A self assembled nanofibrous structure as a novel vaccine adjuvant

Abstract

Vaccination is the most effective and cost-efficient way of protection against the major infectious diseases but ideal vaccine formulation has not been found. Recent vaccine systems are mainly composed of two major substitutes that are antigen and adjuvant. Recently it was demonstrated that widely used adjuvants exhibit some safety problems that affect the neural system such as neurotoxicity and autoimmune diseases. Therefore, there are increased concerns about side effects of the adjuvants and many researchers focus on developing new adjuvants that are effective and safe. Peptide amphiphiles are chemically defined molecules that are able to self-assemble into nanofibrous structures. The nanofibrous structures are biocompatible, biodegradable, and biosafe and thereby they are ideal for vaccine systems. Also, nanofibrous structures don’t contain any substance that are potentially dangerous for neural system such as metals. Thus, nanofibrous structures are promising candidates to be alternative novel vaccine adjuvants. In this thesis, I investigated the potential of a biotinylated nanofibrous structure as a novel vaccine adjuvant that is potentially safe. Briefly, biotinylated peptide amphiphiles were synthesized, purified and characterized to analyze the features of the novel material. The peptide amphiphiles were induced to form nanofibrous structures by self-assembly and antigens (ovalbumin) were bound to the biotinylated nanofibrous structures through streptavidin linkers. Splenocytes were treated with the nanofibrous structures to demonstrate the effects of the nanofibrous structures on the immune response. After the confirmation of efficient immune response that are induced by the nanofibrous structure in vitro, as enhancing release of stimulatory cytokines, inducing dendritic cell maturation and triggering the cross-presentation of the antigen, mice were immunized with the nanofibrous structure in the presence of antigen for further analysis of the nanofibrous structure efficiency as adjuvant in vivo. Both in vivo and in vitro results showed that the nanofibrous structure is able to effectively trigger the antigen specific immune response and thereby exhibit adjuvant properties. Overall, I suggest that the nanofibrous structure is able to be used as a new vaccine adjuvant that induces effective antigen specific adoptive immune response and thereby it could be a good alternative of recently used adjuvants that are suspected to contribute some impairments in neural system.