Leonova I V, Leonov S V, Waris M, Russi J C, Grandien M, Norrby E
Swedish Institute for Infectious Disease Control, Stockholm, Sweden.
J Clin Virol. 1998 Aug 20;11(2):137-47. doi: 10.1016/s1386-6532(98)00045-2.
The successful development of an RSV vaccine requires a better understanding of the pathogenesis of primary infection, susceptibility to reinfection, and the immunopathology of enhanced illness in children immunized with a non-replicating RSV candidate vaccine. The exact role of different immune parameters in RSV pathogenesis remains controversial.
To study the contribution of antibodies directed to the linear antigenic and immunogenic regions of the N and P proteins in the titer rise and avidity maturation of total anti-RSV antibodies.
The occurrence of antibodies directed against three linear antigenic and immunogenic regions in each of the nucleocapsid (N): N3 (Thr11 to Gly30), N25 (Ser231 to Ala250) and N39 (Thr371 to Leu391), and the phospho-(P) proteins of respiratory syncytial virus (RSV), subgroup A: P49 (Pro91 to Asp110), P56 (Ser161 to Lys180) and P62 (Glu221 to Phe241), were analyzed in ELISA with (a) 32 paired sera from humans with recent or previous RSV subgroup A and/or B infection diagnosed by conventional ELISA, detection of antigen in nasopharyngeal aspirates and measurement of antibody avidity change; and (b) 40 RSV antibody-positive sera (HCS) obtained from patients during their convalescence from RSV infection and possessing clearly demonstrable titers of RSV IgG in conventional enzyme immunoassays (EIA) based on whole RSV antigen.
The titer rise of antibodies directed to the combined three peptides representing the RSV N protein was well correlated with the rise in anti-RSV antibodies measured in whole antigen ELISA. Surprisingly, the rise in antibodies against a truncated main C-terminal epitope (Gln381 to Leu391) of the N protein (represented by subgroup A specific sequence of the N39/1 peptide) was inversely correlated with the titer rise of total anti-RSV antibodies. The titer rise of antibodies to the C-terminal linear site of the RSV N (N39/1) protein was subgroup-specific during the course of primary RSV infection. A titer rise in antibodies to the C-terminal linear sites of RSV N (i.e. N39/1) and P (P62) proteins had a dominating appearance in sera from newborn infants (6-7 months) and from patients with RSV reinfections. Anti-RSV antibody titers of late convalescent sera correlated with the titers of antibodies directed to the C-terminal linear site of RSV P (P62) protein. The avidity maturation of the anti-RSV immune response followed the titer rise of anti-P62 antibodies during the course of primary or secondary RSV infection.
呼吸道合胞病毒（RSV）疫苗的成功研发需要更好地了解初次感染的发病机制、再感染易感性以及用非复制型RSV候选疫苗免疫的儿童中病情加重的免疫病理学。不同免疫参数在RSV发病机制中的确切作用仍存在争议。
研究针对N和P蛋白线性抗原和免疫原性区域的抗体在总抗RSV抗体滴度升高和亲和力成熟中的作用。
分析针对呼吸道合胞病毒（RSV）A亚组核衣壳（N）蛋白的三个线性抗原和免疫原性区域（N3：苏氨酸11至甘氨酸30、N25：丝氨酸231至丙氨酸250、N39：苏氨酸371至亮氨酸391）以及磷蛋白（P）的抗体的产生情况，P蛋白的三个区域为：P49（脯氨酸91至天冬氨酸110）、P56（丝氨酸161至赖氨酸180）和P62（谷氨酸221至苯丙氨酸241），采用酶联免疫吸附测定（ELISA）进行分析，具体如下：（a）32对来自近期或既往感染过RSV A和/或B亚组的人类血清，通过传统ELISA诊断、检测鼻咽抽吸物中的抗原以及测量抗体亲和力变化；（b）40份RSV抗体阳性血清（恢复期血清），这些血清来自RSV感染恢复期的患者，并且在基于全RSV抗原的传统酶免疫测定（EIA）中具有明显可检测到的RSV IgG滴度。
针对代表RSV N蛋白的三种组合肽的抗体滴度升高与全抗原ELISA中测得的抗RSV抗体升高密切相关。令人惊讶的是，针对N蛋白截短的主要C末端表位（谷氨酰胺381至亮氨酸391）（由N39/1肽的A亚组特异性序列代表）的抗体升高与总抗RSV抗体滴度升高呈负相关。在原发性RSV感染过程中，针对RSV N（N39/1）蛋白C末端线性位点的抗体滴度升高具有亚组特异性。针对RSV N（即N39/1）和P（P62）蛋白C末端线性位点的抗体滴度升高在新生儿（6 - 7个月）和RSV再感染患者的血清中占主导地位。恢复期晚期血清的抗RSV抗体滴度与针对RSV P（P62）蛋白C末端线性位点的抗体滴度相关。在原发性或继发性RSV感染过程中，抗RSV免疫反应的亲和力成熟跟随抗P62抗体滴度升高。
