Vaccines represent the most relevant contribution of immunology to human health.However,despite the remarkable success achieved in the past years,many vaccines are still missing in order to fight important human pathologies and to prevent emerging and re-emerging diseases.For these pathogens the known strategies for making vaccines have been unsuccessful and thus,new avenues should be investigated to overcome the failure of clinical trials and other important issues including safety concerns related to live vaccines or viral vectors,the weak immunogenicity of subunit vaccines and side effects associated with the use of adjuvants.A major hurdle of developing successful and effective vaccines is to design antigen delivery systems in such a way that optimizes antigen presentation and induces broad protective immune responses.Recent advances in vector delivery technologies,immunology,vaccinology and system biology,have led to a deeper understanding of the molecular and cellular mechanisms by which vaccines should stimulate both arms of the adaptive immune responses,offering new strategies of vaccinations.This review is an update of current strategies with respect to live attenuated and inactivated vaccines,DNA vaccines,viral vectors,lipid-based carrier systems such as liposomes and virosomes as well as polymeric nanoparticle vaccines and virus-like particles.In addition,this article will describe our work on a versatile and immunogenic delivery system which we have studied in the past decade and which is derived from a nonpathogenic prokaryotic organism:the“E2 scaffold”of the pyruvate dehydrogenase complex from Geobacillus stearothermophilus.