Abstract
Antimicrobial resistance poses a grave threat to global public health. Although new antibiotics are urgently needed, most share resistance mechanisms with existing drugs, thereby necessitating the development of alternative antibacterial therapeutics. Various immunotherapeutic agents, including monoclonal antibodies, therapeutic vaccines, cellular therapies, and immunomodulators, have been developed and explored to treat drug-resistant bacterial infections. This review comprehensively summarizes recent advancements in immunotherapies and vaccine-based approaches as alternative strategies to combat drug-resistant bacterial infections. Our findings indicate that immunotherapy offers several advantages over traditional antibiotics, such as enhanced specificity, long-term effects, overcoming resistance mechanisms, broad applicability, potential for combination therapies, personalized medicine, and reduced toxicity. Also, formulation and delivery strategies, including nanoparticles, liposomes, cellular vehicles, and diverse administration routes, have been employed to improve the efficacy and targeting of these immunotherapeutic agents. In-depth evaluations of promising preclinical and clinical studies demonstrate their potential effectiveness against pathogens such as Pseudomonas aeruginosa, Escherichia coli, Mycobacterium tuberculosis, Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, Acinetobacter baumannii, and Helicobacter pylori. These suggest that immunotherapy is a promising alternative to address the growing challenge of drug-resistant bacterial infections, potentially revolutionizing infection management strategies.