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首页> 外文期刊>Infection and immunity >Synthesis, characterization, and immunologic properties of detoxified lipooligosaccharide from nontypeable Haemophilus influenzae conjugated to proteins.
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Synthesis, characterization, and immunologic properties of detoxified lipooligosaccharide from nontypeable Haemophilus influenzae conjugated to proteins.

机译：从蛋白质缀合的无卵泡血液嗜酚菌的疏散脂质糖的合成，表征和免疫学特性。

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Nontypeable Haemophilus influenzae (NTHi) is an important cause of otitis media in children and of pneumonitis in adults with depressed resistance. Lipooligosaccharide (LOS) is a major surface antigen of NTHi and elicits bactericidal and opsonic antibodies. We prepared detoxified LOS (dLOS) protein conjugates from NTHi for use as experimental vaccines. LOS from NTHi 9274 was treated with anhydrous hydrazine and had its toxicity reduced to clinically acceptable levels. dLOS was bound to tetanus toxoid (TT) or high- molecular-weight proteins (HMPs) from NTHi through a linker of adipic acid dihydrazide to form dLOS-TT or dLOS-HMP. The molar ratio of the dLOS to protein carriers ranged from 26:1 to 50:1. The antigenicity of the conjugates was similar to that of the LOS alone as determined by double immunodiffusion. Subcutaneous or intramuscular injection of the conjugates elicited a 28- to 486-fold rise in the level of immunoglobulin G antibodies in mice to the homologous LOS after two or three injections and a 169- to 243-fold rise in the level of immunoglobulin G antibodies in rabbits after two injections. The immunogenicity of the conjugates in mice and rabbits was enhanced by formulation with monophosphoryl lipid A plus trehalose dimycolate. In rabbits, conjugate-induced LOS antibodies induced complement-mediated bactericidal activity against the homologous strain 9274 and prototype strain 3189. These results indicate that a detoxified LOS-protein conjugate is a candidate vaccine for otitis media and pneumonitis caused by NTHi.
机译：嗜血杆菌（Nthi）是儿童中耳炎和肺炎的肺炎患者患者抑郁症的重要原因。脂肪寡糖（LOS）是NTHI的主要表面抗原，并引发杀菌和OPSONIC抗体。我们制备了从NTHI中制备的解毒LOS（DLOS）蛋白缀合物用作实验疫苗。 NTHI 9274的LOS用无水肼处理，毒性降低到临床上可接受的水平。通过通过己二酸二酰肼的接头，将DLOS与NTHI通过NHI的Tetanus毒素（TT）或高分子量蛋白（HMP）结合，形成DLOS-TT或DLOS-HMP。 DLO与蛋白质载体的摩尔比范围为26：1至50：1。缀合物的抗原性与单独的单独的单独的抗原性相似。皮下或肌内注射缀合物在两次或三次注射后，在小鼠中的免疫球蛋白G抗体的水平中引起了28-至486倍的升高，并在免疫球蛋白G抗体水平中升高了169-243倍在两次注射后的兔子。通过用单磷虾脂质A加海藻糖二氯化物的配制增强了小鼠和兔中的缀合物和兔子的免疫原性。在兔中，缀合物诱导的LOS抗体诱导与同源菌株9274和原型菌株3189的互补介导的杀菌活性。这些结果表明，解毒的LOS-蛋白缀合物是用于中耳炎的候选疫苗和由NTHI引起的肺炎。

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