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Development of a nano-emulsion based multivalent protein subunit vaccine against Pseudomonas aeruginosa
Debaki R Howlader1,2,3, Rahul Shubhra Mandal4, Ti Lu1,2,3
1Department of Veterinary Pathobiology, Center for Veterinary Medicine, University of Missouri, Columbia, MO, United States.
Insights
A new bivalent vaccine targeting Pseudomonas aeruginosa (Pa) shows promise for protecting elderly individuals. This intranasal vaccine elicits a T cell response against drug-resistant bacterial strains.
Area of Science:
- Bacteriology
- Immunology
- Vaccinology
Background:
- Pseudomonas aeruginosa (Pa) causes severe hospital-acquired infections, particularly in immunocompromised and elderly individuals.
- Increasing drug resistance and lack of broad-spectrum vaccines against T3SA+ and ExlA+/T3SA- Pa strains pose significant public health challenges.
- Elderly populations are more susceptible to severe Pa disease, necessitating targeted prophylactic strategies.
Purpose of the Study:
- To formulate and evaluate a novel bivalent subunit vaccine against both T3SA+ and ExlA+ Pseudomonas aeruginosa strains.
- To assess the vaccine's immunogenicity and protective efficacy in young and elderly mice, mimicking human age-related susceptibility.
- To investigate the immune response elicited by the vaccine, focusing on T cell-mediated adaptive immunity.
Main Methods:
- A bivalent vaccine (ExlA/L-PaF/BECC/ME) was created by combining the ExlA moiety with a T3SA-based platform (L-PaF) in an emulsion with BECC438b (TLR4 agonist).
- The vaccine was administered intranasally to young and elderly mice.
- Mice were subsequently infected with Pa, and immune responses, including T cell-mediated adaptive immunity, were analyzed.
Main Results:
- Mice immunized with the ExlA/L-PaF/BECC/ME vaccine demonstrated a T cell-mediated adaptive immune response post-Pa infection.
- In contrast, control mice vaccinated with PBS exhibited a rapid inflammatory response.
- The study identified key genes and pathways involved in generating an anti-Pa immune response.
Conclusions:
- The developed bivalent subunit vaccine (ExlA/L-PaF/BECC/ME) is a promising candidate for protecting against Pseudomonas aeruginosa infections.
- The vaccine formulation shows potential for inducing protective immunity, particularly in elderly individuals who are more vulnerable to severe Pa disease.
- Intranasal administration and the inclusion of ExlA and T3SA components contribute to a robust anti-Pa immune response.
Abstract:
Pseudomonas aeruginosa (Pa) is an opportunistic bacterial pathogen responsible for severe hospital acquired infections in immunocompromised and elderly individuals. Emergence of increasingly drug resistant strains and the absence of a broad-spectrum prophylactic vaccine against both T3SA+ (type III secretion apparatus) and ExlA+/T3SA- Pa strains worsen the situation in a post-pandemic world. Thus, we formulated a candidate subunit vaccine (called ExlA/L-PaF/BECC/ME) against both Pa types. This bivalent vaccine was generated by combining the C-terminal active moiety of exolysin A (ExlA) produced by non-T3SA Pa strains with our T3SA-based vaccine platform, L-PaF, in an oil-in-water emulsion. The ExlA/L-PaF in ME (MedImmune emulsion) was then mixed with BECC438b, an engineered lipid A analogue and a TLR4 agonist. This formulation was administered intranasally (IN) to young and elderly mice to determine its potency across a diverse age-range. The elderly mice were used to mimic the infection seen in elderly humans, who are more susceptible to serious Pa disease compared to their young adult counterparts. After Pa infection, mice immunized with ExlA/L-PaF/BECC/ME displayed a T cell-mediated adaptive response while PBS-vaccinated mice experienced a rapid onset inflammatory response. Important genes and pathways were observed, which give rise to an anti-Pa immune response. Thus, this vaccine has the potential to protect aged individuals in our population from serious Pa infection.
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