Active and Passive Immunization Protects against Lethal, Extreme Drug Resistant-Acinetobacter baumannii Infection

Abstract

Extreme-drug-resistant (XDR) Acinetobacter baumannii is a rapidly emerging pathogen causing infections with unacceptably high mortality rates due to inadequate available treatment. New methods to prevent and treat such infections are a critical unmet medical need. To conduct a rational vaccine discovery program, OmpA was identified as the primary target of humoral immune response after intravenous infection by A. baumannii in mice. OmpA was >99% conserved at the amino acid level across clinical isolates harvested between 1951 and 2009 from cerebrospinal fluid, blood, lung, and wound infections, including carbapenem-resistant isolates, and was ≥89% conserved among other sequenced strains, but had minimal homology to the human proteome. Vaccination of diabetic mice with recombinant OmpA (rOmpA) with aluminum hydroxide adjuvant markedly improved survival and reduced tissue bacterial burden in mice infected intravenously. Vaccination induced high titers of anti-OmpA antibodies, the levels of which correlated with survival in mice. Passive transfer with immune sera recapitulated protection. Immune sera did not enhance complement-mediated killing but did enhance opsonophagocytic killing of A. baumannii. These results define active and passive immunization strategies to prevent and treat highly lethal, XDR A. baumannii infections.

Evaluation of the Trimeric Autotransporter Ata as a Vaccine Candidate against Acinetobacter baumannii Infections

“…That study, while promising, had the limitation of the undefined nature of the vaccine preparations. Another study evaluated OmpA as a target for vaccination against extreme drug-resistant A. baumannii infections (22), but only a single A. baumannii strain was evaluated, which limits the interpretation of those findings.…”

Molecular analysis of AbOmpA type-1 as immunogenic target for therapeutic interventions against MDR Acinetobacter baumannii infection

“…Several studies have evaluated various vaccine candidates against A. baumannii infection [31]. Recently, AbOmpA has been considered as a potent vaccine candidate for protection against A.baumannii infections in diabetic mice models [32]. The results of our study showed that outer membrane protein A is widespread among the pathogenic members of Enterobacteriaceae and non-Enterobacteriaceae families such as A. baumannii.…”

Physiology and Pathology of Multidrug-Resistant Bacteria: Antibodies- and Vaccines-Based Pathogen-Specific Targeting

“…baumannii challenge; use of antibodies against OmpA also elicited similar protective efect on diabetic mice with lethal A. baumannii infection [168]. Interestingly, dosage of A. baumannii rOmpA vaccine correlates with various B cell epitopes and immunodominant T cell epitopes, emphasizing dosage needs to be taken into account for vaccine development [169].…”

“…OmpA can bind with host cell directly, internalize within mitochondria and nuclei compartments of host cell, and induce host cell death [165,166]. Moreover, OmpA is highly conserved within six clinical isolates (99% protein sequence identity) and 14 other NCBI GenBank deposited sequences from diferent isolates of A. baumannii (89% protein sequence identity), while OmpA shows no homology to human proteins [168].…”