An emerging antibacterial nanovaccine for enhanced chemotherapy by selectively eliminating tumor-colonizing bacteria

Fusobacterium nucleatum (F. nucleatum), an oral anaerobe, is prevalent in colorectal cancer and is closely related to increased cancer cell growth, metastasis, and poor treatment outcomes. Bacterial vaccines capable of selectively eliminating bacteria present a promising approach to targeting intratumor F. nucleatum, thereby enhancing cancer treatment. Although adjuvants have been employed to enhance the immune response, the vaccine's effectiveness is constrained by inadequate T-cell activation necessary for eradicating intracellular pathogens. In this study, we developed a minimalistic, biomimetic nanovaccine by integrating highly immunostimulatory adjuvant cholesterol-modified CpG oligonucleotides into the autologously derived F. nucleatum membranes. Compared to the traditional vaccines consisting of inactivated bacteria and Alum adjuvant, the nanovaccine coupled with bacterial membranes and adjuvants could remarkably improve multiple antigens and adjuvant co-delivery to dendritic cells, maximizing their ability to achieve effective antigen presentation and strong downstream immune progress. Notably, the nanovaccine exhibits outstanding selective prophylactic and therapeutic effects, eliminating F. nucleatum without affecting intratumoral and gut microbiota. It significantly enhances chemotherapy efficacy and reduces cancer metastasis in F. nucleatum-infected colorectal cancer. Overall, this work represents the rational application of bacterial nanovaccine and provides a blueprint for future development in enhancing the antitumor effect against bacterial-infected cancer.