Abstract
AbstarctAcinetobacter 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.
Highlights
Numerous vaccine candidates have been tested against this ubiquitous opportunistic pathogen
BamA is not characterized in A. baumannii but it is highly conserved among the Gram negative bacteria due to its crucial role in outer membrane protein assembly
Singh et al.[23] screened the whole proteome of A. baumannii and selected potential vaccine candidates by Vaxign online tool on the basis of criteria required for an ideal vaccine candidate protein such as their sub-cellular localization, number of trans-membrane helices, adhesion probability, ability to bind to MHCs and similarity with human and mouse proteomes
Summary
Numerous vaccine candidates have been tested against this ubiquitous opportunistic pathogen. Immunization with a putative pilus assembly protein, FilF18 and outer membrane nuclease[19] were found conferring partial protection against A. baumannii ATCC 19606 and controlled the infection by reducing bacterial load in organs and pro-inflammatory cytokine levels. BamA is not characterized in A. baumannii but it is highly conserved among the Gram negative bacteria due to its crucial role in outer membrane protein assembly. Outer membrane proteins act as effective protective antigens because they are capable of inducing host immune system and providing protection against bacterial challenge[16,17,18,19,21,22]. We showed that BamA is highly conserved in A. baumannii and has the ability to evoke immune response in mice leading to efficient immunoprotection
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