INTRACUTANEOUS VACCINATION OF RABBITS WITH THE E6 GENE OF COTTONTAIL RABBIT PAPILLOMAVIRUS PROVIDES PARTIAL PROTECTION AGAINST VIRUS CHALLENGE

DNA vaccination of rabbit skin with the L1 gene of cottontail rabbit p apillomavirus (CRPV) has previously been shown to induce prophylactic immunity against CRPV. We now describe the effects of vaccination with the CRPV E6 gene, using the same approach. The experimental vaccine p dCMV-E6 encoded both the truncated and full length forms of CRPV E6 pr otein, The control vaccine pCMV-beta encoded beta galactosidase, Rabbi ts were vaccinated with DNA-coated gold particles, using a gene gun. E ach rabbit received an initial vaccination with 30 mu g DNA and 3 week s later a booster vaccination, also with 30 mu g DNA, pdCMV-E6-vaccina ted rabbits developed E6-specific cellular immunity as determined by p roliferation assays using peripheral blood mononuclear cells from anim als prior to challenge, but did not develop detectable humoral immunit y to E6 proteins, as evaluated by ELISA using two different E6 antigen preparations, Control rabbits developed humoral immunity to beta gala ctosidase. All rabbits were challenged by infection of nine skirt site s with live CRPV virus and monitored for papilloma formation. None of four control rabbits was protected at arty of the challenge sites. Of six rabbits vaccinated with pdCMV-E6, two were completely protected an d one was virtually completely protected (tiny papillomas at just two of nine challenge sites), These three rabbits also exhibited significa nt E6-specific in vitro proliferative responses. The four E6 DNA-vacci nated rabbits that were not completely protected exhibited evidence of partial protection: some challenge sites did not form papillomas, pap illoma onset was delayed; papilloma burden was less, These results dem onstrate that partial prophylaxis against papillomavirus-induced disea se can be achieved by intracutaneous vaccination with a recombinant pl asmid encoding the papillomavirus E6 protein. (C) 1998 Elsevier Scienc e Ltd. All rights reserved.