Virus-like particles were produced in insect cells containing either the L1 and L2 capsid proteins of bovine papillomavirus type 4 (BPV-4) or only the L1 protein. Both preparations of VLPs proved to be extremely effective prophylactic vaccines. Thirteen of 15 calves immunised with either L1-L2 VLPs or L1-VLPs were refractory to experimental challenge with high doses of BPV-4 and did not develop papillomas, while 9 of 10 control animals developed multiple oral papillomas. VLPs were not efficient as therapeutic vaccine in calves with established papillomas, although VLP-vaccinated animals appeared to undergo tumour regression more rapidly than nonvaccinated control animals. Antibody responses in VLP-vaccinated calves were associated with prevention of disease but not with regression of papillomas. Thus prophylactic VLP vaccination is effective in preventing disease in this model of mucosal papillomavirus infection. VLPs and native virus share at least some conformational epitopes, as shown by the cross-reactivity of their antibodies.
We have previously shown that cattle vaccinated with L2, the minor structural protein of bovine papillomavirus-4 (BPV-4), do not develop alimentary papillomas upon challenge with BPV-4. Analysis of the B and T cell response in L2-vaccinated animals showed that the majority of the response was directed against the N-terminus and C-terminus of L2 with little response against the middle portion. Cattle were vaccinated with the N-terminus or the C-terminus of L2. The animals vaccinated with the N-terminus were completely protected from viral challenge, whereas the animals vaccinated with the C-terminus were not. Further analysis with synthetic overlapping peptides spanning the entire N-terminus mapped a B cell immunodominant epitope at amino acid 101-120. This epitope was recognised by all vaccinated animals.
Papillomaviruses are ubiquitous DNA viruses affecting humans and animals and causing a variety oftumours of mucosal and cutaneous epithelia. Some of these lesions, particularly those affecting mucosal epithelia, can progress to squamous cell carcinomas. Prevention or cure of viral infection would ultimately lead to a decrease in the incidence of papillomavirus-associated cancers. Using recombinant proteins, we have developed prophylactic and therapeutic vaccines against bovine papiUomavirus type 4, a mucosal papillomavirus implicated in cancer of the alimentary canal in cattle; similar possibilities exist for the human mucosal papillomaviruses.
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