Evaluation of a polypeptide vaccine against Acinetobacter infection

Abstract Acinetobacter baumannii (Ab) is a Gram-negative bacterium emerging as a major cause of nosocomial infections. The most frequent clinical manifestations of Ab infection are ventilator-associated pneumonia and catheter-related bloodstream/urinary infection, in addition to that of wounds. The rapid emergence of its multidrug resistant phenotype makes Ab infection increasingly difficulty to treat, thus, there is a timely need to develop a nonantibiotics-based intervention, e.g., vaccination, to control this bacterial disease. The goal of this proposal is to further address the current gaps associated with Acinetobacter vaccine development by (1) assessing the efficacy of novel chimeric polypeptide vaccines, (2) identifying potential immune correlates that can be used as protective biomarkers and efficacy indicators for future vaccine development. Specifically, individual peptides containing both T cell and B cell epitopes in our previously constructed protective Acinetobacter Multi-Epitope Vaccines (AMEV1 and AMEV2), will be characterized for their immunogenicity and down selected to construct a refined vaccine, AMEV3, for improved protection against pulmonary Acinetobacter infection. The AMEV3- mediated protection will be characterized by assessing survival rates, reduction of bacterial burdens, and preventing pathology in conventional C57BL/6 and humanized HLA-DR4 transgenic mice. Furthermore, the protective role of antibodies generated by AMEV3 immunization will be studied by assessing passive immunization efficacy, serum bactericidal activity, and enhancement of opsonophagocytic killing. Results of this proposed study will advance our scientific knowledge of developing multivalent B/T epitope subunit vaccines and gain insight into the protective mechanisms of immune sera against Ab infection.