Immunoprotective potential of BamA, the outer membrane protein assembly factor, against MDR Acinetobacter baumannii

Abstract

Abstarct Acinetobacter baumannii infections are responsible for major health problems in immunocompromised patients particularly in intensive care units. Due to rapid acquisition of and also inherent drug resistance, a vaccine is an effective treatment option against this pathogen. BamA, an outer membrane β-barrel assembly protein, was identified in A. baumannii as potential vaccine candidate by in silico analysis. The immunoprotective efficacy of this highly conserved protein was investigated against a virulent multidrug resistant clinical isolate using murine pneumonia model. Recombinant BamA elicited a high IgG antibody titer (160000) in mice. Opsonophagocytic killing assay showed non-neutrilizing, opsonizing antibodies with combinatorial bactericidal activity of antibodies and complement components. Active and passive immunization protected 80 and 60% mice respectively against intranasal challenge with lethal dose (109 CFU) of virulent A. baumannii along with efficient clearance of bacteria in mice lungs and reduction in levels of pro-inflammatory cytokines viz. TNF-α, IL-6 and IL-1β in sera and lung tissue homogenate. Increase in levels of IL-10, an anti-inflammatory cytokine and reduction of neutrophils in lungs facilitated the control of infection. This study demonstrates the potential of BamA as effective vaccine candidate and a promising target for antibody-based therapy to protect against MDR A. baumannii infections.

Protective potentials of a siderophore receptor against Acinetobacter baumannii infections

“…In this study, partial protection against A. baumannii lethal dose was achieved in passively immunized mice. Antisera against single recombinant proteins in the previous studies induced relative to complete protection [7-9, 15,40]. In the current study, the survival rate was higher against A. baumannii ATCC 19606 compared to clinical isolate, ABI022.…”

“…Vaccination would be a proper solution to reduce the clinical and economic load of infections caused by A. baumannii. In this regard, various virulence factors of A. baumannii including capsular polysaccharide, biofilm associated protein (Bap), Acinetobacter trimeric autotransporter (Ata), OmpA, Omp22, OmpW, BauA, FilF, NucAb, BamA, SmpA, PLD as well as inactivated or attenuated whole cell, outer membrane complexes (OMCs) and outer membrane vesicles (OMVs) have been examined [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. However, there is no safe and effective vaccine for human use.…”

“…These receptors are crucial to full pathogenicity of A. baumannii [19]. It seems that antibody production develops a proper immunity to restrict A. baumannii infections [14,15]. Therefore, as the accessibility of antigenic target to interact with antibodies is an important issue, outer membrane proteins (OMPs) are of interest as vaccine targets [23].…”

The Outer Membrane Proteins OmpA, CarO, and OprD of Acinetobacter baumannii Confer a Two-Pronged Defense in Facilitating Its Success as a Potent Human Pathogen

“…In silico exploration into the genome of A. baumannii revealed a nuclease (NucAb), BamA (Oma87), FilF, and TolB in the outer membrane as potential vaccine targets. Immunization with these recombinant proteins protected mice from lethal challenge with A. baumannii ( Singh et al, 2014 , 2016 and Singh et al, 2017 ; Garg et al, 2016 ; Song et al, 2018 ; Rasooli et al, 2020 ). In another effort toward developing a subunit vaccine against A. baumannii infections, a fusion protein of OmpK and Omp22 was synthesized which provided significantly greater protection against A. baumannii challenge in mice than those immunized with either of the two proteins individually ( Huang et al, 2016 ; Guo et al, 2017 ; Guo S.J.…”

A Multi-epitope Peptide rOmp22 Encapsulated in Chitosan-PLGA Nanoparticles as Vaccine Candidate Against Acinetobacter baumannii Infection

“…Conventional vaccines developed from live attenuated or inactivated whole cells could induce strong humoral and cellular immunity, however, the clinical applications of such vaccines have been limited due to their complex compositions and potential safety concerns [8][9][10]. During the last decades, the research of vaccines against A. baumannii has primarily focused on various forms of recombinant antigens, including bio lm-associated protein Bap [11], auto-transporter (Ata) [12], outer membrane protein A (OmpA) [13], outer membrane protein assembly factor (BamA) [14], Poly-N-acetyl-β-(1-6)-glucosamine (PNAG) [15], and outer membrane protein 22 (Omp22) [16]. Animal studies showed that some single recombinant protein based vaccines provided only weak protection against A. baumannii infection or poor cross-protection against certain strains [17].…”