Production of a Promising Biosynthetic Self‐Assembled Nanoconjugate Vaccine against <i>Klebsiella Pneumoniae</i> Serotype O2 in a General <i>Escherichia Coli</i> Host

Peng, Zhehui; Wu, Jun; Wang, Kangfeng; Li, Xin; Sun, Peng; Zhang, Lulu; Huang, Jing; Liu, Yan; Hua, Xiaoting; Yu, Yunsong; Pan, Chao; Wang, Hengliang; Zhu, Li

doi:10.1002/advs.202100549

Cited by 30 publications

(26 citation statements)

References 59 publications

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“…This particle was about 25 nm, which prolonged retention in draining lymph nodes and could stimulate strong cellular and humoral immune responses. Further, the system could be introduced into a modified E. coli host to prepare exogenous pathogenic bacteria, such as Klebsiella pneumoniae , nano-scaled conjugate vaccine and protect mice from systemic and pulmonary infection ( 285 ). Polysaccharide conjugate vaccine is considered the most successful bacterial vaccine at present.…”

Section: Protein-based Bacterial Vaccine Delivery Systemmentioning

confidence: 99%

Peptide-Based Vaccines for Tuberculosis

Gong

Pan²,

Cheng

et al. 2022

Front. Immunol.

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Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. As a result of the coronavirus disease 2019 (COVID-19) pandemic, the global TB mortality rate in 2020 is rising, making TB prevention and control more challenging. Vaccination has been considered the best approach to reduce the TB burden. Unfortunately, BCG, the only TB vaccine currently approved for use, offers some protection against childhood TB but is less effective in adults. Therefore, it is urgent to develop new TB vaccines that are more effective than BCG. Accumulating data indicated that peptides or epitopes play essential roles in bridging innate and adaptive immunity and triggering adaptive immunity. Furthermore, innovations in bioinformatics, immunoinformatics, synthetic technologies, new materials, and transgenic animal models have put wings on the research of peptide-based vaccines for TB. Hence, this review seeks to give an overview of current tools that can be used to design a peptide-based vaccine, the research status of peptide-based vaccines for TB, protein-based bacterial vaccine delivery systems, and animal models for the peptide-based vaccines. These explorations will provide approaches and strategies for developing safer and more effective peptide-based vaccines and contribute to achieving the WHO’s End TB Strategy.

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Section: Protein-based Bacterial Vaccine Delivery Systemmentioning

confidence: 99%

Peptide-Based Vaccines for Tuberculosis

Gong

Pan²,

Cheng

et al. 2022

Front. Immunol.

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“…According to our results, the immune response is greatly improved when the peptide antigen is fused with CTB, suggesting that the carrier plays an important role in the enhancement of antigen immunogenicity. The same effect can be found in conjugate vaccines, which are produced by coupling the weakly immunogenic polysaccharide antigen with carrier protein ( 37 – 39 ). Polysaccharide antigens could be transformed from TI antigen to TD antigen with the help of carriers ( 40 – 42 ).…”

Section: Discussionmentioning

confidence: 71%

A Short Peptide of Autotransporter Ata Is a Promising Protective Antigen for Vaccination Against Acinetobacter baumannii

Sun

Pan³

et al. 2022

Front. Immunol.

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With the emergence of multidrug-resistant strains, Acinetobacter baumannii infection is becoming a thorny health problem in hospitals. However, there are no licensed vaccines against A. baumannii. Acinetobacter trimeric autotransporter (Ata) is an important known virulence factor located on the outer membrane of bacteria. Herein, we carried out a series of experiments to test the immunogenicity of a short C-terminal extracellular region of Ata (Ataα, only containing 39 amino acids) in a murine model. The short peptide Ataα was fused with the cholera toxin B subunit (CTB), which has been reported to have immunoadjuvant activity. The fusion protein showed no inflammation and organ damages, and have the ability to elicit both Th1 and Th2 immune responses in mice. The bactericidal activities against A. baumannii and prophylactic effects of the fusion protein were further evidenced by a significant reduction in the bacterial load in the organs and blood. In addition, the candidate vaccine could provide broad protection against lethal challenges with a variety of A. baumannii strains. Moreover, when CpG was added on the basis of aluminum adjuvant, the immune response, especially cellular immunity, could be further strengthened. Overall, these results revealed that the Ataα is a promising vaccine target against A. baumannii infection.

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“…Several recent studies have proposed putative vaccine candidates, most notably polysaccharides such as capsule or O-antigen, for inclusion into polysaccharide-protein conjugate vaccines (8)(9)(10). O-antigen remains a leading candidate for incorporation into a vaccine, and at least one tetravalent O-antigen-based bioconjugate vaccine is currently in Phase I trials (11).…”

Section: Introductionmentioning

confidence: 99%

Capsular polysaccharide inhibits vaccine-induced O-antigen antibody binding and function across both classical and hypervirulent K2:O1 strains ofKlebsiella pneumoniae

Wantuch¹,

Knoot²,

Robinson³

et al. 2022

Preprint

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Klebsiella pneumoniae presents as two circulating pathotypes: classical K. pneumoniae (cKp) and hypervirulent K. pneumoniae (hvKp). Classical isolates are considered urgent threats due to their antibiotic resistance profiles, while hvKp isolates have historically been antibiotic susceptible. Recently, however, increased rates of antibiotic resistance have been observed in both hvKp and cKp, further underscoring the need for preventive and effective immunotherapies. Two distinct surface polysaccharides have gained traction as vaccine candidates against K. pneumoniae: capsular polysaccharide and the O-antigen of lipopolysaccharide. While both targets have practical advantages and disadvantages, it remains unclear which of these antigens included in a vaccine would provide superior protection against matched K. pneumoniae strains. Here, we report the production of two bioconjugate vaccines, one targeting the K2 capsular serotype and the other targeting the O1 O-antigen. Using murine models, we investigated whether these vaccines induced specific antibody responses that recognize K2:O1 K. pneumoniae strains. While each vaccine was immunogenic in mice, both cKp and hvKp strains exhibited decreased O-antibody binding in the presence of capsule. Further, O1 antibodies demonstrated decreased killing in serum bactericidal assays with encapsulated strains, suggesting that the presence of K. pneumoniae capsule blocks O1-antibody binding and function. Finally, the K2 vaccine outperformed the O1 vaccine against both cKp and hvKp in two different murine infection models. These data suggest that capsule-based vaccines may be superior to O-antigen vaccines for targeting hvKp and some cKp strains, due to capsule blocking the O-antigen.

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Production of a Promising Biosynthetic Self‐Assembled Nanoconjugate Vaccine against Klebsiella Pneumoniae Serotype O2 in a General Escherichia Coli Host

Cited by 30 publications

References 59 publications

Peptide-Based Vaccines for Tuberculosis

Peptide-Based Vaccines for Tuberculosis

A Short Peptide of Autotransporter Ata Is a Promising Protective Antigen for Vaccination Against Acinetobacter baumannii

Capsular polysaccharide inhibits vaccine-induced O-antigen antibody binding and function across both classical and hypervirulent K2:O1 strains ofKlebsiella pneumoniae

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