Fennelly G J, Khan S A, Abadi M A, Wild T F, Bloom B R
Department of Pediatrics, Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
J Immunol. 1999 Feb 1;162(3):1603-10.
An intranasal vaccine vector would elicit protective immunity at the respiratory mucosa, the portal of entry and the primary site for replication for measles virus (MV) and other respiratory viruses. In a murine model of pulmonary Shigella, we demonstrate here that a candidate-attenuated Shigella vaccine vector is safely tolerated in IFN-gamma deficient mice at an inoculum that is 1 million-fold higher than the inoculum of the wild-type parent strain that would be lethal for greater than 90% of these mice. Also, following intranasal inoculation, the Deltaasd Shigella harboring a DNA MV vaccine plasmid induces a vigorous MV-specific Th1-type (both CD8+ CTL and IFN-gamma) and, to a lesser degree, Th2-type responses among splenocytes in addition to low levels of IgG and IgA in the serum. Priming for MV-specific CTL responses was possible in mice that had prior infection with a wild-type Shigella of the same serotype. Remarkably, mice immunized by the intranasal route with attenuated Shigella harboring the DNA MV vaccine plasmid had a level of MV-specific CTL activity among splenocytes that was comparable with levels observed in mice immunized by the i.p. route with attenuated Salmonella typhi harboring the same DNA vaccine plasmid, despite the fact that Shigella remained localized to the lungs, yet Salmonella disseminated to the spleen following inoculation. Thus, Deltaasd Shigella represents a very useful vector for delivery of DNA vaccines to mucosal lymphoid tissues.
鼻内疫苗载体可在呼吸道黏膜引发保护性免疫，呼吸道黏膜是麻疹病毒（MV）及其他呼吸道病毒的侵入门户和主要复制部位。在肺部志贺氏菌的小鼠模型中，我们在此证明，一种候选减毒志贺氏菌疫苗载体在干扰素-γ缺陷小鼠中能安全耐受，其接种量比野生型亲本菌株的接种量高100万倍，而野生型亲本菌株的接种量会导致超过90%的此类小鼠死亡。此外，鼻内接种后，携带DNA MV疫苗质粒的缺失asd基因的志贺氏菌除了在血清中诱导产生低水平的IgG和IgA外，还能在脾细胞中诱导强烈的MV特异性Th1型（CD8+CTL和干扰素-γ）反应，并在较小程度上诱导Th2型反应。对于先前感染过相同血清型野生型志贺氏菌的小鼠，引发MV特异性CTL反应是可能的。值得注意的是，经鼻内途径用携带DNA MV疫苗质粒的减毒志贺氏菌免疫的小鼠，其脾细胞中的MV特异性CTL活性水平与经腹腔途径用携带相同DNA疫苗质粒的减毒伤寒沙门氏菌免疫的小鼠所观察到的水平相当，尽管志贺氏菌仍局限于肺部，而沙门氏菌接种后会扩散到脾脏。因此，缺失asd基因的志贺氏菌是将DNA疫苗递送至黏膜淋巴组织的一种非常有用的载体。
