Recent advancement, immune responses, and mechanism of action of various vaccines against intracellular bacterial infections

Emerging and re-emerging bacterial infections are a serious threat to human and animal health. Extracellular bacteria are free-living, while facultative intracellular bacteria replicate inside eukaryotic host cells. Many serious human illnesses are now known to be caused by intracellular bacteria such as Salmonella enterica, Escherichia coli, Staphylococcus aureus, Rickettsia massiliae, Chlamydia species, Brucella abortus, Mycobacterium tuberculosis and Listeria monocytogenes, which result in substantial morbidity and mortality. Pathogens like Mycobacterium, Brucella, MRSA, Shigella, Listeria, and Salmonella can infiltrate and persist in mammalian host cells, particularly macrophages, where they proliferate and establish a repository, resulting in chronic and recurrent infections. The current treatment for these bacteria involves the application of narrow-spectrum antibiotics. FDA-approved vaccines against obligate intracellular bacterial infections are lacking. The development of vaccines against intracellular pathogenic bacteria are more difficult because host defense against these bacteria requires the activation of the cell-mediated pathway of the immune system, such as CD8+ T and CD4+ T. However, different types of vaccines, including live, attenuated, subunit, killed whole cell, nano-based and DNA vaccines are currently in clinical trials. Substantial development has been made in various vaccine strategies against intracellular pathogenic bacteria. This review focuses on the mechanism of intracellular bacterial infection, host immune response, and recent advancements in vaccine development strategies against various obligate intracellular bacterial infections.