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Aim: Acinetobacter baumannii, an increasingly serious health threat, is considered as one of the six most dangerous microbes of high mortality rate. However, treatment of its infections is difficult because of the lack of efficient antibiotic or commercial vaccines. Passive immunization through administration of specific antibodies such as IgY, could be an attractive practical solution. Methods and Results: In the current study, antigenicity of two recombinant outer membrane proteins (OmpA and Omp34) as well as inactivated whole cell of A. baumannii was assessed by ELISA. Moreover, prophylactic effects of specific IgY antibodies (avian antibody) raised against these antigens were evaluated in a murine pneumonia model. The specific IgY antibodies had various prophylactic effects in the pneumonia model. OmpA was the most potent antigen in terms of triggering antibody and conferring protection. While a synergic effect was observed in ELISA for antibodies raised against a combination of OmpA and Omp34 (which are known as Omp33-36 and Omp34 kDa), an antagonistic effect was unexpectedly seen in challenges. The reason for this phenomenon remains to be precisely addressed. Conclusion: All the specific IgY antibodies could protect mice against pneumonia caused by A. baumannii. Significance and Impact of the Study: The specific IgY antibodies could be employed as a pharmaceutical against pneumonia caused by A. baumannii. emergence of highly antibiotic-resistant strains including multidrug-resistant (MDR) and pan-drug-resistant strains (Wang et al. 2003;Dijkshoorn et al. 2007;Pach on and McConnell 2014). In spite of the increasing prevalence of MDR strains and their high mortality, an efficient antibiotic is not provided by the pharmaceutical industry for the treatment of its infections (Pach on and McConnell 2014). These implications highlight active and passive immunizations as cost-effective approaches to reduce the clinical and economic burden of infections caused by this notorious pathogen (Ahmad et al. 2016).

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Acinetobacter baumannii is an important human pathogen causing substantial mortality in hospitalized patients for which treatment with antibiotics has become problematic due to growing antibiotic resistance. In an attempt to develop alternative strategies for dealing with these serious infections surface antigens are being considered as targets for vaccines or immunotherapy. The surface receptor proteins required for zinc acquisition in Gram-negative bacterial pathogens have been proposed as vaccine targets due to their crucial role for growth in the human host. In this study we selected the putative ZnuD outer membrane receptor from A. baumannii as a target for vaccine development. Due to challenges in production of an integral outer membrane protein for vaccine production, we adopted a recently described hybrid antigen approach in which surface epitopes from the Neisseria meningitidis TbpA receptor protein were displayed on a derivative of the C-lobe of the surface lipoprotein TbpB, named the loopless C-lobe (LCL). A structural model for ZnuD was generated and four surface loops were selected for hybrid antigen production by computational approaches. Hybrid antigens were designed displaying the four selected loops (2, 5, 7, and 11) individually or together in a single hybrid antigen. The hybrid antigens along with ZnuD and the LCL scaffold were produced in the E. coli cytoplasm either as soluble antigens or as inclusion bodies, that were used to generate soluble antigens upon refolding. Mice were immunized with the hybrid antigens, ZnuD or LCL and then used in an A. baumannii sepsis model to evaluate their ability to protect against infection. As expected, the LCL scaffold did not induce a protective immune response, enabling us to attribute observed protection to the displayed loops. Immunization with the refolded ZnuD protein protected 63% of the mice while immunization with hybrid antigens displaying individual loops achieved between 25 and 50% protection. Notably, the mice immunized with the hybrid antigen displaying the four loops were completely protected from infection.

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