Outer Membrane Protein, Oma87 Prevents Acinetobacter baumannii Infection

Abstract

Acinetobacter baumannii is one of the most problematic pathogens in clinical settings. Emerging of its antibiotic-resistant strains persuade researchers to find alternative treatment options such as immunization against the notorious nosocomial pathogen. Oma87 has been introduced as an immunogenic outer membrane protein via reverse vaccinology. However, protectivity of A. baumannii Oma87 is not well known. The current research undertakes a study on the immunogenicity of recombinant Oma87 in a murine model. Some physico-chemical properties were assessed via in silico analyses. The corresponding gene was amplified and cloned into pET28a plasmid. The recombinant protein was purified and then was administered to immunize mice. Sera obtained from the immunized mice were assessed with respect to the triggered antibodies. Challenges were performed on actively or passively immunized mice. In silico analyses revealed that this protein is the same as BamA. A high titer of specific antibody was raised against rOma87 even after the first injection. The specific antibody recognized the whole cell of A. baumannii. Both active and passive immunizations confer 100 and 50% protection, respectively against ~ 2 × lethal dose (LD) of A. baumannii in the murine sepsis model. Although none of mice received ~ 5 × LD of A. baumannii survived in passive immunization, 25% of mice challenged with ~ 7 × LD of the bacteria survived and the dead mice exhibited a delayed death. Based on these results, Oma87 is the same as BamA which could be considered as a promising vaccine candidate against A. baumannii in the sepsis model.

Recent Advances in the Pursuit of an Effective Acinetobacter baumannii Vaccine

“…This has been the case with Oma87 [ 101 ], the N-terminal region of Outer membrane porin F (OprF) [ 102 ], Omp22 [ 103 ], and OmpA [ 104 , 105 , 106 ]. Each of these outer membrane protein-based vaccines elicited a robust IgG response and increased the survival rates of mice compared to the naïve control mice [ 101 , 102 , 103 , 104 , 105 , 106 ]. OmpA was combined with the secreted serine protease PKF in an antigen cocktail and evaluated for protection against A. baumannii infection [ 107 ].…”

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

“…A. baumannii outer membrane holds scores of OMPs including OmpA, CarO, OprD- like OMPs, Omp 33-36 kDa, AbuO, TolB, DcaP, Oma87/BamA, NmRmpM, CadF, OprF, etc. ( Borneleit and Kleber, 1991 ; Park et al, 2012 ; Srinivasan et al, 2015 ; Lee et al, 2017 ; Bhamidimarri et al, 2019 ; Rasooli et al, 2020 ). OMPs participate in a wide range of functions that assist the bacterium in enduring the harsh environmental conditions, in combating the threat posed by antimicrobial compounds ( Limansky et al, 2002 ; del Mar Tomás et al, 2005 ; Dupont et al, 2005 ; Mussi et al, 2007 ; Choi et al, 2008a ; Srinivasan et al, 2015 ; Wang et al, 2015 ), host ( Choi et al, 2008b,c ; Lee et al, 2008 ; Gaddy, 2010 ), and surprisingly, in degrading crude oil ( Hanson et al, 1994 ).…”

“…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.…”

Designing Multi-Antigen Vaccines Against Acinetobacter baumannii Using Systemic Approaches

“…A monoclonal antibody against the A. baumannii capsular polysaccharide was able to rescue infected mice in a lethal sepsis model (12). Candidates that have been tested in preclinical vaccine models include the OmpA porin (13), Ata (14) and Bap (15), and more recently BamA (16) and Omp22 (17) among others (11). However, many of these candidates provide only partial protection against infection, as exemplified by vaccination with the OmpA porin (13).…”