Donnelly J J, Deck R R, Liu M A
Department of Cancer Research, Merck Sharp & Dohme Research Laboratories, West Point PA 19486.
J Immunol. 1990 Nov 1;145(9):3071-9.
Polysaccharide-protein conjugate vaccines made with different carriers vary in their ability to elicit antipolysaccharide IgG antibody responses in young infants and an adult mouse model, suggesting that the carrier proteins used in the conjugate vaccines differ in their ability to act as carriers, or that additional mechanisms of immunogenicity play a role. A conjugate vaccine of Haemophilus influenzae PRP coupled to the outer membrane protein complex (OMPC) of Neisseria meningitidis serogroup B is immunogenic in children as young as 2 mo of age and is immunogenic in infant rhesus monkeys, an animal model for infant humans. In the present study, PRP-OMPC was found to induce efficient IgM to IgG switching of anti-PRP serum antibody in adult mice, whereas PRP conjugated to two other protein carriers did not. Thus the PRP-OMPC conjugate was examined in order to determine why PRP coupled to OMPC was so immunogenic, even more immunogenic than conjugates made with other carrier proteins. The OMPC carrier differs from the other protein carriers in that the proteins are present in a liposomal form containing lipids (including LPS) derived from the outer membrane of N. meningitidis. We studied the OMPC to see whether the different components or the nature of the OMPC carrier could contribute to its enhanced immunogenicity. Specifically we evaluated the OMPC for both classic Th cell carrier activity and adjuvanticity, and the LPS component of OMPC for systemic polyclonal B cell activation. Carrier recognition of the OMPC moiety of PRP-OMPC was demonstrated. In addition the PRP-OMPC conjugate vaccine was observed to have adjuvant properties for both T cell-dependent and T cell-independent Ag in the absence of LPS-induced systemic polyclonal B cell activation. These observations suggest that in addition to functioning as a classic protein carrier whereby the proteins in OMPC provide Th cell epitopes, the OMPC also has adjuvant activity that distinguishes it from other protein carriers and may contribute to the increased immunogenicity of PRP-OMPC conjugates in animal models.
用不同载体制成的多糖-蛋白结合疫苗在引发幼儿和成年小鼠模型中抗多糖IgG抗体反应的能力上存在差异，这表明结合疫苗中使用的载体蛋白在作为载体的能力上有所不同，或者免疫原性的其他机制发挥了作用。一种将b型流感嗜血杆菌PRP与B群脑膜炎奈瑟菌外膜蛋白复合物（OMPC）偶联的结合疫苗在2个月大的儿童中具有免疫原性，在幼年恒河猴（人类婴儿的动物模型）中也具有免疫原性。在本研究中，发现PRP-OMPC能在成年小鼠中诱导抗PRP血清抗体从IgM高效转换为IgG，而与其他两种蛋白载体偶联的PRP则不能。因此，对PRP-OMPC结合物进行了研究，以确定为什么与OMPC偶联的PRP具有如此强的免疫原性，甚至比用其他载体蛋白制成的结合物免疫原性更强。OMPC载体与其他蛋白载体的不同之处在于，这些蛋白以脂质体形式存在，其中含有源自脑膜炎奈瑟菌外膜的脂质（包括LPS）。我们研究了OMPC，看其不同成分或载体性质是否有助于增强其免疫原性。具体而言，我们评估了OMPC的经典Th细胞载体活性和佐剂活性，以及OMPC的LPS成分对全身性多克隆B细胞的激活作用。证实了对PRP-OMPC的OMPC部分的载体识别。此外，观察到PRP-OMPC结合疫苗在不存在LPS诱导的全身性多克隆B细胞激活的情况下，对T细胞依赖性和T细胞非依赖性抗原均具有佐剂特性。这些观察结果表明，除了作为经典的蛋白载体发挥作用（OMPC中的蛋白提供Th细胞表位）外，OMPC还具有佐剂活性，这使其有别于其他蛋白载体，并可能有助于增强PRP-OMPC结合物在动物模型中的免疫原性。
