Akhiani A A, Stensson A, Schön K, Lycke N
Department of Clinical Immunology, Göteborg University, Göteborg, Sweden.
Scand J Immunol. 2006 Feb;63(2):97-105. doi: 10.1111/j.1365-3083.2005.01713.x.
Safe and efficacious adjuvants are much needed to facilitate the development of mucosal vaccines. Here, we have asked whether our nontoxic vaccine adjuvant, CTA1-DD, can enhance protective immunity against Helicobacter pylori infection. Intranasal immunizations with H. pylori lysate together with CTA1-DD-adjuvant induced significant protection in C57Bl/6 mice, almost as strong as similar immunizations using cholera toxin (CT)-adjuvant. Protection remained strong even at 8 weeks postchallenge and the bacterial colonization was reduced by 20-fold compared to lysate-immunized controls. Although CTA1-DD was designed to bind to B cells, microMT mice developed significant, but lower, level of protection following immunization. Intranasal immunizations with CT adjuvant in C57Bl/6 mice resulted in the development of severe postimmunization gastritis at 2 and 8 weeks postchallenge, whereas the degree of gastritis was substantially lower in the CTA1-DD-immunized mice. Protection induced by both CTA1-DD- and CT adjuvant was associated with a strong local infiltration of CD4(+) T cells in the gastric mucosa, and recall responses to specific Ag elicited substantial IFN-gamma production, indicating Th1-dominance. These findings clearly demonstrate that CTA1-DD adjuvant is a promising candidate to be further exploited in the development of a mucosal vaccine against H. pylori infection.
非常需要安全有效的佐剂来促进黏膜疫苗的研发。在此，我们探讨了我们的无毒疫苗佐剂CTA1-DD是否能增强针对幽门螺杆菌感染的保护性免疫。用幽门螺杆菌裂解物与CTA1-DD佐剂进行鼻内免疫，在C57Bl/6小鼠中诱导出显著的保护作用，几乎与使用霍乱毒素（CT）佐剂的类似免疫一样强。即使在攻毒后8周，保护作用仍然很强，与裂解物免疫的对照组相比，细菌定植减少了20倍。尽管CTA1-DD被设计用于结合B细胞，但microMT小鼠在免疫后产生了显著但较低水平的保护作用。在C57Bl/6小鼠中用CT佐剂进行鼻内免疫，在攻毒后2周和8周导致严重的免疫后胃炎，而在CTA1-DD免疫的小鼠中胃炎程度明显较低。CTA1-DD和CT佐剂诱导的保护作用都与胃黏膜中CD4(+) T细胞的强烈局部浸润有关，对特定抗原的回忆反应引发大量IFN-γ产生，表明以Th1为主导。这些发现清楚地表明，CTA1-DD佐剂是一种有前途的候选物，可在开发抗幽门螺杆菌感染的黏膜疫苗中进一步加以利用。
