Deletion of a major neutralizing epitope of human papillomavirus type 16 virus-like particles

1 Department of Medical Microbiology, Malmö University Hospital, Lund University, UMAS, S-205 02 Malmö, Sweden 2 Active Biotech Research AB, Lund, Sweden Correspondence J. Dillner joakim.dillner{at}med.lu.se Human papillomavirus type 16 (HPV-16) is a major cause of human cancer. Effective prophylactic vaccines are based on type-specific neutralizing antibodies. A major neutralizing epitope has been defined by the monoclonal antibody H16.V5. To investigate the importance of this epitope for overall immunogenicity of HPV-16, HPV-16 virus-like particles devoid of the H16.V5 epitope were engineered by site-directed mutagenesis of ten non-conserved, surface-exposed residues. Removal of the H16.V5-defined epitope had only a marginal effect on antigenic reactivity with antibodies in sera from infected subjects, but affected immunogenicity in experimental immunization of mice, with reduced induction of both antibody responses and CTL responses.