Antibodies to Synthetic Peptides from the PreS1 Region of the Hepatitis B Virus (HBV) Envelope (env) Protein Are Virus-neutralizing and Protective

Hepatitis B virus (HBV) envelope (env) proteins contain three antigenic domains designated S, preS2 and preS1. Studies with synthetic peptide immunogens demonstrated the role of preS2 epitopes in protection against HBV infection. The preS1 domain is implicated in virus-cell receptor interactions suggesting that anti-preS1-specific antibodies should neutralize the infectivity of HBV by blocking virus attachment to cells. We present here evidence that an antiserum to a peptide from the preS1 sequence, anti-preS(21-47), is virus-neutralizing and that active immunization of chimpanzees with a longer peptide derived from the preS1 sequence, preS(12-47), elicits antibodies protective against HBV infection. These results establish the role of the preS1 domain in the process of virus neutralization and the potential of synthetic preS1 analogues for hepatitis B vaccination.