A PEPTIDE ENCODING A B-CELL EPITOPE FROM THE N-TERMINUS OF THE CAPSIDPROTEIN L2 OF BOVINE PAPILLOMAVIRUS-4 PREVENTS DISEASE

The first 200 N-terminus amino acids of the L2 capsid protein of BPV-L F (designated L2a) are an effective prophylactic vaccine against BPV-4 infection. Vaccination with L2a induces the production of virus neutr alizing antibodies, and when L2a antibodies are removed from immune se ra, the sera lose their neutralization activity. L2a encodes three dom inant a-cell epitopes, defined as epitope 1 (amino acids 101-120), epi tope 2 (aa 131-151), and epitope 3 (aa 151-170). To investigate whethe r any of these epitopes are responsible individually or in combination for protection against viral challenge, synthetic peptides, correspon ding to the three epitopes (peptides 11, 14, and 16, respectively) and conjugated to keyhole limpet hemocyanin (KLH) were tested in vaccinat ion challenge experiments. Calves vaccinated with the three peptides t ogether showed no evidence of papillomavirus infection; those vaccinat ed with peptide 14 alone developed only early lesions which did not pr ogress to proper papillomas and regressed rapidly; those vaccinated wi th peptide 11 or peptide 16 alone were not protected and proceeded to develop papillomas. Therefore the three a-cell epitopes are not conven tionally ''neutralizing'' when presented individually, but in combinat ion they form a complex neutralization domain, and, in particular, epi tope 2, represented by peptide 14, encodes a domain responsible for di sease prevention. (C) 1997 Academic Press.