Bacterial Ghosts of Pseudomonas aeruginosa as a Promising Candidate Vaccine and Its Application in Diabetic Rats
Salah A Sheweita1,2, Amro A Amara3, Heba Gamal2
1Department of Clinical Biochemistry, Faculty of Medicine, King Khalid University, Abha 62529, Saudi Arabia.
Abstract:
Infections with Pseudomonas aeruginosa (PA) pose a major clinical threat worldwide especially to immunocompromised patients. As a novel vaccine network for many kinds of bacteria, bacterial ghosts (BGs) have recently been introduced. In the present research, using Sponge-Like Reduced Protocol, P. aeruginosa ghosts (PAGs) were prepared to maintain surface antigens and immunogenicity. This is the first study, to our knowledge, on the production of chemically induced well-structured bacterial ghosts for PA using concentrations of different chemicals. The research was carried out using diabetic rats who were orally immunized at two-week intervals with three doses of PAGs. Rats were subsequently challenged either by the oral route or by the model of ulcer infection with PA. In challenged rats, in addition to other immunological parameters, organ bioburden and wound healing were determined, respectively. Examination of the scanning and transmission electron microscope (EM) proved that PAGs with a proper three-dimensional structure were obtained. In contrast to control groups, oral PAGs promoted the generation of agglutinating antibodies, the development of IFN-γ, and the increase in phagocytic activity in vaccinated groups. Antibodies of the elicited PAGs were reactive to PA proteins and lipopolysaccharides. The defense against the PA challenge was observed in PAGs-immunized diabetic rats. The resulting PAGs in orally vaccinated diabetic rats were able to evoke unique humoral and cell-mediated immune responses and to defend them from the threat of skin wound infection. These results have positive implications for future studies on the PA vaccine.
Insights
This study developed chemically induced Pseudomonas aeruginosa ghosts (PAGs) as a novel oral vaccine. PAGs successfully evoked immune responses and protected diabetic rats against P. aeruginosa infection, showing promise for future vaccine development.
Area of Science:
- Microbiology
- Immunology
- Vaccine Development
Background:
- Pseudomonas aeruginosa (PA) infections are a significant global health concern, particularly for immunocompromised individuals.
- Bacterial ghosts (BGs) represent a novel vaccine platform with potential for broad bacterial applications.
- Developing effective vaccines against PA remains a critical unmet medical need.
Purpose of the Study:
- To prepare chemically induced, well-structured Pseudomonas aeruginosa ghosts (PAGs) using a novel protocol.
- To evaluate the immunogenicity and protective efficacy of orally administered PAGs in a diabetic rat model.
- To investigate the humoral and cell-mediated immune responses induced by PAGs.
Main Methods:
- PAGs were produced using a Sponge-Like Reduced Protocol with varying chemical concentrations.
- Diabetic rats received three oral doses of PAGs at two-week intervals.
- Immunized rats were challenged with PA via oral or ulcer infection models, with immunological parameters, organ bioburden, and wound healing assessed.
Main Results:
- Electron microscopy confirmed the successful preparation of well-structured PAGs.
- Oral PAG vaccination stimulated agglutinating antibodies, IFN-γ production, and enhanced phagocytic activity compared to controls.
- Elicited antibodies showed reactivity to PA proteins and lipopolysaccharides.
- PAG-immunized rats demonstrated significant defense against PA challenge, including improved wound healing.
Conclusions:
- Chemically induced PAGs are a viable candidate for an oral vaccine against Pseudomonas aeruginosa.
- Oral vaccination with PAGs effectively elicits both humoral and cell-mediated immunity in diabetic rats.
- The study demonstrates the potential of PAGs to protect against PA infection, particularly in challenging models like skin wound infections.
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