Dale J B, Simmons M, Chiang E C, Chiang E Y
VA Medical Center (11A), Memphis, TN 38104, USA.
Vaccine. 1996 Jul;14(10):944-8. doi: 10.1016/0264-410x(96)00050-3.
One of the major obstacles to the development of group A streptococcal M protein vaccines is the multiplicity of M serotypes expressed by these organisms. In this study, we have constructed a recombinant, hybrid M protein that contains type-specific aminoterminal fragments of eight different M proteins. We show that the purified hybrid recombinant protein is immunogenic in rabbits and evokes antibodies that react with native M proteins from the respective streptococcal serotypes. In addition, the immune sera evoked by the octavalent protein opsonized six of the eight serotypes of streptococci, indicating that the majority of the M protein fragments contained protective epitopes that retained their native conformations in the hybrid protein. None of the antisera raised against the octavalent protein crossreacted with human heart tissue. These studies indicate that multivalent, hybrid M proteins may be used to elicit broadly protective immune responses against multiple serotypes of group A streptococci.
A群链球菌M蛋白疫苗研发的主要障碍之一是这些细菌所表达的M血清型的多样性。在本研究中，我们构建了一种重组杂交M蛋白，它包含8种不同M蛋白的型特异性氨基末端片段。我们发现，纯化后的杂交重组蛋白在兔体内具有免疫原性，并能诱导产生与相应链球菌血清型的天然M蛋白发生反应的抗体。此外，由八价蛋白诱导产生的免疫血清能调理八种链球菌血清型中的六种，这表明大多数M蛋白片段包含保护性表位，且这些表位在杂交蛋白中保留了其天然构象。针对八价蛋白产生的抗血清均未与人心脏组织发生交叉反应。这些研究表明，多价杂交M蛋白可用于引发针对多种A群链球菌血清型的广泛保护性免疫反应。
