Preparation and evaluation of a new combined conjugated vaccine against Klebsiella pneumonia and Pseudomonas aeruginosa

Bahy, Rehab; Fatyan, Eman; Saafan, Amal E.; El-Gebaly, Eman

doi:10.1111/jam.15646

Cited by 3 publications

(1 citation statement)

References 43 publications

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“…In addition to capsule, the components of LPS have also been considered for vaccine inclusion. Conjugate vaccines linking segments of LPS (other than the O-antigen) to a protein have been described (37, 38). These vaccines elicited antibodies; however, only one group demonstrated protection from a lethal K. pneumoniae challenge.…”

Section: Discussionmentioning

confidence: 99%

A heptavalent O-antigen bioconjugate vaccine exhibits differential functional antibody responses against diverseKlebsiella pneumoniaeisolates

Wantuch,

Knoot,

Robinson

et al. 2023

Preprint

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Klebsiella pneumoniaeis a concerning pathogen that is now the leading cause of neonatal sepsis and is increasingly difficult to treat due to heightened antibiotic resistance. Thus, there is an urgent need for preventive and effective immunotherapies targetingK. pneumoniae. Vaccination represents a tractable approach to combat this resistant bacterium in some settings; however, there is currently not a licensedK. pneumoniaevaccine available.K. pneumoniaesurface polysaccharides, including the terminal O-antigen polysaccharides of lipopolysaccharide, have long been attractive candidates for vaccine inclusion. Herein we describe the generation of a bioconjugate vaccine targeting seven of the predominant O-antigen subtypes inK. pneumoniae. Each of the seven bioconjugates were immunogenic in isolation, with limited cross-reactivity among subtypes. Vaccine-induced antibodies demonstrated varying degrees of binding to a wide variety ofK. pneumoniaestrains, including suspected hypervirulent strains, all expressing different O-antigen and capsular polysaccharide combinations. Further, sera from vaccinated mice induced complement-mediated killing of many of theseK. pneumoniaestrains. Finally, we found that increased quantity of capsule interferes with O-antigen antibodies’ ability to bind and mediate killing of someK. pneumoniaestrains, including those carrying hypervirulence-associated genes. Taken together, these data indicate that this novel heptavalent O-antigen bioconjugate vaccine formulation exhibits promising efficacy against some, but not all,K. pneumoniaeisolates.

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Section: Discussionmentioning

confidence: 99%

A heptavalent O-antigen bioconjugate vaccine exhibits differential functional antibody responses against diverseKlebsiella pneumoniaeisolates

Wantuch,

Knoot,

Robinson

et al. 2023

Preprint

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Klebsiella pneumoniae: adaptive immune landscapes and vaccine horizons

Wantuch,

Rosen

2023

Trends in Immunology

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

Miller,

Cross,

Tennant

et al. 2024

Vaccines

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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.

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Preparation and evaluation of a new combined conjugated vaccine against Klebsiella pneumonia and Pseudomonas aeruginosa

Cited by 3 publications

References 43 publications

A heptavalent O-antigen bioconjugate vaccine exhibits differential functional antibody responses against diverseKlebsiella pneumoniaeisolates

A heptavalent O-antigen bioconjugate vaccine exhibits differential functional antibody responses against diverseKlebsiella pneumoniaeisolates

Klebsiella pneumoniae: adaptive immune landscapes and vaccine horizons

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

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