Demand for New Adjuvants
Although there are many compounds (e.g. cholera toxin, heat-labile enterotoxin) that demonstrate exceptional adjuvant activity in animal studies, their toxicity and poor physicochemical properties have restricted their use in human vaccines. In spite of the critical role that adjuvants play in vaccine development, the aluminum salts (generally referred to as “alum”) remain as the only FDA- approved vaccine adjuvant for human vaccination for the last 70 years with the exception of two new adjuvants that gained limited approval (MF59 in Europe and ASO3 in the US).
Alum is generally effective in the traditional vaccine approach where triggering strong and systemic antibody responses would confer protection. On the other hand, not all vaccines show enhanced antigenicity when adsorbed to alum (e.g. pertussis and typhoid fever). Alum (or aluminum salts in general) also show poor adjuvant effect in new vaccine strategies particularly with protein based subunit antigens. Further, alum has little or no capacity to stimulate cellular or Th1-type immune responses which are most critical for protection against intracellular pathogens. Also, being an inflammatory chemical, aluminum adjuvants may cause severe local irritation and stimulate IgE expression, which promotes serious systemic and local allergic reactions including eosinophilia, tissue irritation, granumolas, abscesses, or subcutaneous nodules at the site of administration.
Another major drawback with aluminum adjuvants, and others is that they are suitable and approved only for parenteral administration that generally triggers systemic immune responses but rarely induces mucosal immune responses. Currently there is no vaccine adjuvant that is approved for mucosal administration in humans.
The lack of choice for safer, non-toxic, and effective vaccine adjuvants and delivery systems capable of inducing an optimized B cell immune responses and generating appropriate T-cell responses still remains as a major obstacle in the development of efficacious new vaccines to address previously unmet or neglected life-threatening infectious diseases. The induction of mucosal immunity is also desired to induce the first line of protective local immunity against mucosally transmitted pathogens. Availability of such an adjuvant could change the paradigm for vaccine development and immunization practices. We propose that CaPtivate's nanoparticles demonstrate the potential to be that adjuvant.
