Current Stage in the Development of Klebsiella pneumoniae Vaccines

Abstract

Klebsiella pneumoniae is a bacterium capable of colonizing mucous membranes, causing serious infections. Widespread antibiotic resistance in K. pneumoniae-either through intrinsic mechanisms or via acquisition from different species, especially in hospital environments-limits the therapeutic options against this pathogen, further aggravating the disease burden. To date, there are no vaccines available against K. pneumoniae infection. Although formulations based on capsular polysaccharides have been proposed, the high variability in capsular serotypes limits vaccine coverage. Recombinant vaccines based on surface exposed bacterial antigens are a promising alternative owing to their conservation among different serotypes and accessibility to the immune system. Many vaccine candidates have been proposed, some of which have reached clinical trials. The present review summarizes the current status of K. pneumoniae vaccine development. Different strategies including whole cell vaccines, outer membrane vesicles (OMVs), ribosome, polysaccharide, lipopolysaccharide (LPS), and protein-based formulations are discussed. The contribution of antibody and cell-mediated responses is also presented. In summary, K. pneumoniae vaccines are feasible and a promising strategy to prevent infections and to reduce the antimicrobial resistance burden worldwide.

Genomic dissection of the bacterial population underlyingKlebsiella pneumoniaeinfections in hospital patients: insights into an opportunistic pathogen

“…Capsule (K) and LPS (O) antigens have been proposed as targets for vaccination against K. pneumoniae infection 64 . K biosynthesis loci were confidently identified for n=284 (96.6%) infection episodes, spanning 91 distinct K locus (KL) types (including 4 novel loci, KL167-170, see Table S4).…”

Kaptive 2.0: updated capsule and lipopolysaccharide locus typing for the Klebsiella pneumoniae species complex

“…K. pneumoniae with resistance to the third-generation cephalosporins and carbapenems are disseminating globally and of particular concern because they cause infections with very limited treatment options. As a consequence, there is increasing interest in developing novel anti-KpSC control strategies such as vaccines, phage and monoclonal antibody therapies [6][7][8][9].…”

Vaccines for healthcare associated infections without vaccine prevention to date

“…First, a great part of HAIs is caused by commensal pathogens present prior to hospitalization (endogenous infections). Consequently, vaccination of patients during hospitalization comes too late, and immune response could be impaired by pre-existing immunity and tolerance to microbiota [ 77 ]. Secondly, definition of the at-risk populations, and anticipation of the at-risk situations (scheduled surgery, immunosuppressive agents, hemodialysis) are crucial.…”

“…Different vaccine strategies against K. pneumoniae have been investigated: whole cell vaccines and mixed bacterial vaccines, capsular polysaccharides, Outer Membrane Vesicles (containing lipids, cell wall structures, nucleic acids, and toxins), proteins based formulations (outer membrane proteins, toxins, other proteins like siderophores), ribosomal vaccines [ 77 ]. A tetravalent bioconjugate vaccine including O antigen-polysaccharides (GSK) is entering in clinical phases with a Phase I/II trial [ 78 ].…”

“…To our knowledge, it is the unique K. pneumoniae currently under clinical development. Mixed bacterial vaccines were already investigated with heterogeneous results [ 77 ].…”