Hu Mary C, Walls Michael A, Stroop Steven D, Reddish Mark A, Beall Bernard, Dale James B
ID Biomedical Corporation, Bothell, Washington, USA.
Infect Immun. 2002 Apr;70(4):2171-7. doi: 10.1128/IAI.70.4.2171-2177.2002.
A multivalent vaccine containing amino-terminal M protein fragments from 26 different serotypes of group A streptococci was constructed by recombinant techniques. The vaccine consisted of four different recombinant proteins that were formulated with alum to contain 400 microg of protein per dose. Rabbits were immunized via the intramuscular route at 0, 4, and 16 weeks. Immune sera were assayed for the presence of type-specific antibodies against the individual recombinant M peptides by enzyme-linked immunosorbent assay and for opsonic antibodies by in vitro opsonization tests and indirect bactericidal tests. The 26-valent vaccine was highly immunogenic and elicited fourfold or greater increases in antibody levels against 25 of the 26 serotypes represented in the vaccine. The immune sera were broadly opsonic and were bactericidal against the majority of the 26 different serotypes. Importantly, none of the immune sera cross-reacted with human tissues. Our results indicate that type-specific, protective M protein epitopes can be incorporated into complex, multivalent vaccines designed to elicit broadly protective opsonic antibodies in the absence of tissue-cross-reactive antibodies.
通过重组技术构建了一种包含来自26种不同血清型A组链球菌氨基末端M蛋白片段的多价疫苗。该疫苗由四种不同的重组蛋白组成，与明矾配制成每剂含400微克蛋白质。在第0、4和16周通过肌肉注射途径对兔子进行免疫。通过酶联免疫吸附测定法检测免疫血清中针对各个重组M肽的型特异性抗体的存在，并通过体外调理试验和间接杀菌试验检测调理抗体。这种26价疫苗具有高度免疫原性，可使疫苗中所代表的26种血清型中的25种血清型的抗体水平提高四倍或更多。免疫血清具有广泛的调理作用，并且对26种不同血清型中的大多数具有杀菌作用。重要的是，没有一种免疫血清与人体组织发生交叉反应。我们的结果表明，型特异性保护性M蛋白表位可以被纳入复杂的多价疫苗中，该疫苗旨在在不存在组织交叉反应性抗体的情况下引发广泛保护性调理抗体。
