Proteoliposome and Polysaccharide-Based Meningococcal Vaccine Are Immunogenic in Infants and Toddlers and Primes for Memory against Serogroup C Polysaccharide

O. Pérez, B. Romeu, J. Campo, C. Zayas, M. Lastre
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引用次数: 4

Abstract

Neisseria meningitidis capsular polysaccharides are the main target of the protective immune response against bacterial meningitis. They are thymus-independent type 2 (TI-2) antigens that are poorly immunogenic and not protective in young children, and their administration may impair subsequent challenge with the same polysaccharide. These problems have been addressed using three different vaccines consisting of 1) polysaccharide alone, 2) polysaccharide covalently conjugated to a carrier protein, and 3) polysaccharide with Proteoliposome (PL) adsorbed onto Al(OH)3. VA-MENGOC-BC ® is one of the third types of vaccine. It contains PL (detergent-extracted external membrane proteins forming vesicles) and polysaccharide (Ps) from N. meningitidis serogroups B and C (PsC), respectively. Nevertheless, there is a concern that to overcome the TI-2 nature of Ps the covalently conjugation to a carrier is mandatory. Therefore, we evaluated the immune response induced by VA-MENGOC-BC ® in infants and toddlers in order to determine whether it stimulates the response against the PsC. High IgG anti PsC and anti PL responses were seen following the administration of two doses in infants and toddlers, after a 3 rd dose in pre-teenagers, and after confirmed carrier stages in young adults. The anti PL IgG response persisted longer than anti PsC IgG response and IgM response against both antigens was maintained. An IgG1 anti PL response predominated, as well as IgG4 > IgG3 > IgG1 anti PsC responses. These results suggest that non-covalent incorporation of PsC onto Al(OH)3 containing PL as adjuvant is immunogenic, primes for memory, and induces long-lasting specific antibody response. The improved PsC immunogenicity of this vaccine may be due to the preferential and potent Th1 response induced in mice and human by the PL as adjuvant.
蛋白脂质体和基于多糖的脑膜炎球菌疫苗在婴幼儿中具有免疫原性,并对血清C群多糖有记忆作用
荚膜脑膜炎奈瑟菌多糖是针对细菌性脑膜炎的保护性免疫反应的主要目标。它们是胸腺不依赖的2型(TI-2)抗原,免疫原性差,对幼儿没有保护作用,并且它们的施用可能会损害随后使用相同多糖的攻击。这些问题已经通过三种不同的疫苗得到解决:1)单独的多糖,2)与载体蛋白共价结合的多糖,以及3)与蛋白脂质体(PL)吸附在Al(OH)3上的多糖。VA-MENGOC-BC®是第三种疫苗之一。它含有分别来自脑膜炎奈瑟菌血清群B和C (PsC)的PL(洗涤剂提取的外膜蛋白形成囊泡)和多糖(Ps)。然而,有一种担忧是,为了克服Ps的TI-2性质,与载体的共价共轭是强制性的。因此,我们评估了VA-MENGOC-BC®在婴幼儿中诱导的免疫应答,以确定它是否刺激了针对PsC的应答。高IgG抗PsC和抗PL反应在婴儿和学步儿童服用两剂后,在青少年前服用第三剂后,在年轻人确认携带者阶段后被观察到。抗PL IgG应答持续时间长于抗PsC IgG应答,且对两种抗原均维持IgM应答。IgG1抗PL应答以及IgG4 > IgG3 > IgG1抗PsC应答占主导地位。这些结果表明,将PsC非共价结合到含有PL作为佐剂的Al(OH)3上具有免疫原性,启动记忆,并诱导持久的特异性抗体反应。该疫苗的PsC免疫原性的提高可能是由于PL作为佐剂在小鼠和人体内诱导的优先和有效的Th1反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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