A method of enhancing the humoral immune response to an S region immunogen encoded by the hepatitis B virus genome in an animal that exhibits a low response to said immunogen, which method comprises introducing into said animal an effective amount of a vaccine constituted by a physiologically tolerable diluent that comprises dispersed therein a potentiating amount of a pre-S(2) region polypeptide encoded by said viral genome that is chemically coupled to an S region immunogen which induces a protective response in an animal that exhibits a response to an S region-containing immunogen, wherein said S region immunogen is an amino acid residue sequence of HBsAg from position 110 to position 137, from the amino-terminus thereof, and wherein said coupled pre-S(2) region polypeptide is in addition to any of said 55-residue polypeptide present in said S region immunogen.