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Safety, immunogenicity, and efficacy against cholera challenge in humans of a typhoid-cholera hybrid vaccine derived from Salmonella typhi Ty21a.

机译:源自伤寒沙门氏菌Ty21a的伤寒-霍乱混合疫苗在人中对抗霍乱的安全性,免疫原性和功效。

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A live oral vaccine consisting of attenuated Salmonella typhi Ty21a expressing Vibrio cholerae O1 Inaba lipopolysaccharide (LPS) O antigen was constructed and tested in volunteers for safety, immunogenicity, and efficacy. Fourteen adults ingested three doses of 10(10) viable organisms with buffer. One month later, 8 vaccinees and 13 unimmunized controls were challenged with 10(6) pathogenic V. cholerae O1 E1 T or Inaba organisms. No significant adverse reactions to vaccination were observed. All volunteers had significant rises in serum immunoglobulin G (IgG) antibody to S. typhi LPS. Only 2 (14%) of 14 had significant rises in serum IgA or IgG antibody to Inaba LPS, and 5 (36%) of 14 had fourfold rises in vibriocidal antibody. In the challenge study, diarrhea occurred in 13 of 13 controls and 6 of 8 vaccinees (vaccine efficacy, 25%; P = 0.13). The vaccine significantly reduced the severity of the clinical illness (P less than 0.05) and caused decreased excretion of challenge vibrios (P less than 0.05). Although the typhoid-cholera hybrid vaccine did not provide significant protection overall against experimental cholera, this study demonstrates the importance of antibody to V. cholerae O antigen in ameliorating clinical illness and illustrates the use of an S. typhi carrier vaccine strain expressing a foreign antigen.
机译:构建了由表达霍乱弧菌O1稻叶脂多糖(LPS)O抗原的减毒伤寒沙门氏菌Ty21a组成的活口服疫苗,并在志愿者中进行了安全性,免疫原性和功效测试。十四名成年人摄入了三剂含缓冲液的10(10)活菌。一个月后,用10(6)个致病性霍乱弧菌O1 E1 T或Inaba生物攻击8种疫苗和13个未免疫对照。没有观察到明显的疫苗不良反应。所有志愿者的伤寒沙门氏菌LPS血清免疫球蛋白G(IgG)抗体均显着升高。 14人中只有2人(14%)的针对Inaba LPS的血清IgA或IgG抗体明显升高,而14人中有5人(36%)的杀弧菌抗体升高了四倍。在攻击研究中,腹泻发生在13名对照中的13名和8种疫苗中的6种(疫苗效力,25%; P = 0.13)。该疫苗显着降低了临床疾病的严重程度(P小于0.05),并导致挑战性弧菌排泄减少(P小于0.05)。尽管伤寒霍乱混合疫苗并未提供针对实验霍乱的全面保护,但这项研究表明霍乱弧菌O抗原抗体在改善临床疾病中的重要性,并阐明了表达外源抗原的伤寒沙门氏菌载体疫苗株的用途。

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