The F1 antigen of Yersinia pestis has been identified as one of the protective antigens. The present study aims to generate anti-F1 antibodies in mice of different genetic background and to compare antibody profile, isotype distribution and avidity measurement in sera to observe the pattern of immune response as a strategy to develop F1-based immunogen for plague. The study indicated that, although all the immunological parameters were identical, the avidity of the antibodies was considerably different with various strains of mice. Thus, this study may have an implication while developing F1-based vaccine for plague and avidity measurement definitely has a role for antibody function.