Nardelli-Haefliger D, Benyacoub J, Lemoine R, Hopkins-Donaldson S, Potts A, Hartman F, Kraehenbuhl J P, De Grandi P
Department of Gynaecology, c/o Institut de Microbiologie, Bugnon 44, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland.
Vaccine. 2001 Apr 6;19(20-22):2854-61. doi: 10.1016/s0264-410x(01)00009-3.
Nasal vaccination of mice with recombinant attenuated strains of Salmonella typhimurium is more efficient at inducing antibody responses than oral vaccination. However, mortality was observed when high doses [10(9) colony forming unit (CFU)], otherwise safe by the oral route, were administered. This observation was counterbalanced by the fact that nasal vaccination was still highly efficient with lower doses (10(6) CFU), which are inefficient by the oral route and this, without any incidents of mortality. Here, we further analyse in mice the effect of nasal vaccination with differently attenuated S. typhimurium strains expressing the Hepatitis B nucleocapsid (HBc). Surprisingly, as few as 100 CFU were sufficient to induce a maximal HBc specific antibody response, but only if the bacteria were inhaled. Furthermore, we observed no correlation between the inoculum dose and the number of surviving bacteria in cervical lymph nodes and spleen. Examination of lung sections revealed strong inflammation and bronchopneumonia 24 h after nasal vaccination with 10(8) CFU, while only minor signs of inflammation were detected transiently when 10(3) CFU or phosphate buffered saline (PBS) were administered. Our data suggest that the safety issue of nasal vaccination with low doses of the Salmonella vaccine strains should be addressed in humans, as it might be an efficient alternative to oral vaccination.
用重组减毒鼠伤寒沙门氏菌菌株对小鼠进行鼻腔接种，在诱导抗体反应方面比口服接种更有效。然而，当给予高剂量[10(9)菌落形成单位（CFU）]时观察到有死亡情况，而这些剂量经口服途径是安全的。这一观察结果被以下事实所抵消：鼻腔接种低剂量（10(6)CFU）时仍然高效，而这些低剂量经口服途径则无效，并且不会出现任何死亡情况。在此，我们进一步在小鼠中分析用表达乙肝核衣壳（HBc）的不同减毒鼠伤寒沙门氏菌菌株进行鼻腔接种的效果。令人惊讶的是，低至100CFU就足以诱导最大的HBc特异性抗体反应，但前提是细菌通过吸入方式接种。此外，我们观察到接种剂量与颈部淋巴结和脾脏中存活细菌数量之间没有相关性。肺切片检查显示，用10(8)CFU进行鼻腔接种24小时后出现强烈炎症和支气管肺炎，而当给予10(3)CFU或磷酸盐缓冲盐水（PBS）时，仅短暂检测到轻微炎症迹象。我们的数据表明，低剂量沙门氏菌疫苗菌株鼻腔接种的安全性问题应在人体中加以研究，因为它可能是口服接种的一种有效替代方法。
