Assessing Antibody-Mediated Protection Against Acinetobacter baumannii Infection Induced by Multi-Epitope Vaccines AMEV2 & AMEV7 2335246

Abstract

Abstract Introduction Acinetobacter baumannii (Ab) is an increasingly multi-drug resistant (MDR) nosocomial pathogen. Due to limited antibiotic options, there is an urgent need to develop alternative or adjunct treatments such as immune-based therapeutics against Ab. Methods Two novel subunit vaccines, Acinetobacter Multi-Epitope Vaccine (AMEV) 2 & 7, were developed against Ab using immunoinformatics. Passive immunization and opsonophagocytic killing assays (OPKAs) were used to assess the antibody-mediated immune protection of AMEV2 and AMEV7 against Ab. Results We identified 5 antigenic peptides containing both putative B- and T-cell epitopes from proteins associated with Ab pathogenesis to construct two multi-epitope vaccines. AMEV2 was constructed with all 5 peptides in tandem while AMEV7 contained 3 copies of the characterized protective peptide, pTonB. All 5 peptides reacted strongly to the antisera from Ab-infected mice validating their antigenicity. Subcutaneous vaccination with AMEV2 and AMEV7 protected mice against pulmonary and systemic challenge, respectively, with a hypervirulent Ab clinical isolate. AMEV vaccines improved survival rates by 40-60% and reduced organ Ab burden by 1-2 logs. Passive immunization with AMEV2 immune sera protected 66.7% of mice against pulmonary Ab infection, while only 16.7% of mice received nonimmune sera were protected. While AMEV2 sera did not demonstrate complement-mediated direct Ab killing, the immune sera did enhance killing of Ab in the presence of primary bone marrow-derived macrophages. This opsonophagocytic killing was mediated by Fc receptor and complement fixation. Conclusion We have shown that protection afforded by AMEV2 is antibody-based, acting through opsonophagocytic killing. While we hypothesize AMEV7 has a similar mechanism, further analysis will be performed to confirm. Together, our studies highlight the importance of antibody-mediated protection and broaden the possibilities of immune therapies against this MDR pathogen. Funding Source NIH R21 Topic Categories Vaccines and Immunotherapy (VAC)