Characteristics of HPV-specific antibody responses induced by infection and vaccination: cross-reactivity, neutralizing activity, avidity and IgG subclasses.
OBJECTIVE
In 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.


METHODS
Cross-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.


RESULTS
Naturally 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.


CONCLUSIONS
Naturally 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.
Laboratory for Infectious Diseases and Screening, National Institute of Public Health and the Environment, Bilthoven, The Netherlands ; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Mirte
M
Scherpenisse
Rutger M
RM
Schepp
Madelief
M
Mollers
Chris J L M
CJ
Meijer
Guy A M
GA
Berbers
Fiona R M
FR
van der Klis
D000293:Adolescent; D000328:Adult; D000368:Aged; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000915:Antibody Affinity / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003429:Cross Reactions / Q000276:immunology*; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology; D052161:Human papillomavirus 18 / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D027383:Papillomaviridae / Q000276:immunology*; D030361:Papillomavirus Infections / Q000097:blood / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D053918:Papillomavirus Vaccines / Q000276:immunology; D013045:Species Specificity; D014611:Vaccination; D055815:Young Adult
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D053918:Papillomavirus Vaccines