Frantz J C, Bhatnagar P K, Brown A L, Garrett L K, Hughes J L
Infect Immun. 1987 May;55(5):1077-84. doi: 10.1128/iai.55.5.1077-1084.1987.
In its native form Escherichia coli heat-stable enterotoxin (STa) is nonantigenic; however, neutralizing antibodies are elicited in animals vaccinated with toxin-carrier conjugates. To study the immunogenicity of STa, peptides STa1-18 and STa5-18 were synthesized, characterized, and conjugated to carrier proteins. Pregnant gilts and heifers were hyperimmunized with the respective conjugates. Following parturition neonates were challenged with virulent E. coli (K99+ STa+). Peptides coupled to ovalbumin and emulsified with Freund adjuvant elicited antibodies that neutralized toxin-induced fluid accumulation in suckling mice. Peptides coupled to particulate carriers, with or without muramyl dipeptide adjuvant, failed to induce a measurable response. Peak antibody levels in sera were observed following three doses of conjugate and persisted for several weeks. The serological response in cattle was superior to that observed in swine; however, antibody levels in porcine colostrum were higher than those observed in cattle. Clinical observations of neonates from vaccinated dams indicated that passively obtained antibody provided partial protection from disease, but not as complete as that demonstrable with whole cell bacterins that induce antibody to pili. However, the data suggest the potential for utility of synthetically prepared antigens.
天然形式的大肠杆菌热稳定肠毒素(STa)无抗原性;然而,在用毒素-载体偶联物免疫的动物中可诱导产生中和抗体。为了研究STa的免疫原性,合成、表征了肽段STa1-18和STa5-18,并将其与载体蛋白偶联。用各自的偶联物对怀孕的后备母猪和小母牛进行超免疫。分娩后,用强毒大肠杆菌(K99+ STa+)攻击新生仔猪。与卵清蛋白偶联并用弗氏佐剂乳化的肽段可诱导产生抗体,这些抗体能中和毒素诱导的哺乳小鼠体液积聚。与颗粒载体偶联的肽段,无论有无胞壁酰二肽佐剂,均未能诱导出可测量的反应。在给予三剂偶联物后观察到血清中抗体水平达到峰值,并持续数周。牛的血清学反应优于猪;然而,猪初乳中的抗体水平高于牛。对来自接种疫苗母猪的新生仔猪的临床观察表明,被动获得的抗体可提供部分疾病保护,但不如诱导产生菌毛抗体的全细胞菌苗所提供的保护完全。然而,数据表明合成制备的抗原有潜在用途。