Holmgren J, Svennerholm A M
J Infect Dis. 1977 Aug;136 Suppl:S105-12. doi: 10.1093/infdis/136.supplement.s105.
The adenyl cyclase-activating enterotoxin of Vibrio cholerae was shown to contain two types of subunit: six smaller units (L) that are responsible for the binding to cell membrane receptors and a larger unit (H) that mediates the toxic action. The receptor was identified as the ganglioside GM1 (galactosyl-N-acetylgalactosaminyl [sialosyl] lactosyl ceramide), and the results suggested that penetration of the toxin molecule into the membrane follows the rapid binding to GM1. The relationship of these findings to the mechanism of protective immunity, which is mediated by antibodies to the enterotoxin as well as those to the cell wall lipopolysaccharide of V. cholerae, was investigated. The antitoxic antibodies were directed mainly against the L subunit and protected by preventing binding of toxin; the antibacterial antibodies probably interfered with adhesion of V. cholerae to the intestine. The finding that the immune responses to toxin and bacteria act synergistically in protection against experimental cholera indicates that an improved cholera vaccine should contain both toxoid and lipopolysaccharide as antigens. In the rabbit, either subcutaneous or enteral immunization gave rise to intestinal synthesis of specific antibodies to V. cholerae.
六个较小的亚基（L）负责与细胞膜受体结合，一个较大的亚基（H）介导毒性作用。受体被鉴定为神经节苷脂GM1（半乳糖基-N-乙酰半乳糖胺基[唾液酸基]乳糖基神经酰胺），结果表明毒素分子在与GM1快速结合后进入细胞膜。研究了这些发现与保护性免疫机制的关系，保护性免疫由针对肠毒素以及霍乱弧菌细胞壁脂多糖的抗体介导。抗毒素抗体主要针对L亚基，通过阻止毒素结合起到保护作用；抗菌抗体可能干扰霍乱弧菌与肠道的黏附。对毒素和细菌的免疫反应在预防实验性霍乱中协同发挥作用这一发现表明，改进的霍乱疫苗应包含类毒素和脂多糖作为抗原。在兔子中，皮下或肠道免疫均可引起肠道合成针对霍乱弧菌的特异性抗体。
