Development and Evaluation of an Immunoinformatics-Based Multi-Peptide Vaccine against Acinetobacter baumannii
Sean Jeffreys1, Megan P Tompkins1, Jadelynn Aki1
1Department of Molecular Microbiology and Immunology, University of Texas at San Antonio, San Antonio, TX 78249, USA.
Abstract:
Multi-drug-resistant (MDR) Acinetobacter baumannii is an opportunistic pathogen associated with hospital-acquired infections. Due to its environmental persistence, virulence, and limited treatment options, this organism causes both increased patient mortality and incurred healthcare costs. Thus, prophylactic vaccination could be ideal for intervention against MDR Acinetobacter infection in susceptible populations. In this study, we employed immunoinformatics to identify peptides containing both putative B- and T-cell epitopes from proteins associated with A. baumannii pathogenesis. A novel Acinetobacter Multi-Epitope Vaccine (AMEV2) was constructed using an A. baumannii thioredoxin A (TrxA) leading protein sequence followed by five identified peptide antigens. Antisera from A. baumannii infected mice demonstrated reactivity to rAMEV2, and subcutaneous immunization of mice with rAMEV2 produced high antibody titer against the construct as well as peptide components. Immunization results in increased frequency of IL-4-secreting splenocytes indicative of a Th2 response. AMEV2-immunized mice were protected against intranasal challenge with a hypervirulent strain of A. baumannii and demonstrated reduced bacterial burden at 48 h. In contrast, all mock vaccinated mice succumbed to infection within 3 days. Results presented here provide insight into the effectiveness of immunoinformatic-based vaccine design and its potential as an effective strategy to combat the rise of MDR pathogens.
Insights
A novel vaccine, AMEV2, was designed using immunoinformatics to target multi-drug-resistant Acinetobacter baumannii. Vaccinated mice showed protection against infection, highlighting a promising strategy against this dangerous pathogen.
Area of Science:
- Infectious Diseases
- Vaccinology
- Immunology
- Bioinformatics
Background:
- Multi-drug-resistant (MDR) Acinetobacter baumannii is a significant cause of hospital-acquired infections.
- Its environmental persistence, virulence, and limited treatment options lead to high mortality and healthcare costs.
- Prophylactic vaccination presents an ideal intervention strategy for susceptible populations.
Purpose of the Study:
- To design and evaluate a novel multi-epitope vaccine against MDR Acinetobacter baumannii using immunoinformatics.
- To assess the immunogenicity and protective efficacy of the developed vaccine in a mouse model.
Main Methods:
- Immunoinformatics was used to identify B- and T-cell epitopes from A. baumannii virulence proteins.
- A multi-epitope vaccine construct (AMEV2) was designed, comprising A. baumannii thioredoxin A and five peptide antigens.
- The vaccine's immunogenicity and protective effects were evaluated in mice through immunization and challenge studies.
Main Results:
- Antisera from infected mice reacted with the recombinant AMEV2 (rAMEV2).
- Immunization with rAMEV2 induced high antibody titers and a Th2 immune response (increased IL-4 secreting splenocytes).
- AMEV2-immunized mice were protected against lethal intranasal challenge with a hypervirulent A. baumannii strain, showing reduced bacterial burden.
Conclusions:
- Immunoinformatics is an effective approach for designing vaccines against challenging pathogens.
- The developed AMEV2 vaccine demonstrated significant immunogenicity and protective efficacy against MDR Acinetobacter baumannii.
- This study provides a promising vaccine strategy to combat the rise of MDR pathogens.
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