Tamura S, Asanuma H, Tomita T, Komase K, Kawahara K, Danbara H, Hattori N, Watanabe K, Suzuki Y, Nagamine T
Department of Pathology, National Institute of Health, Tokyo, Japan.
Vaccine. 1994 Sep;12(12):1083-9. doi: 10.1016/0264-410x(94)90177-5.
Escherichia coli heat-labile enterotoxin B subunit (LTB) (2 micrograms), supplemented with a trace amount of the holotoxin (LT) (0.02-20 ng), was examined for the adjuvant effect on antibody (Ab) responses against influenza inactivated haemagglutinin (HA) vaccine in Balb/c mice. Each mouse received a primary intranasal (i.n.) inoculation with the vaccine (1.5 micrograms), prepared from PR8 (H1N1) virus, together with LT-containing LTB and in 4 weeks a second i.n. inoculation of the vaccine alone. The inoculation of the vaccine with the LT-containing LTB induced significantly high primary and secondary anti-HA IgA and IgG Ab responses in the nasal wash and the serum, while the vaccine with LTB or less than 2 ng of LT induced little response. The synergistic adjuvant effect was maximal in the concentration of LTB supplemented with 0.2-2 ng of LT. Under these conditions, the augmented IgA and IgG Ab responses, which are cross-protective to PR8 HA molecules, provided complete cross-protection against PR8 virus challenge in mice immunized with heterologous vaccine within the same subtype. These results suggest that LTB containing a trace amount of LT can be used as a potent adjuvant for nasal vaccination of humans against influenza.
研究了补充微量全毒素（LT）（0.02 - 20纳克）的大肠杆菌不耐热肠毒素B亚基（LTB）（2微克）对Balb/c小鼠针对流感灭活血凝素（HA）疫苗的抗体（Ab）反应的佐剂作用。每只小鼠经鼻内（i.n.）初次接种由PR8（H1N1）病毒制备的疫苗（1.5微克），同时接种含LT的LTB，4周后再次经鼻内单独接种该疫苗。接种含LT的LTB的疫苗在鼻洗液和血清中诱导出显著更高的初次和二次抗HA IgA和IgG抗体反应，而接种含LTB或少于2纳克LT的疫苗诱导的反应很小。在补充0.2 - 2纳克LT的LTB浓度下，协同佐剂效应最大。在这些条件下，增强的IgA和IgG抗体反应对PR8 HA分子具有交叉保护作用，为同一亚型内用异源疫苗免疫的小鼠提供了针对PR8病毒攻击的完全交叉保护。这些结果表明，含有微量LT的LTB可作为人类流感鼻内疫苗接种的有效佐剂。
