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A subunit vaccine against pneumonia: targeting Streptococcus pneumoniae and Klebsiella pneumoniae.

ABSTRACT: Community-acquired pneumonia is primarily caused by Streptococcus pneumoniae and Klebsiella pneumoniae, two pathogens that have high morbidity and mortality rates. This is largely due to bacterial resistance development against current antibiotics and the lack of effective vaccines. The objective of this work was to develop an immunogenic multi-epitope subunit vaccine capable of eliciting a robust immune response against S. pneumoniae and K. pneumoniae. The targeted proteins were the pneumococcal surface proteins (PspA and PspC) and choline-binding protein (CbpA) of S. pneumoniae and the outer membrane proteins (OmpA and OmpW) of K. pneumoniae. Different computational approaches and various immune filters were employed for designing a vaccine. The immunogenicity and safety of the vaccine were evaluated by utilizing many physicochemical and antigenic profiles. To improve structural stability, disulfide engineering was applied to a portion of the vaccine structure with high mobility. Molecular docking was performed to examine the binding affinities and biological interactions at the atomic level between the vaccine and Toll-like receptors (TLR2 and 4). Further, the dynamic stabilities of the vaccine and TLRs complexes were investigated by molecular dynamics simulations. While the immune response induction capability of the vaccine was assessed by the immune simulation study. Vaccine translation and expression efficiency was determined through an in silico cloning experiment utilizing the pET28a(+) plasmid vector. The obtained results revealed that the designed vaccine is structurally stable and able to generate an effective immune response to combat pneumococcal infection.

Supplementary information

The online version contains supplementary material available at 10.1007/s13721-023-00416-3.

SUBMITTER: Rafi MO

PROVIDER: S-EPMC10115389 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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A subunit vaccine against pneumonia: targeting Streptococcus pneumoniae and Klebsiella pneumoniae.

Rafi Md Oliullah MO Al-Khafaji Khattab K Mandal Santi M SM Meghla Nigar Sultana NS Biswas Polash Kumar PK Rahman Md Shahedur MS

Network modeling and analysis in health informatics and bioinformatics 20230419 1

Community-acquired pneumonia is primarily caused by Streptococcus pneumoniae and Klebsiella pneumoniae, two pathogens that have high morbidity and mortality rates. This is largely due to bacterial resistance development against current antibiotics and the lack of effective vaccines. The objective of this work was to develop an immunogenic multi-epitope subunit vaccine capable of eliciting a robust immune response against S. pneumoniae and K. pneumoniae. The targeted p ...[more]

PMID: 37096010

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Project description:Klebsiella pneumoniae is an opportunistic Gram-negative bacterium that has become a leading causative agent of nosocomial infections, mainly infecting patients with immunosuppressive diseases. Capsular (K) serotypes K1, K2, K47, and K64 are commonly associated with higher virulence (hypervirulent Klebsiella pneumoniae), and more threateningly, isolates belonging to the last two K serotypes are also frequently associated with resistance to carbapenem (hypervirulent carbapenem-resistant Klebsiella pneumoniae). The prevalence of these isolates has posed significant threats to human health, and there are no appropriate therapies available against them. Therefore, in this study, a method combining immunoinformatics and pangenome analysis was applied for contriving a multiepitope subunit vaccine against these four threatening serotypes. To obtain cross-protection, 12 predicted conserved antigens were screened from the core genome of 274 complete Klebsiella pneumoniae genomes (KL1, KL2, KL47, and KL64), from which the epitopes of T and B cells were extracted for vaccine construction. In addition, the immunological properties, the interaction with Toll-like receptors, and the stability in a simulative humoral environment were evaluated by immunoinformatics methods, molecular docking, and molecular dynamics simulation. All of these evaluations indicated the potency of this constructed vaccine to be an effective therapeutic agent. Lastly, the cDNA of the designed vaccine was optimized and ligated to pET-28a(+) for expression vector construction. Overall, our research provides a newly cross-protective control strategy against these troublesome pathogens and paves the way for the development of a safe and effective vaccine. IMPORTANCE Klebsiella pneumoniae is an opportunistic Gram-negative bacterium that has become a leading causative agent of nosocomial infections. Among the numerous capsular serotypes, K1, K2, K47, and K64 are commonly associated with higher virulence (hypervirulent K. pneumoniae). More threateningly, the last two serotypes are frequently associated with resistance to carbapenem (hypervirulent carbapenem-resistant K. pneumoniae). However, there is currently no therapeutic agent or vaccine specifically against these isolates. Therefore, development of a vaccine against these pathogens is very essential. In this study, for the first time, a method combining pangenome analysis, reverse vaccinology, and immunoinformatics was applied for contriving a multiepitope subunit vaccine against K. pneumoniae isolates of K1, K2, K47, and K64. Also, the immunological properties of the constructed vaccine were evaluated and its high potency was revealed. Overall, our research will pave the way for the vaccine development against these four threatening capsular serotypes of K. pneumoniae.

Dataset Information

A subunit vaccine against pneumonia: targeting Streptococcus pneumoniae and Klebsiella pneumoniae.

Supplementary information

Publications

A subunit vaccine against pneumonia: targeting S<i>treptococcus pneumoniae</i> and <i>Klebsiella pneumoniae</i>.

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