Over the past decade A. baumannii has emerged to become one of the most antibiotic-resistant causes of infections all over the world. It is critical that new strategies are developed to prevent and treat such infections. Therefore, a rational discovery program was undertaken to identify a candidate antigen for an A. baumannii-targeted vaccine. Antigen discovery was based on identification of the immunodominant targets from A. baumannii membrane protein preparations following systemic infection. rOmpA was identified as a promising candidate for active and passive immunization based on humoral immunodominance during infection in mice. OmpA was highly conserved across multiple clinical isolates, and shared minimal homology with the human proteome. Substantial efficacy was seen in lethal murine models in immunocompromised, diabetic mice when administered with Al(OH)3 adjuvant.
Individual mouse antibody titers correlated with survival and immune serum was effective during passive immunization. It has been previously reported that A. baumannii
can be resistant to complement-mediated killing 
, however the complement resistance in A. baumannii
appears to be strain dependent 
. In a previous study, complement susceptible strains were reported to decrease in quantity by 5 to 10-fold after 1 hour of incubation in serum, whereas resistant strains increased during that hour by a similar amount 
. In the current study, the A. baumannii
strains tested doubled or tripled after 1 hour of culture in the presence of serum (immune and non-immune), ruling out a direct complement-mediated effect. Hence, antibodies to OmpA did not overcome the innate resistance of the organism to complement-mediated killing. However, immune serum from vaccinated mice did enhance opsonophagocytic killing of the organism. Collectively, these results confirm that enhanced uptake and killing of A. baumannii
by antibody-based opsonophagocytosis lead to more effective clearance of A. baumannii
from tissue. Thus, phagocytic killing of A. baumannii
can be enhanced by antibodies targeting OmpA.
OmpA has been found to have a variety of interesting biological properties in in vitro
model systems. For example, OmpA has been shown to bind to eukaryotic cells, translocate to the nucleus, and induce cell death 
. Furthermore, OmpA binding to Factor H may be responsible for the resistance of A. baumannii
to complement-mediated killing 
. However, as mentioned, in the current study antibodies targeting OmpA did not overcome serum resistance of the organism. Rather, anti-OmpA antibodies enhanced opsonophagocytic killing of the organism.
Recently, a whole cell, killed A. baumannii
vaccine was described which protected mice from infection 
. The investigators prepared crude cell membrane protein preparations and found that the immunologically active components of the whole cell vaccine were found in the cell membrane 
. The crude membrane preparation contained at least 61 separate proteins, and the resulting mixture protected mice from lethal A. baumannii
infection. These results underscore the potential for A. baumannii
vaccines to be effective, and are complementary to the current study, which defines one antigen as a promising lead candidate to develop a recombinant protein based vaccine, as opposed to a crude cell membrane extract. In contrast to the previous study, which found that antibodies were raised against numerous antigens when a crude membrane preparation was used to immunize mice 
, the current study defined humoral immune response after iv infection with viable, pathogenic organisms, rather than immunization with membrane protein preparations. While OmpA was identified as a predominant protein target of humoral immunity after iv infection, the current results cannot exclude a broader immune response to other proteins as well.
In summary, rOmpA is a promising candidate for active and passive immunization to prevent XDR/PDR A. baumannii infections. Efficacy has been established at feasible doses with a translatable adjuvant. Use of the vaccine elucidated opsonophagocytic antibodies as the mechanism of adaptive host defense that protected against A. baumannii infection. Anti-OmpA antibody titer was identified as a surrogate marker of protection. These results underscore the translational potential of rOmpA as a target for active and passive immunization against this highly antibiotic-resistant, rapidly emerging pathogen.