Metallo-β-lactamase NDM-1 serves as a universal vaccine candidate for combatting antimicrobial resistance

The rapid emergence and spread of antimicrobial resistance have become critical global health issues, leading to significant morbidity and mortality worldwide. With the increase in resistance to multiple drugs, especially frontline clinical antibiotics, there is an urgent need for novel and effective alternative strategies. Herein, we developed a vaccine targeting the antimicrobial resistance enzyme NDM-1, which was first identified in Klebsiella pneumoniae and has quickly spread to other gram-negative bacteria. Our results demonstrate that NDM-1 primarily triggers a humoral immune response and effectively protects mice from lethal Klebsiella pneumoniae infection, as evidenced by increased survival rates, reduced bacterial loads, and decreased lung inflammation in mice. The specific antibodies generated were able to inhibit the enzymatic activity of NDM-1, bacterial growth, and exhibit opsonophagocytic activity against Klebsiella pneumoniae in vitro. Both active and passive immunization with NDM-1 showed an additive effect when combined with meropenem therapy. Furthermore, NDM-1 immunization induced cross-reactivity with NDM-1 variants, potentially providing broad protection against bacteria carrying different NDM genes. Additionally, heptamerization of NDM-1 improved its immunogenicity and protective efficacy in mice. These results highlight the potential of vaccine development based on antibiotic resistance candidates for broadly combatting antimicrobial resistance.