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活呼吸道合胞病毒启动对候选重组疫苗BBG2Na产生的免疫反应的影响

Influence of live respiratory syncytial virus priming on the immune response generated by a recombinant vaccine candidate, BBG2Na.

作者信息

Goestch L, Plotnicky-Gilquin H, Champion T, Beck A, Haeuw J F, Nguyen T, Bonnefoy J Y, Corvaïa N

机构信息

Centre d'Immunologie Pierre Fabre, 5 Av. Napoléon III, 74164 St Julien en Genevois, France.

出版信息

Vaccine. 2000 Jun 1;18(24):2648-55. doi: 10.1016/s0264-410x(00)00064-5.

Abstract

Respiratory syncytial virus is one of the major respiratory pathogens for infants and immunocompromized children. With the exception of young children, all the population has encountered RSV and is seropositive. Recent reports have demonstrated however that the virus also affects the elderly and represents a major cause of illness associated with an excess of morbidity and mortality. We have generated a recombinant RSV vaccine, BBG2Na, which is highly protective in rodents against RSV infection. The aim of this study was to evaluate the ability of the vaccine to increase anti-RSV protection in RSV-primed mice and to characterize the induced immune responses. Immunization with BBG2Na increased the anti-RSV-A serum antibody titers of RSV-primed mice with induction of both IgG1 and IgG2a antibodies attesting for a mixed Th response. Moreover, the level of the induced anti-G2Na antibodies was greater in seropositive mice. Finally, sera from RSV-primed mice displayed a higher protective efficacy after transfer into naive mice following subsequent immunization with BBG2Na than sera of mice immunized with RSV-A only. Our results demonstrate that BBG2Na is immunogenic and increases the protective efficacy of serum antibodies in RSV-primed mice; they support the possibility of performing clinical trials in the seropositive human population.

摘要

呼吸道合胞病毒是婴幼儿和免疫功能低下儿童的主要呼吸道病原体之一。除幼儿外,所有人群都曾接触过呼吸道合胞病毒且血清呈阳性。然而,最近的报告表明,该病毒也会影响老年人,并且是导致发病率和死亡率过高相关疾病的主要原因。我们制备了一种重组呼吸道合胞病毒疫苗BBG2Na,它在啮齿动物中对呼吸道合胞病毒感染具有高度保护作用。本研究的目的是评估该疫苗在经呼吸道合胞病毒致敏的小鼠中增强抗呼吸道合胞病毒保护作用的能力,并对诱导的免疫反应进行表征。用BBG2Na免疫可提高经呼吸道合胞病毒致敏小鼠的抗呼吸道合胞病毒A血清抗体滴度,诱导产生IgG1和IgG2a抗体,证明存在混合性Th反应。此外,血清阳性小鼠中诱导产生的抗G2Na抗体水平更高。最后,经呼吸道合胞病毒致敏的小鼠血清在用BBG2Na再次免疫后转移到未致敏小鼠中,其显示出比仅用呼吸道合胞病毒A免疫的小鼠血清更高的保护效力。我们的结果表明,BBG2Na具有免疫原性,并能提高经呼吸道合胞病毒致敏小鼠血清抗体的保护效力;这些结果支持了在血清阳性人群中进行临床试验的可能性。

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