Serology of human papillomavirus type 16

Abstract: Human papillomavirus (HPV) type 16 is the major cause of cervical intraepithelial neoplasia and anogenital cancers. The antibody response to papillomaviruses is a key determinant of protective immunity and forms the basis for prophylactic vaccine development as well as for seroepidemiology. The present thesis has evaluated different methods for HPV antibody measurements, determinants of the HPV antibody response and determinants of HPV neutralizing capacity. Different strategies for serum antibody measurements were investigated employing a theoretical statistical approach as well as real-life evaluations. A least square-weighted modification of parallel line evaluation was developed and found to have optimal precision for evaluation of antibody levels from ELISA data. The major conformational epitopes recognized by antibodies in human sera were mapped using hybrid capsids of HPV16 and HPV11. The major serologic reactivity was directed towards the C-terminal part of the major capsid protein, both for HPV16 and HPV11. Maintaining a native capsid structure was found to be essential for serological specificity of HPV. Presence of HPV antibodies was dependent on sexual history and was strongly correlated with detectability of the same type of HPV DNA among cervical cancer patients. Heparin is a key receptor molecule for binding of HPV to its host cell. Use of heparin for capturing conformationally correct virus-like particles was found to improve the type-specificity of HPV serology. Neutralizing capacity of HPV antibodies was correlated mainly with the total level of IgG to HPV. Sufficient avidity of the antibodies might also contribute to neutralizing capacity.