Nakouzi Antonio, Zhang Tong, Oscarson Stefan, Casadevall Arturo
Department of Microbiology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Vaccine. 2009 Jun 2;27(27):3513-8. doi: 10.1016/j.vaccine.2009.03.089. Epub 2009 Apr 19.
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.
新型隐球菌荚膜葡糖醛酸木聚糖甘露聚糖（GXM）是一种潜在的疫苗抗原，可引发保护性和非保护性抗体。为了将免疫反应集中在单一抗原成分上，合成了一种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。用M2-HSA免疫的小鼠产生的单克隆抗体（mAb）呈现出与非保护性mAb相关的特征性点状免疫荧光。M2免疫引发的mAb均无调理作用。被动给予M2-HSA引发的mAb没有保护作用，用M2-HSA和HSA免疫的小鼠存活率没有差异。因此，我们得出结论，M2基序代表新型隐球菌GXM中的一个抗原决定簇，可引发非保护性反应，不是合适的疫苗候选物。此外，这些结果首次对新型隐球菌多糖表位进行了分子定位，并提出了鉴定GXM表位的一般策略。
