The emergence of multidrug-resistant Klebsiella pneumoniae poses a grave threat to global public health, necessitating urgent strategies for vaccine development. In this context, computational tools have emerged as indispensable assets, offering unprecedented insights into klebsiellal biology and facilitating the design of effective vaccines. Here, a review of the application of computational methods in the development of K. pneumoniae vaccines is presented, elucidating the transformative impact of in silico approaches. Through a systematic exploration of bioinformatics, structural biology, and immunoinformatics techniques, the complex landscape of K. pneumoniae pathogenesis and antigenicity was unravelled. Key insights into virulence factors, antigen discovery, and immune response mechanisms are discussed, highlighting the pivotal role of computational tools in accelerating vaccine development efforts. Advancements in epitope prediction, antigen selection, and vaccine design optimisation are examined, highlighting the potential of in silico approaches to update vaccine development pipelines. Furthermore, challenges and future directions in leveraging computational tools to combat K. pneumoniae are discussed, emphasizing the importance of multidisciplinary collaboration and data integration. This review provides a comprehensive overview of the current state of computational contributions to K. pneumoniae vaccine development, offering insights into innovative strategies for addressing this urgent global health challenge.

01 Jul 2024·Vaccine

Vaccine value profile for Klebsiella pneumoniae

Article

Author: Bijsma, Merijn W ; Holt, Kathryn E ; Rosen, David A ; Moore, Catrin E ; Benson, Nicole ; Berkley, James A ; Reddy, Denasha ; Katwere, Michael ; Naylor, Nichola R ; Rodrigues, Charlene ; Micoli, Francesca ; Kwatra, Gaurav ; Srikantiah, Padmini ; Cross, Alan ; Hasso-Agopsowicz, Mateusz ; Broad, Jonathan ; Olwagen, Courtney ; Jit, Mark ; Madhi, Shabir A ; Duffy, Erin M ; O'Brien, Seamus ; Le Doare, Kirsty ; Iroh Tam, Pui-Ying ; Bielicki, Julia ; Dangor, Ziyaad ; Sadarangani, Manish ; Buurman, Ed T ; Nakabembe, Eve ; Mboizi, Robert ; Laxminarayan, Ramanan ; Karampatsas, Konstantinos ; Tennant, Sharon M

Klebsiella pneumoniae causes community- and healthcare-associated infections in children and adults. Globally in 2019, an estimated 1.27 million (95% Uncertainty Interval [UI]: 0.91-1.71) and 4.95 million (95% UI: 3.62-6.57) deaths were attributed to and associated with bacterial antimicrobial resistance (AMR), respectively. K. pneumoniae was the second leading pathogen in deaths attributed to AMR resistant bacteria. Furthermore, the rise of antimicrobial resistance in both community- and hospital-acquired infections is a concern for neonates and infants who are at high risk for invasive bacterial disease. There is a limited antibiotic pipeline for new antibiotics to treat multidrug resistant infections, and vaccines targeted against K. pneumoniae are considered to be of priority by the World Health Organization. Vaccination of pregnant women against K. pneumoniae could reduce the risk of invasive K.pneumoniae disease in their young offspring. In addition, vulnerable children, adolescents and adult populations at risk of K. pneumoniae disease with underlying diseases such as immunosuppression from underlying hematologic malignancy, chemotherapy, patients undergoing abdominal and/or urinary surgical procedures, or prolonged intensive care management are also potential target groups for a K. pneumoniae vaccine. A 'Vaccine Value Profile' (VVP) for K.pneumoniae, which contemplates vaccination of pregnant women to protect their babies from birth through to at least three months of age and other high-risk populations, provides a high-level, holistic assessment of the available information to inform the potential public health, economic and societal value of a pipeline of K. pneumoniae vaccines and other preventatives and therapeutics. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public-private partnerships, and multi-lateral organizations, and in collaboration with stakeholders from the WHO. All contributors have extensive expertise on various elements of the K.pneumoniae VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information.

01 Mar 2024·Heliyon

Designing a conjugate vaccine targeting Klebsiella pneumoniae ST258 and ST11

Article

Author: Li, Danyang ; Li, Min ; Lin, Zihan ; Yu, Mingkai ; Shi, Liuzhi ; Zhao, Min ; Yuan, Yigang ; Ye, Daijiao

Klebsiella pneumoniae (K. pneumoniae) is a common bacterium that can cause iatrogenic infection. Recently, the rise of antibiotic resistance among K. pneumoniae strains is one key factor associated with antibiotic treatment failure. Hencefore, there is an urgent need for effective K. pneumoniae vaccines. This study aimed to design a multi-epitope vaccine (MEV) candidate against K. pneumonia by utilizing an immunoinformatics method. In this study, we obtained 15 cytotoxic T lymphocyte epitopes, 10 helper T lymphocyte epitopes, 6 linear B-cell epitopes, and 2 conformational B-cell epitopes for further research. Then, we designed a multi-epitope vaccine composed of a total of 743 amino acids, containing the epitopes linked by GPGPG flexible links and an EAAAK linker to the Cholera Toxin Subunit B coadjuvant. The observed properties of the MEV, including non-allergenicity, high antigenicity, and hydrophilicity, are noteworthy. The improvements in the tertiary structure through structural refinement and disulfide bonding, coupled with promising molecular interactions revealed by molecular dynamics simulations with TLR4, position the MEV as a strong candidate for further investigation against K. pneumoniae.

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Indication	Highest Phase	Country/Location	Organization	Date
Bacteremia	Preclinical	United States	Pylum Biosciences, Inc.	19 Jan 2024

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