Bacillus anthracis is the etiological agent of anthrax. Protective antigen (PA) has been established as the key protective immunogen and is the major component of anthrax vaccine. Prior studies have indicated that C-terminus host cell receptor binding region contains dominant protective epitopes of PA. In the present study, we focused our attention on determining B-cell epitopes from this region, which could be employed as a vaccine. Using B-cell epitope prediction systems, three regions were identified; ID-I: 604–622, ID-II: 626–676 and ID-III: 707–723 aa residues. These epitopes elicited potent B-cell response in BALB/c mice. ID-II in particular was found to be highly immunogenic in terms of IgG antibody titre, with a predominantly IgG1/IgG2a subclass distribution indicating Th2 bias and high affinity/avidity index. Effective cellular immunity was additionally generated which also signified its Th2 bias. Further, ID-II induced high level of lethal toxin neutralizing antibodies and robust protective immunity (66%) against in vivo lethal toxin challenge. Thus, ID-II can be classified as an immunodominant B-cell epitope and may prove significant in the development of an effective immunoprophylactic strategy against anthrax.