Del Giudice G
World Health Organisation-Immunology Research and Training Centre, Department of Pathology, University of Geneva, Switzerland.
Experientia. 1994 Nov 30;50(11-12):1061-6. doi: 10.1007/BF01923462.
One problem associated with the development of subunit vaccines is their limited immunogenicity, due to their physico-chemical structure, their inability to encounter the correct MHC restriction element, or the need for strong adjuvants to be delivered along with them. These problems are usually solved by conjugating target epitopes (peptides or oligosaccharides) with carrier proteins which provide a source of T-cell epitopes recognised by a large proportion of the vaccinated individuals. We have shown that mycobacterial hsp65 and hsp70 exert a strong helper effect in vivo when conjugated to synthetic peptides or oligosaccharides. Interestingly, this helper effect did not require the need for any adjuvant, either in mice or in monkeys. The helper effect mediated by the hsp65 required that animals were previously primed with either live BCG or the hsp65 alone; on the other hand, such a priming was not required when the hsp70 was used in the conjugates. Similar results were obtained with HSP molecules from Escherichia coli. This may suggest that the adjuvant-free helper effect observed applies not only to mycobacterial HSP, but also to HSP from other prokaryotes. These findings suggest that microbial hsp70 could be considered for the design of conjugated vaccine constructs for eventual human use.
与亚单位疫苗开发相关的一个问题是其免疫原性有限，这归因于它们的物理化学结构、无法遇到正确的MHC限制元件，或者需要与它们一起递送强佐剂。这些问题通常通过将靶表位（肽或寡糖）与载体蛋白偶联来解决，载体蛋白提供了被大部分接种个体识别的T细胞表位来源。我们已经表明，分枝杆菌hsp65和hsp70与合成肽或寡糖偶联时在体内发挥强大的辅助作用。有趣的是，无论是在小鼠还是在猴子中，这种辅助作用都不需要任何佐剂。hsp65介导的辅助作用要求动物预先用活卡介苗或单独的hsp65进行致敏；另一方面，当在偶联物中使用hsp70时则不需要这种致敏。来自大肠杆菌的HSP分子也获得了类似结果。这可能表明观察到的无佐剂辅助作用不仅适用于分枝杆菌HSP，也适用于来自其他原核生物的HSP。这些发现表明，微生物hsp70可考虑用于设计最终供人类使用的偶联疫苗构建体。
