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The common Cryptococcus neoformans glucuronoxylomannan M2 motif elicits non-protective antibodies

机译：常见的新型隐球菌葡糖醛酸甘露聚糖M2基序引发非保护性抗体

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摘要

The Cryptococcus neoformans capsular glucuronoxylomannan (GXM) is a potential vaccine antigen that can elicit protective and non-protective antibodies. In an attempt to focus the immune response on a single antigenic component, a heptasaccharide oligosaccharide representing the major structural motif (M2) of the most common clinical isolate was synthesized and conjugated to human serum albumin (HSA). Monoclonal antibodies (mAbs) generated from mice immunized with M2-HSA produced the characteristic punctuate immunofluorescence associated with non-protective mAbs. None of the mAbs elicited by M2 immunization was opsonic. Passive administration of mAbs elicited by M2-HSA was not protective and there was no difference in the survival of mice immunized with M2-HSA and HSA. Hence, we conclude that the M2 motif represents an antigenic determinant in C. neoformans GXM that elicits non-protective responses and is not a suitable vaccine candidate. Furthermore, the results illustrate the first molecular assignment of a C. neoformans polysaccharide epitope and suggest a general strategy for the identification of GXM epitopes.
机译：新型隐球菌荚膜葡糖醛酸羟甘露聚糖（GXM）是一种潜在的疫苗抗原，可引起保护性和非保护性抗体。为了将免疫应答集中在单个抗原成分上，合成了代表最常见临床分离株主要结构基序（M2）的七糖寡糖，并将其与人血清白蛋白（HSA）偶联。从用M2-HSA免疫的小鼠中产生的单克隆抗体（mAb）产生了与非保护性mAb相关的特征性标点免疫荧光。 M2免疫引发的单克隆抗体都不是调理的。由M2-HSA引发的mAb的被动给药没有保护性，并且用M2-HSA和HSA免疫的小鼠的存活率没有差异。因此，我们得出的结论是，M2基序代表新孢子虫GXM中的抗原决定簇，该抗原决定簇引发非保护性应答，因此不是合适的疫苗候选物。此外，结果说明了新孢梭菌多糖表位的第一个分子分配，并提出了鉴定GXM表位的一般策略。

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