aP 初免儿童中则完全没有相关性。在感染后观察到最高数量的 IgA-百日咳特异性记忆 B 细胞，并且在 wP 和 aP 接种后通常发现相当数量的记忆 B 细胞。
本研究为疫苗接种儿童血清 IgA 反应对 PT 的诊断作用提供了新的见解。由于 aP 疫苗诱导高水平的血清 IgG，干扰了百日咳的诊断，因此血清 IgA-PT 水平将提供额外的诊断作用。PT 血清 IgA 水平高证明对近期百日咳感染具有特异性，且具有合理的敏感性，而 IgA 水平对 FHA 和 Prn 在诊断百日咳中的作用仍存在争议。
