Klebsiella pneumoniae Lipopolysaccharide as a Vaccine Target and the Role of Antibodies in Protection from Disease

Abstract

Klebsiella pneumoniae is well recognized as a serious cause of infection in healthcare-associated settings and immunocompromised individuals; however, accumulating evidence from resource-limited nations documents an alarming rise in community-acquired K. pneumoniae infections, manifesting as bacteremia and pneumonia as well as neonatal sepsis. The emergence of hypervirulent and antibiotic-resistant K. pneumoniae strains threatens treatment options for clinicians. Effective vaccination strategies could represent a viable alternative that would both preempt the need for antibiotics to treat K. pneumoniae infections and reduce the burden of K. pneumoniae disease globally. There are currently no approved K. pneumoniae vaccines. We review the evidence for K. pneumoniae lipopolysaccharide (LPS) as a vaccine and immunotherapeutic target and discuss the role of antibodies specific for the core or O-antigen determinants within LPS in protection against Klebsiella spp. disease. We expand on the known role of the Klebsiella spp. capsule and O-antigen modifications in antibody surface accessibility to LPS as well as the in vitro and in vivo effector functions reported for LPS-specific antibodies. We summarize key hypotheses stemming from these studies, review the role of humoral immunity against K. pneumoniae O-antigen for protection, and identify areas requiring further research.