P. aeruginosa Vaccine Development

P. aeruginosa Vaccine Development

Pseudomonas aeruginosa (P. aeruginosa) is a multifunctional opportunistic pathogen capable of causing acute and chronic infections. Pseudomonas aeruginosa infection is associated with high morbidity and mortality in many groups, including those with healthcare-associated pneumonia, chronic obstructive pulmonary disease (COPD), or cystic fibrosis (CF). Its enormous adaptive capacity stems from the large number of variable virulence factors and antibiotic resistance determinants harbored in its genome.

Representation of P. aeruginosa adaptation to the (CF) lung over the course of infection. (Jurado-Martín I, et al.,2021)

P. aeruginosa Vaccine

As an important soil bacterium, P. aeruginosa is able to decompose PAHs and is frequently detected in reservoirs contaminated by animals and humans, such as sewage and water tanks inside and outside hospitals. P. aeruginosa can cause widespread infection in hospitalized and immunocompromised patients, burns, surgical wounds, and CF patients. In addition, with increasing drug resistance, there is an urgent need to develop methods to prevent P. aeruginosa infection, such as vaccine development. Although there have been many studies on the development of P. aeruginosa vaccines, no vaccines are currently approved for clinical use.

The particulate nature and multivalent structure of virus-like particles (VLPs) enable them to elicit robust immune responses in vivo and make them effective scaffolds for the display of heterologous antigens in a highly immunogenic form. The VLP vaccine production platform enables the development of effective vaccines against P. aeruginosa.

Virulence Factors for P. aeruginosa Vaccine Development

The virulence factors of P. aeruginosa include lipopolysaccharides (LPS), outer membrane proteins (OMP), extracellular proteins, flagella, fimbriae, exotoxins, etc., which can be used as antigens of Pseudomonas aeruginosa for vaccine development.

• LPS
  LPS consists of three domains: lipid A, the core region, and the O-antigen or O-polysaccharide (OPS), which constitute a physical barrier that mediates the interaction of Pseudomonas aeruginosa with host receptors. LPS has endotoxin activity that can cause tissue damage.
• OMP
  The outer membrane proteins of P. aeruginosa include OprF, OprH, and OprD, which play different roles in P. aeruginosa infection.
  OprF, the major porin, is the most abundant non-lipoprotein OMP and is essential for P. aeruginosa, contributing to the extremely low permeability of the outer membrane (OM) and maintaining OM integrity.
  OprH is involved in antibiotic resistance to aminoglycosides and polymyxins and promotes OM integrity by interacting with LPS.
  OprD is involved in the entry of carbapenems and the transport of basic amino acids, polypeptides and gluconate.
• Lipoproteins
  Lipoproteins are part of the OM biochemical assembly machinery and are able to interact with peptidoglycans that maintain cellular integrity, protect cells from oxidative stress, and participate in the excretion of harmful molecules including antibiotic drugs, thereby conferring antibiotic resistance.
• Flagellum
  P. aeruginosa has unipolar flagella, which are mainly responsible for generating the force that moves the bacteria forward.
• Type IV Pili
  Type IV fimbriae are retractable, hair-like filamentous appendages. Basic structure for initiating infection by mediating P. aeruginosa motility and adhesion.

Main virulence factors of P. aeruginosa. (Jurado-Martín I, et al., 2021)

How We Can Help

As an expert in building VLPs from VLPlant^TM platform, CD BioSciences uses its expertise to help our clients develop P. aeruginosa vaccines. We are good at customizing our services according to the needs of our clients. Please contact us if you are interested.

Reference

1. Jurado-Martín I.; et al., Pseudomonas aeruginosa: An Audacious Pathogen with an Adaptable Arsenal of Virulence Factors. Int J Mol Sci. 2021, 22: 3128-3162.