In this study, we propose the use of antigen-expressing immunostimulatory liposomes (AnExILs) as artificial microbes for vaccination (Fig. 1) . The potential advantages of such antigen-expressing immunostimulatory liposomes (AnExILs) over conventional vaccines are numerous: the specificity of the vaccine can be easily altered by simply changing the DNA templates without having to change the entire vaccine formulation. Moreover, compared to DNA vaccines AnExILs do not exclusively rely on the often inefficient transfection of DNA into cells of the vaccine recipient in order to be effective. Secondly, compared to vector-based vaccines, AnExILs will be unaffected by neutralizing antibodies against the vector. Thirdly, there is no limit to the number of genes that can be expressed inside AnExILs. Lastly, AnExILs mimic characteristics of viruses and bacteria without the safety concerns related to the use of attenuated pathogens for vaccination. Here, we show that AnExILs expressing b-galactosidase are well tolerated after i.m. injection and were capable of inducing strong systemic immune responses, which were superior to that of liposomal DNA or protein vaccines encoding the same antigen.