Abstract
ObjectivesIn order to assess HPV-specific IgG characteristics, we evaluated multiple aspects of the humoral antibody response that will provide insight in the HPV humoral immune response induced by HPV infection and vaccination.MethodsCross-reactivity of HPV-specific antibodies induced by infection or vaccination was assessed with VLP16 or 18 inhibition using a VLP-based multiplex immunoassay (MIA) for HPV16, 18, 31, 33, 45, 52 and 58. HPV16/18 specific IgG1-4 subclasses and avidity were determined with the VLP-MIA in sera after HPV infection and after vaccination. Neutralizing antibodies were determined in a small subset of single-seropositive and multi-seropositive naturally derived antibodies.ResultsNaturally derived antibodies from single-positive sera were highly genotype-specific as homologue VLP-inhibition percentages varied between 78-94%. In multi-positive sera, cross-reactive antibodies were observed both within and between α7 and α9 species. After vaccination, cross-reactive antibodies were mainly species-specific. Avidity of vaccine-derived HPV-specific antibodies was 3 times higher than that of antibodies induced by HPV infection (p<0.0001). IgG1 and IgG3 were found to be the predominant subclasses observed after HPV infection and vaccination. In the small subset tested, the number of single-positive sera with neutralizing capacity was higher than of multi-positive sera.ConclusionNaturally derived HPV-specific antibodies from single-positive samples showed different characteristics in terms of cross-reactivity and neutralizing capacity compared with antibodies from multi-positive sera. Post-vaccination, HPV antibody avidity was approximately 3 times higher than antibody avidity induced by HPV infection. Therefore, antibody avidity might be a potential surrogate of protection.
Highlights
Persistent infection with high-risk human papillomavirus (HPV) is a necessary event of cervical cancer
We evaluate multiple aspects of the humoral antibody response induced by HPV infection and after prophylactic HPV vaccination
A significant reduction in antibody levels of phylogenetically related HPV types was observed after VLP16 inhibition with inhibition percentages varying between 76% and 88% for HPV31, 33, 52 and 58 (Figure 1A)
Summary
Persistent infection with high-risk (hr) human papillomavirus (HPV) is a necessary event of cervical cancer. Almost all cervical cancers are HPV DNA-positive to at least one of the 15 hr-HPV types that can cause genital infections. After an incidental HPV infection, only 50-70% of the infected individuals develop detectable HPV-specific antibodies in serum mainly directed against the L1 capsid protein of the virus [3]. In contrast to the weak immune response induced by naturally HPV infections, the HPV vaccines induce strong immunogenic responses against HPV16 and 18 in serum [4]. The HPV-specific antibody levels after vaccination in serum are 10-100 times higher as compared to naturally derived antibody levels. Vaccine-derived antibody levels are thought to be largely responsible for the protection against subsequent infection and cervical intraepithelial neoplasia (CIN), the precursors of cervical cancer [4,5]
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