Immunization of humans with recombinant pneumococcal surface protein A (rPspA) elicits antibodies that passively protect mice from fatal infection with Streptococcus pneumoniae bearing heterologous PspA
Immunization of humans with recombinant pneumococcal surface protein A (rPspA) elicits antibodies that passively protect mice from fatal infection with Streptococcus pneumoniae bearing heterologous PspA
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DOI：
10.1086/317602
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发表时间：
2000-12-01
影响因子：
6.4
通讯作者：
Nabors, GS
中科院分区：
文献类型：
--
作者：
Briles, DE;Hollingshead, SK;Nabors, GS
肺炎球菌表面蛋白A（PspA）是一种由所有肺炎球菌表达的交叉反应蛋白，已知其在动物中引发抗体，该抗体可以被动地保护小鼠免受肺炎链球菌感染。重组PspA的I期试验显示该蛋白在人类中具有免疫原性。对来自本试验的免疫前和免疫后血清样品进行了检查，并且抗PspA的人抗体可以保护小鼠免受肺炎球菌感染。用125 μ g PspA免疫两次的受试者的血清样品具有>100倍于持续保护小鼠免受致命感染所需的抗体/毫升（1.3 μ g/剂量）。至少98%的PspA属于PspA序列/血清学家族1或2。由家族1 PspA引发的人抗体保护免受S.用表达家族1或2的PspA的肺炎链球菌菌株和所有3种测试的荚膜类型的菌株：3、6A和6 B。这些研究表明PspA可能具有作为人类疫苗的功效。
Pneumococcal surface protein A (PspA), a cross-reactive protein expressed by all pneumococci, is known to elicit an antibody in animals that can passively protect mice from infection with Streptococcus pneumoniae. A phase I trial with recombinant PspA showed the protein to be immunogenic in humans. Pre- and postimmune serum samples from this trial were examined, and human antibody to PspA could protect mice from pneumococcal infection. The serum samples of subjects immunized twice with 125 mug of PspA had >100 times as much antibody per milliliter as was required to consistently protect mice from fatal infection (1.3 mug/dose). At least 98% of PspAs fall into PspA sequence/serologic families 1 or 2. Human antibodies elicited by a family 1 PspA protected against infection with S. pneumoniae expressing either family 1 or 2 PspAs and with strains of all 3 capsular types tested: 3, 6A, and 6B. These studies suggest that PspA may have efficacy as a human vaccine.