Design and development of adjuvant-active nonionic block copolymers.

Abstract

Nonionic block copolymers are surfactants synthesized using propylene oxide and ethylene oxide, and they can be designed so that individual copolymers have unique vaccine adjuvant properties. We have designed and produced nonionic block copolymers based on high molecular weight (MW), 9-15 kDA, cores of poly(oxypropylene) (POP) coupled with smaller poly(oxyethylene) (POE) end blocks. Copolymers synthesized with less than 10% (w/w) POE will spontaneously assemble into 300 nm-3 microm micelles or microparticles in aqueous solutions at physiological pH, and when formulated with protein, complex microparticles consisting of both the protein and copolymers are formed. The adjuvant activity of nonionic block copolymers is influenced by both size and POE content; maximal activity is associated with low POE content, 5-10%, and a molecular size of 11-12 kDa. The type of immune response produced is also influenced by the POE content. Copolymers with 10% POE significantly augmented Type 2 helper T-lymphocyte responses whereas copolymers with lower POE contents augmented both Type 1 and Type 2 helper T-lymphocyte responses. This property allows for vaccines to be "customized" by using adjuvant-active nonionic block copolymers that will augment the most appropriate types of immune responses.