? The Immune Stimulant (IS) patch is an adjuvant delivery system designed to improve the potency and efficacy of parenteral injected vaccines. The IS-patch is formulated with a potent adjuvant as a dry self-adhesive patch, which is applied over the injection site, similar to a Band-Aid. The patch is designed to deliver heat labile enterotoxin (LT) adjuvant to skin dendritic cells. Preclinical and human clinical trials have demonstrated the safety of LT administered by the topical route and have clearly demonstrated the effectiveness of the IS-patch to potentiate systemic and mucosal immune responses elicited by injected vaccines. Considerable preclinical work has shown the IS-patch can be used to improve the potency of vaccines and, therefore, can be used to reduce vaccine dose and number of booster immunizations required for protective immunity. For vaccines in limited supply, the IS-patch can be used to extend the number of doses available including, for example, anthrax protective antigen vaccine and other vaccines under development for biodefense as well as vaccines that will be required to fight against new viral pathogens with pandemic potential such as influenza virus and SARS coronavirus. The elderly are a high-risk population with potential for high mortality and morbidity predicted. Clinical trials have already shown the benefit of the IS-patch for boosting immune responses in this population. The benefits to be gained by development of the IS-patch concept are evident. Therefore, the focus of this proposal is on the development of manufacturing processes for the IS-patch.
The specific aims are three fold: 1) to develop an optimized manufacturing process (cGMP) for producing LT-adjuvant at a cost effective commercial scale; 2) to optimize the IS-patch dry adhesive formulation and to scale-up the patch manufacturing process; and 3) in preclinical models of pandemic influenza and SARS coronavirus, establish the LT dose and dosing schedules that will be used to support the rationale for future clinical trial design and to generate preclinical safety information that will be used to support future IND submissions. It is important to consider new immunization strategies that will benefit the entire population by increasing the supply of vaccines that are limited and new strategies that will improve the effectiveness of vaccines to high-risk populations. ? ?
