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Updated: May 13, 2026
Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
Generation and Evaluation of a Multi-Epitope Vaccine Against Acinetobacter baumannii, a Nosocomial Bacterial Pathogen
Nicolas D Prather1, Jadelynn Aki1, Sean Jeffreys1
1Department of Molecular Microbiology and Immunology, University of Texas at San Antonio, San Antonio, TX 78249, USA.
Background/Objectives:
Multidrug-resistant (MDR) Acinetobacter baumannii (Ab) has emerged as a significant bacterial pathogen responsible for nosocomial infections. The most common clinical manifestations of Ab infection include ventilator-associated pneumonia and catheter-related bloodstream/urinary infections. Given the extensive MDR phenotype of Ab, preventive vaccination strategies are crucial for protecting susceptible populations.
Methods:
We utilized immunoinformatics to identify candidate peptides containing both putative B- and T-cell epitopes from proteins associated with Ab pathogenesis. Subsequently, we designed novel Acinetobacter Multi-Epitope Vaccines (AMEVs), each comprising an Ab thioredoxin A (TrxA) leader protein, five to seven of the identified peptide antigens, and a C-terminal His(6x)-tag to facilitate protein purification.
Results:
Subcutaneous vaccination of C57BL/6 mice with AMEV1 or AMEV2, formulated with TiterMax adjuvant, conferred 60% and 80% protection, respectively, against intraperitoneal Ab challenge. AMEV vaccination induced a robust antibody response to each corresponding whole protein and most of its component peptides. We then constructed an improved vaccine, AMEV5, which included the Ab TrxA protein and seven confirmed B-cell epitope peptides. Subcutaneous immunization of BALB/c mice (n = 10 per group) with rAMEV5 emulsified in Adda03 adjuvant activated antigen-specific IL-5-secreting T cells and antibody-producing B cells. Evaluation of vaccine efficacy demonstrated that AMEV2- and AMEV5-immunized mice were protected from a lethal intraperitoneal Ab challenge, with survival rates of 70% and 90%, respectively.
Conclusions:
These study results provide insights into the application of reverse vaccinology to combat the rise of MDR Acinetobacter infection.
Insights
Novel multi-epitope vaccines (AMEVs) targeting multidrug-resistant Acinetobacter baumannii demonstrated significant protection in mice. These AMEVs offer a promising strategy against challenging nosocomial infections.
Area of Science:
- Microbiology
- Immunology
- Vaccine Development
Background:
- Multidrug-resistant Acinetobacter baumannii (MDR Ab) is a major cause of hospital-acquired infections.
- Infections include ventilator-associated pneumonia and catheter-related bloodstream/urinary infections.
- Preventive vaccination is crucial due to extensive MDR phenotypes.
Purpose of the Study:
- To identify peptide antigens for vaccine development against MDR Ab using immunoinformatics.
- To design and evaluate novel Acinetobacter Multi-Epitope Vaccines (AMEVs).
Main Methods:
- Immunoinformatics identified B- and T-cell epitopes from Ab pathogenesis proteins.
- Designed AMEVs containing Ab thioredoxin A (TrxA) leader, peptide antigens, and His-tag.
- Vaccine efficacy tested in mouse models (C57BL/6 and BALB/c) with different adjuvants.
Main Results:
- AMEV1 and AMEV2 conferred 60% and 80% protection against Ab challenge in mice.
- Vaccination induced robust antibody responses to whole proteins and peptides.
- Improved vaccine AMEV5 showed 90% survival in mice against lethal Ab challenge, activating T and B cells.
Conclusions:
- Reverse vaccinology approach successfully developed effective AMEVs against MDR Ab.
- Vaccine candidates show promise in combating nosocomial infections caused by MDR Ab.
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