Abstract:The bacteria causing pneumonia are capable of forming biofilms. These biofilms could confer resistance to antibiotics and are difficult to be eradicated. The formation of certain bacterial biofilms is closely related to bacterial capsules. Under the synergistic action of capsules and biofilms, pathogens could evade host immune clearance. The specific strategies involve three aspects. Firstly, pathogens depend on the physical barrier effect of capsules to prevent the deposition of complements in the lungs and the binding of antibodies, which hinder the phagocytosis of alveolar macrophages. In addition, the physical barrier effect obscures the underlying immunogenic structures. Secondly, in the event of a mutation of the capsular polysaccharide (CPS) structure, there is an attendant effect on the recognition of pathogens by antibodies. It has been demonstrated that the immune responses exhibited by the lungs can be modulated by CPS through surface modifications. Finally, the structural composition of bacterial biofilms impedes the diffusion and penetration of antibiotics within the infection site, thereby impeding their penetration into the lung tissue. At the same time, pathogens down-regulate the expression of virulence genes in biofilms to establish localized immune tolerance. This review emphasizes that pathogens employ multiple complementary strategies to achieve immune evasion and explores the translational potential of enzymatic-immune synergistic systems targeting biofilm matrices for novel vaccine design. The study is expected to give new insights into the breakthroughs in conventional anti-infection strategies and the development of novel vaccines.