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Review
. 2020 Dec 5;9(12):2617.
doi: 10.3390/cells9122617.

Understanding Pseudomonas aeruginosa-Host Interactions: The Ongoing Quest for an Efficacious Vaccine

Maite Sainz-Mejías  1 , Irene Jurado-Martín  1 , Siobhán McClean  1
Affiliations
Review

Understanding Pseudomonas aeruginosa-Host Interactions: The Ongoing Quest for an Efficacious Vaccine

Maite Sainz-Mejías et al. Cells. .

Abstract

Pseudomonas aeruginosa is a leading cause of chronic respiratory infections in people with cystic fibrosis (CF), bronchiectasis or chronic obstructive pulmonary disease (COPD), and acute infections in immunocompromised individuals. The adaptability of this opportunistic pathogen has hampered the development of antimicrobial therapies, and consequently, it remains a major threat to public health. Due to its antimicrobial resistance, vaccines represent an alternative strategy to tackle the pathogen, yet despite over 50 years of research on anti-Pseudomonas vaccines, no vaccine has been licensed. Nevertheless, there have been many advances in this field, including a better understanding of the host immune response and the biology of P. aeruginosa. Multiple antigens and adjuvants have been investigated with varying results. Although the most effective protective response remains to be established, it is clear that a polarised Th2 response is sub-optimal, and a mixed Th1/Th2 or Th1/Th17 response appears beneficial. This comprehensive review collates the current understanding of the complexities of P. aeruginosa-host interactions and its implication in vaccine design, with a view to understanding the current state of Pseudomonal vaccine development and the direction of future efforts. It highlights the importance of the incorporation of appropriate adjuvants to the protective antigen to yield optimal protection.

Keywords: ESKAPE; Pseudomonas aeruginosa; adjuvants; host-pathogen interactions; immune response; vaccine antigens; virulence factors.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the writing of the manuscript, or in the content of the review.

Figures

Figure 1
Figure 1
The main P. aeruginosa virulence factors involved in pathogenesis during pulmonary infections. The components highlighted with syringes have already been evaluated as vaccine antigens.
Figure 2
Figure 2
Host immune response against P. aeruginosa infections in the pseudostratified respiratory epithelium. (a) Recognition of P. aeruginosa. Pathogen recognition receptors (PRRs) located on the immune cells (TLR2, TLR4, TLR5, TLR9) recognise the PAMPs of P. aeruginosa (Lipoprotein, LPS, flagellin, and CpG-DNA, respectively) and trigger the production of pro-inflammatory cytokines and chemokines. OMV endocytosis activates the NF-κB pathway. (b) Innate immune response. (i) Neutrophils, recruited in response to P. aeruginosa (ii) Macrophages, which phagocytise bacteria or dying neutrophils (iii) complement system (CS). (c) Adaptive immune response. A skewed Th2 response occurs during P. aeruginosa infection with high but inefficient antibody production. In addition, the production of sIgA seems to be relevant, as its levels may correlate with the status of Pseudomonas infection.
Figure 3
Figure 3
Progress in the development of a vaccine against P. aeruginosa infections. The darker the colour of bar, the further the vaccine candidate was evaluated.
See this image and copyright information in PMC

References

    1. Azam M.W., Khan A.U. Updates on the pathogenicity status of Pseudomonas aeruginosa. Drug Discov. Today. 2019;24:350–359. doi: 10.1016/j.drudis.2018.07.003. - DOI - PubMed
    1. Bianconi I., Jeukens J., Freschi L., Alcalá-Franco B., Facchini M., Boyle B., Molinaro A., Kukavica-Ibrulj I., Tümmler B., Levesque R.C., et al. Comparative genomics and biological characterization of sequential Pseudomonas aeruginosa isolates from persistent airways infection. BMC Genom. 2015;16:1105. doi: 10.1186/s12864-015-2276-8. - DOI - PMC - PubMed
    1. Tümmler B. Emerging therapies against infections with Pseudomonas aeruginosa. F1000Res. 2019;8 doi: 10.12688/f1000research.19509.1. - DOI - PMC - PubMed
    1. Huang W., Hamouche J.E., Wang G., Smith M., Yin C., Dhand A., Dimitrova N., Fallon J.T. Integrated Genome-Wide Analysis of an Isogenic Pair of Pseudomonas aeruginosa Clinical Isolates with Differential Antimicrobial Resistance to Ceftolozane/Tazobactam, Ceftazidime/Avibactam, and Piperacillin/Tazobactam. Int. J. Mol. Sci. 2020;21:1026. doi: 10.3390/ijms21031026. - DOI - PMC - PubMed
    1. Center for Disease Control and Prevention (USA) Antibiotic Resistance Threats in the United States. [(accessed on 10 August 2020)];2019 Available online: https://www.cdc.gov/drugresistance/biggest-threats.html.

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