Rothel J S, Waterkeyn J G, Strugnell R A, Wood P R, Seow H F, Vadolas J, Lightowlers M W
University of Melbourne, Molecular Parasitology Laboratory, Veterinary Clinical Centre, Werribee, Australia.
Immunol Cell Biol. 1997 Feb;75(1):41-6. doi: 10.1038/icb.1997.7.
This report describes the use of a nucleic acid vaccine in a large outbred animal species both alone and in combination with a conventionally adjuvanted vaccine. The gene encoding a host-protective antigen (45W) from the sheep parasite Taenia ovis was cloned into the expression vector pcDNA3 and the resultant plasmid termed pcDNA3-45W. Eleven of 15 sheep injected either intramuscularly or intradermally with pcDNA3-45W mounted a serum antibody response to 45W which for both routes of injection was predominantly IgG1. However, the level of antibody elicited by the nucleic acid vaccine was low and repeated vaccinations did not boost the response. Injection of pcDNA3-45W into animals in which an immune response had previously been generated by vaccination with recombinant 45W using Quil A as adjuvant (rec45W vaccine), did not result in enhanced antibody levels. Initial vaccination with pcDNA3-45W and subsequently with the rec45W vaccine resulted in antibody levels significantly higher (P < 0.05) than those obtained in sheep which had only received the rec45W vaccine. This enhanced antibody response was predominantly of the IgG1 subclass (IgG1 : IgG2, 5 : 1) in animals injected with the nucleic acid vaccine by the i.m. route. Surprisingly, a second rec45W vaccination of these animals led to little or no increase in IgG1 levels and a 10-fold increase in IgG2 resulting in a predominance of 45W-specific IgG2 (IgG1 : IgG2, 0.25 1). These studies revealed that nucleic acid vaccination has efficacy, albeit limited, in the sheep and supports previous investigations which showed that antibody responses elicited by immunization are determined by both the route and mode of antigen delivery.
本报告描述了核酸疫苗在大型远交动物物种中单独使用以及与传统佐剂疫苗联合使用的情况。将编码绵羊寄生虫绵羊带绦虫的宿主保护性抗原（45W）的基因克隆到表达载体pcDNA3中，所得质粒称为pcDNA3 - 45W。15只绵羊中，11只通过肌肉注射或皮内注射pcDNA3 - 45W后，对45W产生了血清抗体反应，两种注射途径产生的抗体主要为IgG1。然而，核酸疫苗引发的抗体水平较低，重复接种并未增强反应。将pcDNA3 - 45W注射到先前已用Quil A作为佐剂接种重组45W（rec45W疫苗）产生免疫反应的动物中，并未导致抗体水平升高。先用pcDNA3 - 45W初免，随后用rec45W疫苗免疫，产生的抗体水平显著高于（P < 0.05）仅接受rec45W疫苗的绵羊。在通过肌肉注射途径接种核酸疫苗的动物中，这种增强的抗体反应主要为IgG1亚类（IgG1 : IgG2，5 : 1）。令人惊讶的是，对这些动物再次接种rec45W疫苗后，IgG1水平几乎没有增加或没有增加，而IgG2增加了10倍，导致45W特异性IgG2占主导（IgG1 : IgG2，0.25 : 1）。这些研究表明，核酸疫苗在绵羊中具有一定疗效，尽管有限，这支持了先前的研究，即免疫引发的抗体反应由抗原递送途径和方式共同决定。
