title: Neutralizing and cross-neutralizing antibody titres induced by bivalent and quadrivalent human papillomavirus vaccines in the target population of organized vaccination programmes.
abstract: Aim of this investigator-initiated study was to evaluate and compare the titres of neutralizing and cross-neutralizing antibodies (NAbs) induced by the bivalent (Cervarix(®)) and quadrivalent (Gardasil(®)) HPV vaccines in a cohort of girls aged 11-13 years from organized vaccination programmes. To this aim, HPV16 and HPV18 NAbs were measured by pseudovirion-based neutralization assays in serum collected at 1-6 months after the third vaccine dose in 107 girls vaccinated with Cervarix(®) and 126 vaccinated with Gardasil(®), while HPV31 and HPV45 cross-NAbs were tested in the first 50 consecutive girls of both vaccine groups. The results of this study demonstrated that all vaccinated girls developed HPV16 and HPV18 NAbs, with the exception of two Gardasil(®) vaccinees with undetectable HPV18 NAbs. Geometric mean titres (GMTs) of both HPV16 and HPV18 NAbs were significantly higher in Cervarix(®) than in Gardasil(®) vaccinees [HPV16 NAb GMT 22,136 (95% CI, 18,811-26,073) vs 5092 (4230-6151), respectively; P<0.0001; HPV18 NAb GMT 11,962 (9536-14,363) vs 1804 (1574-2110), respectively; P<0.0001]. Cross-NAbs to HPV31 and HPV45 were detected more frequently Cervarix(®) (HPV31 NAb positivity rates 92.7% and 36%, respectively; P<0.05) than in Gardasil(®) vaccinees (HPV45 NAb positivity rates 56% and 6%, respectively; P<0.0001). The titres of cross-NAbs against HPV31 and HPV45 were also significantly higher in Cervarix(®) than in Gardasil(®) vaccinees [HPV31 NAb GMT 157.2 (95% CI, 92-269) vs 13.0 (6.5-25.8), respectively; P<0.0001; HPV45 NAb GMT 4.7 (2.1-10.2) vs 1.3 (0.3-3.1), respectively; P<0.01]. In conclusion, in adolescent girls vaccinated within organized vaccination programmes, HPV vaccines drive the generation not only of NAbs to HPV vaccine types, but also of cross-NAbs. The bivalent vaccine induced significantly higher HPV16 and HPV18 NAb titres and more frequently and at higher titre HPV31 and HPV45 cross-NAbs than the quadrivalent vaccine.
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova, Italy; Clinical Microbiology and Virology Unit, Padova University Hospital, Padova, Italy. Electronic address: luisa.barzon@unipd.it.
authors.forename: Luisa
authors.initials: L
authors.lastname: Barzon
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Squarzon
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Masiero
authors.affiliation: Clinical Microbiology and Virology Unit, Padova University Hospital, Padova, Italy.
authors.forename: Monia
authors.initials: M
authors.lastname: Pacenti
authors.affiliation: Clinical Microbiology and Virology Unit, Padova University Hospital, Padova, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Marcati
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Mantelli
authors.affiliation: Operative Unit of Clinical Microbiology, St Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Liliana
authors.initials: L
authors.lastname: Gabrielli
authors.affiliation: Servizio Sanità Pubblica, Direzione Generale Sanità e Politiche Sociali, Regione Emilia-Romagna, Bologna, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Pascucci
authors.affiliation: Operative Unit of Clinical Microbiology, St Orsola-Malpighi University Hospital, Bologna, Italy; Department of Specialized, Experimental, and Diagnostic Medicine, University of Bologna, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Lazzarotto
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova, Italy; Clinical Microbiology and Virology Unit, Padova University Hospital, Padova, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Caputo
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova, Italy; Clinical Microbiology and Virology Unit, Padova University Hospital, Padova, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Palù
mesh_terms: D000293:Adolescent; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D002648:Child; D056738:Cross Protection; D005260:Female; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D052162:Human papillomavirus 16; D052161:Human papillomavirus 18; D006801:Humans; D017589:Immunization Programs; D009500:Neutralization Tests; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000627:therapeutic use*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D053918:Papillomavirus Vaccines; C510352:human papillomavirus vaccine, L1 type 16, 18
keywords: Bivalent HPV vaccine; Cervical cancer prevention; Cross-neutralizing antibody; HPV16; HPV18; HPV31; HPV45; Neutralizing antibody; Pseudovirion-based neutralization assay; Quadrivalent HPV vaccine