Brossier Fabien, Levy Martine, Mock Michèle
Unité des Toxines et Pathogénie Bactérienne (CNRS URA 2172), Institut Pasteur, 75725 Paris Cedex 15, France.
Infect Immun. 2002 Feb;70(2):661-4. doi: 10.1128/IAI.70.2.661-664.2002.
Anthrax is caused by Bacillus anthracis, a gram-positive spore-forming bacterium. Septicemia and toxemia rapidly lead to death in infected mammal hosts. Currently used acellular vaccines against anthrax consist of protective antigen (PA), one of the anthrax toxin components. However, in experimental animals such vaccines are less protective than live attenuated strains. Here we demonstrate that the addition of formaldehyde-inactivated spores (FIS) of B. anthracis to PA elicits total protection against challenge with virulent B. anthracis strains in mice and guinea pigs. The toxin-neutralizing activities of sera from mice immunized with PA alone or PA plus FIS were similar, suggesting that the protection conferred by PA plus FIS was not only a consequence of the humoral response to PA. A PA-deficient challenge strain was constructed, and its virulence was due solely to its multiplication. Immunization with FIS alone was sufficient to protect mice partially, and guinea pigs totally, against infection with this strain. This suggests that spore antigens contribute to protection. Guinea pigs and mice had very different susceptibilities to infection with the nontoxigenic strain, highlighting the importance of verifying the pertinence of animal models for evaluating anthrax vaccines.
炭疽病由炭疽芽孢杆菌引起，这是一种革兰氏阳性的产芽孢细菌。败血症和毒血症会迅速导致受感染的哺乳动物宿主死亡。目前使用的抗炭疽无细胞疫苗由保护性抗原（PA）组成，它是炭疽毒素的成分之一。然而，在实验动物中，此类疫苗的保护作用不如减毒活菌株。在此我们证明，将炭疽芽孢杆菌的甲醛灭活孢子（FIS）添加到PA中，可使小鼠和豚鼠对强毒炭疽芽孢杆菌菌株的攻击产生完全保护。单独用PA或PA加FIS免疫的小鼠血清的毒素中和活性相似，这表明PA加FIS所提供的保护不仅是对PA体液反应的结果。构建了一株缺乏PA的攻击菌株，其毒力仅归因于其繁殖。单独用FIS免疫足以部分保护小鼠，并完全保护豚鼠免受该菌株的感染。这表明孢子抗原有助于提供保护。豚鼠和小鼠对无毒菌株感染的易感性差异很大，这突出了验证动物模型对评估炭疽疫苗相关性的重要性。
