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Acinetobacter baumannii , a nosocomial pathogen, is considered as a common cause of hospital and community-acquired infections. Emerging multidrug-resistance in this pathogen followed by subsequent problems in treatment has been increasing to alarming levels that warrant investigation of new therapeutic approaches. One strategy to reduce antibiotic resistance is to use of vaccines. Although there is no vaccine currently in development for this pathogen, different attempts have been made to develop one. In this study, we used two different recombinant pilus proteins (CsuA/B and FimA) either singly or in combination to evaluate protective efficacy against A. baumannii in lethal and sub-lethal murine sepsis models. Active immunization with recombinant proteins in combination elicited high levels of IgG antibody after the first immunization and provided 62% (five of eight mice; p < 0·001) protection against a lethal dose (1·2 × 106 CFU) of A. baumannii along with efficient clearance of bacteria in internal organs viz. spleen, liver, and lungs at sub-lethal challenge. Immunization with CsuA/B alone conferred partial protection as demonstrated by low survival rate (three [37%] of eight mice; p < 0·05) after lethal challenge and reduction of bacteria in internal organs of the mice after 24 h post-sub-lethal infection. Immunization with FimA, in comparison to CsuA/B, showed better protection (four [50%] of eight mice; p < 0·01) and reduction in CFU after 14 h. Our results showed that pilus proteins in combination as a single immunogen could potentially impart protection against A. baumannii. Shahed University. [ABSTRACT FROM AUTHOR]