Abstract
Acinetobacter baumannii (A. baumannii) is becoming a common global concern due to the emergence of multi-drug or pan-drug resistant strains. Confronting the issue of antimicrobial resistance by developing vaccines against the resistant pathogen is becoming a common strategy. In this study, different methods for preparing A. baumannii outer membrane vesicles (AbOMVs) vaccines were developed. sOMV (spontaneously released AbOMV) was extracted from the culture supernatant, while SuOMV (sucrose-extracted AbOMV) and nOMV (native AbOMV) were prepared from the bacterial cells. Three AbOMVs exhibited significant differences in yield, particle size, protein composition, and LPS/DNA content. To compare the protective efficacy of the three AbOMVs, groups of mice were immunized either intramuscularly or intranasally with each AbOMV. Vaccination via both routes conferred significant protection against lethal and sub-lethal A. baumannii challenge. Moreover, intranasal vaccination provided more robust protection, which may be attributed to the induction of significant sIgA response in mucosal sites. Among the three AbOMVs, SuOMV elicited the highest level of protective immunity against A. baumannii infection, whether intramuscular or intranasal immunization, which was characterized by the expression of the most profound specific serum IgG or mucosal sIgA. Taken together, the preparation method had a significant effect on the yield, morphology, and composition of AbOMVs, that further influenced the protective effect against A. baumannii infection.
Highlights
Acinetobacter baumannii (A. baumannii) is a gram-negative, aerobic bacterium, which is generally harmless to healthy individuals, but can cause serious infections such as ventilator-associated pneumonia, bloodstream infection, and wound infections in hospitalized, severely unwell patients on intensive care units [1,2,3]
The protein patterns of A. baumannii outer membrane vesicles (AbOMVs) prepared from different methods were firstly determined by SDS-PAGE
Total proteins in AbOMV were digested with trypsin and the compositions were further analyzed using a Linear Trap Quadropole (LTQ)-Orbitrap Velos Pro MS spectrometer (Tables S1–S3)
Summary
Acinetobacter baumannii (A. baumannii) is a gram-negative, aerobic bacterium, which is generally harmless to healthy individuals, but can cause serious infections such as ventilator-associated pneumonia, bloodstream infection, and wound infections in hospitalized, severely unwell patients on intensive care units [1,2,3]. Due to intrinsic or acquired resistance to a wide range of antibiotics, AbOMVs’ Preparation Method Impact Efficacy resulting in multidrug-resistant (MDR) or even pandrugresistant (PDR) strains [4], A. baumannii has emerged as one of the most challenging pathogens to effectively treat [5, 6]. The mortality rates associated with A. baumannii infection has reported to be 26.0–55.7% [7], and effective prevention or treatment procedures are urgently needed. Different kinds of vaccines have been formulated aiming at protecting against A. baumannii infection. Inactivated whole cells (IWC) [8], outer membrane complex (OMC) [9], outer membrane vesicles (OMVs) [10, 11], and several outer membrane proteins including OmpA [12], Omp22 [13], and OmpK [14] have been identified as vaccine candidates through active and passive immunizations of experimental animals
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