Anthrax DNA vaccine for non-invasive immunization on skin

描述（由申请人提供）：虽然炭疽杆菌的自然感染很罕见，但炭疽孢子可以通过许多不同的方式作为生物武器有效地传播，例如9月11日袭击后发生的美国邮件表面污染。因此，需要有效的炭疽预防方法。美国目前的炭疽疫苗，吸附炭疽疫苗（AVA）具有许多缺点，包括需要多次注射，随后每年进行加强。新的炭疽疫苗开发一直集中在生产基于炭疽毒素的保护性抗原（PA）成分的疫苗。用PA编码质粒DNA疫苗在皮肤上进行局部非侵入性免疫接种更方便、患者友好、成本效益高，因此在紧急情况下对大量人群进行免疫接种可能更可行。然而，这种免疫途径的免疫应答往往相当弱。我们自己的初步研究强烈表明，我们开发的基于微乳液的DNA疫苗载体显着增强了DNA疫苗的免疫应答，包括PA 63基因编码的DNA疫苗，当局部非侵入性地应用于小鼠皮肤上时。因此，该微乳液可潜在地用于在人类中局部施用炭疽DNA疫苗。然而，在考虑将这种疫苗作为预防人类炭疽感染的预防性可能性之前，迫切需要鉴定这种DNA疫苗掺入的微乳液的免疫诱导/增强机制，并验证诱导的抗PA免疫应答的功效。我们的长期目标是开发一种有效的、非侵入性的局部炭疽疫苗。本申请的具体目的是鉴定该DNA疫苗掺入的微乳液的免疫诱导机制，并评价小鼠模型中诱导的抗PA免疫应答的活性。中心假设是PA编码质粒DNA掺入的微乳液，当局部应用于皮肤上时，将通过增强小鼠毛囊中编码PA基因的摄取和表达而引起强烈的抗PA免疫应答。该项目的成功完成有望为这种微乳DNA疫苗在人体临床试验中的应用提供科学可靠的基础。有效的局部炭疽疫苗将有助于保护和改善公众健康。此外，该疫苗免疫诱导机制的阐明和其效力的证明将使该微乳在开发其他人和动物疾病的疫苗中得以应用。

DESCRIPTION (provided by applicant): Although a natural infection by Bacillus anthracis is rare, anthrax spores can be effectively distributed as biological weapons in many different means, such as the surface contamination of the U.S. mail occurred in the post September 11 attacks. Thus, effective approaches for anthrax prophylaxis are needed. The current anthrax vaccine in the U.S., the anthrax vaccine adsorbed (AVA), has many drawbacks including the requirement for multiple injections with subsequent annual boosters. New anthrax vaccine developments have been focused on the production of a vaccine based on the protective antigen (PA) component of the anthrax toxin. Topical non-invasive immunization onto the skin with a PA-encoding plasmid DNA vaccine is more convenient, patient friendly, cost-effective, and thus, may be more feasible for the immunization of a large population of people in case of an emergency. However, the immune response from this route of immunization is often rather weak. Our own preliminary studies strongly suggest that a microemulsion-based DNA vaccine carrier developed by us significantly enhanced the immune response from DNA vaccines, including a PA63 gene encoding DNA vaccine, when topically, non-invasively applied onto the skin of mice. Thus, this microemulsion could potentially be used to topically administer an anthrax DNA vaccine in humans. However, there is a critical need to identify the mechanisms of immune induction/enhancement by this DNA vaccine-incorporated microemulsion and to validate the efficacy of the anti-PA immune response induced before considering such a vaccine as a prophylactic possibility for the prevention of an anthrax infection in humans. Our long-term objective is to develop an efficacious, non-invasive, topical anthrax vaccine. The specific aims in this particular application are to identify the mechanisms involved in the immune induction by this DNA vaccine-incorporated microemulsion and to evaluate the activity of the anti-PA immune response induced in a mouse model. The central hypothesis is that the PA-encoding plasmid DNA-incorporated microemulsion, when topically applied onto the skin, will elicit strong anti-PA immune responses by enhancing the uptake and expression of the encoding PA gene in hair follicles in mice. The successful completion of this project is expected to provide a scientifically sound foundation for the use of this microemulsion-based DNA vaccine in human clinical trials. An effective topical anthrax vaccine will contribute to the protection and improvement of public health. Moreover, the elucidation of the mechanism of immune induction by this vaccine and the demonstration of its efficacy will enable the application of this microemulsion in developing vaccines for other human and animal diseases.