Development and Evaluation of an Immunoinformatics-Based Multi-Peptide Vaccine against Acinetobacter baumannii Infection.

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 into Acinetobacter baumannii protective immunity.

Acinetobacter baumannii is a nosocomic opportunistic Gram-negative bacteria known for its extensive drug-resistant phenotype. A. baumannii hospital-acquired infections are major contributors to increased costs and mortality observed during the COVID-19 pandemic. With few effective antimicrobials available for treatment of this pathogen, immune-based therapy becomes an attractive strategy to combat multi-drug resistant Acinetobacter infection. Immunotherapeutics is a field of growing interest with advances in vaccines and monoclonal antibodies providing insight into the protective immune response required to successfully combat this pathogen. This review focuses on current knowledge describing the adaptive immune response to A. baumannii, the importance of antibody-mediated protection, developments in cell-mediated protection, and their respective therapeutic application going forward. With A. baumannii's increasing resistance to most current antimicrobials, elucidating an effective host adaptive immune response is paramount in the guidance of future immunotherapeutic development.