Nanovaccines hold significant promise for the prevention and treatment of infectious diseases. However, the efficacy of many nanovaccines is often limited by inadequate stimulation of both innate and adaptive immune responses. Herein, we explore a rational vaccine strategy aimed at modulating innate cell microenvironments within lymph nodes (LNs) to enhance the generation of effective immune responses. Inspired by the structure and natural infection process of viruses, we developed a versatile antigen and adjuvant co-delivery platform, termed virus-mimetic vaccines (VMVs). Specifically, polyarginine-tagged antigens were noncovalently assembled onto nucleic acid nanogels containing cytosine-phosphate-guanine oligodeoxynucleotide via a salt-bridge zipper mechanism, which can activate Toll-like receptor 9. Upon intramuscular immunization, VMVs effectively drained into the LNs, recruiting and activating multiple innate cells, including CD8