Immunogenicity of HPV prophylactic vaccines: Serology assays and their use in HPV vaccine evaluation and development

Ligia A Pinto, Joakim Dillner, Simon Beddows, Elizabeth R Unger, Ligia A Pinto, Joakim Dillner, Simon Beddows, Elizabeth R Unger

Abstract

When administered as standard three-dose schedules, the licensed HPV prophylactic vaccines have demonstrated extraordinary immunogenicity and efficacy. We summarize the immunogenicity of these licensed vaccines and the most commonly used serology assays, with a focus on key considerations for one-dose vaccine schedules. Although immune correlates of protection against infection are not entirely clear, both preclinical and clinical evidence point to neutralizing antibodies as the principal mechanism of protection. Thus, immunogenicity assessments in vaccine trials have focused on measurements of antibody responses to the vaccine. Non-inferiority of antibody responses after two doses of HPV vaccines separated by 6 months has been demonstrated and this evidence supported the recent WHO recommendations for two-dose vaccination schedules in both boys and girls 9-14 years of age. There is also some evidence suggesting that one dose of HPV vaccines may provide protection similar to the currently recommended two-dose regimens but robust data on efficacy and immunogenicity of one-dose vaccine schedules are lacking. In addition, immunogenicity has been assessed and reported using different methods, precluding direct comparison of results between different studies and vaccines. New head-to-head vaccine trials evaluating one-dose immunogenicity and efficacy have been initiated and an increase in the number of trials relying on immunobridging is anticipated. Therefore, standardized measurement and reporting of immunogenicity for the up to nine HPV types targeted by the current vaccines is now critical. Building on previous HPV serology assay standardization and harmonization efforts initiated by the WHO HPV LabNet in 2006, new secondary standards, critical reference reagents and testing guidelines will be generated as part of a new partnership to facilitate harmonization of the immunogenicity testing in new HPV vaccine trials.

Keywords: Immunogenicity; Prophylactic HPV L1 VLP vaccines; Serology assays.

Copyright © 2018. Published by Elsevier Ltd.

Figures

Fig. 1
Fig. 1
Three main types of assays have been used in the evaluation of antibody responses to HPV vaccines. (A) Neutralization assays, (B) Competitive immunoassays and (C) ELISA.

References

    1. McCormack P.L., Joura E.A. Spotlight on quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine(Gardasil®) in the prevention of premalignant genital lesions, genital cancer, and genital warts in women. BioDrugs. 2011;25:339–343.
    1. McKeage K., Romanowski B. Spotlight on AS04-adjuvanted human papillomavirus (HPV) types 16 and 18 vaccine (Cervarix®) BioDrugs. 2011;25:265–269.
    1. Lopalco P.L. Spotlight on the 9-valent HPV vaccine. Drug Des Devel Ther. 2017;11:35–44.
    1. Petrosky E., Bocchini J.A., Jr., Hariri S., Chesson H., Curtis C.R., Saraiya M. Use of 9-valent human papillomavirus (HPV) vaccine: updated HPV vaccination recommendations of the advisory committee on immunization practices. MMWR Morb Mortal Wkly Rep. 2015;64:300–304.
    1. FUTURE II Study Group Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. New Engl J Med. 2007;356:1915–1927.
    1. Paavonen J., Jenkins D., Bosch F.X., Naud P., Salmeron J., Wheeler C.M. Efficacy of a prophylactic adjuvanted bivalent L1 virus-like-particle vaccine against infection with human papillomavirus types 16 and 18 in young women: an interim analysis of a phase III double-blind, randomised controlled trial. Lancet. 2007;369:2161–2170.
    1. Garland S.M., Hernandez-Avila M., Wheeler C.M., Perez G., Harper D.M., Leodolter S. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. New Engl J Med. 2007;356:1928–1943.
    1. Joura E.A., Giuliano A.R., Iversen O.E., Bouchard C., Mao C., Mehlsen J. A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. New Engl J Med. 2015;372:711–723.
    1. Drolet M., Benard E., Boily M.C., Ali H., Baandrup L., Bauer H. Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis. Lancet Infect Dis. 2015;15:565–580.
    1. Harro C.D., Pang Y.Y., Roden R.B., Hildesheim A., Wang Z., Reynolds M.J. Safety and immunogenicity trial in adult volunteers of a human papillomavirus 16 L1 virus-like particle vaccine. J Natl Cancer Inst. 2001;93:284–292.
    1. Pinto L.A., Edwards J., Castle P.E., Harro C.D., Lowy D.R., Schiller J.T. Cellular immune responses to human papillomavirus (HPV)-16 L1 in healthy volunteers immunized with recombinant HPV-16 L1 virus-like particles. J Infect Dis. 2003;188:327–338.
    1. Food and Drug Administration. Highlights of prescribing information. Gardasil [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant]; 2006. Available at: [accessed on Aug 16 2017].
    1. Food and Drug Administration. Highlights of prescribing information. Cervarix [human papillomavirus bivalent (types 16, 18) vaccine, recombinant]; 2009. Available at: [accessed on Aug 16 2017].
    1. Food and Drug Administration. Highlights of prescribing information. Gardasil 9 (human papillomavirus 9-valent vaccine, recombinant); 2014. Available at: [accessed on Aug 16 2017].
    1. Caulfield M.J., Shi L., Wang S., Wang B., Tobery T.W., Mach H. Effect of alternative aluminum adjuvants on the absorption and immunogenicity of HPV16 L1 VLPs in mice. Human Vacc. 2007;3:139–145.
    1. Giannini S.L., Hanon E., Moris P., Van Mechelen M., Morel S., Dessy F. Enhanced humoral and memory B cellular immunity using HPV16/18 L1 VLP vaccine formulated with the MPL/aluminium salt combination (AS04) compared to aluminium salt only. Vaccine. 2006;24:5937–5949.
    1. Garcon N., Wettendorff M., Van Mechelen M. Role of AS04 in human papillomavirus vaccine: mode of action and clinical profile. Expert Opin Biol Ther. 2011;11:667–677.
    1. Herrin D.M., Coates E.E., Costner P.J., Kemp T.J., Nason M.C., Saharia K.K. Comparison of adaptive and innate immune responses induced by licensed vaccines for Human Papillomavirus. Hum Vaccin Immunother. 2014;10:3446–3454.
    1. Einstein M.H., Levin M.J., Chatterjee A., Chakhtoura N., Takacs P., Catteau G. Comparative humoral and cellular immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine in healthy women aged 18–45 years: follow-up through Month 48 in a Phase III randomized study. Hum Vaccin Immunother. 2014;10:3455–3456.
    1. Einstein M.H., Takacs P., Chatterjee A., Sperling R.S., Chakhtoura N., Blatter M.M. Comparison of long-term immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine in healthy women aged 18–45 years: end-of-study analysis of a Phase III randomized trial. Hum Vaccin Immunother. 2014;10:3435–3445.
    1. Einstein M.H., Baron M., Levin M.J., Chatterjee A., Fox B., Scholar S. Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 vaccine and HPV-6/11/16/18 vaccine: follow-up from months 12–24 in a Phase III randomized study of healthy women aged 18–45 years. Human Vaccin. 2011;7:1343–1358.
    1. Kreimer A.R., Gonzalez P., Katki H.A., Porras C., Schiffman M., Rodriguez A.C. Efficacy of a bivalent HPV 16/18 vaccine against anal HPV 16/18 infection among young women: a nested analysis within the Costa Rica Vaccine Trial. Lancet Oncol. 2011;12:862–870.
    1. Munoz N., Manalastas R., Jr., Pitisuttithum P., Tresukosol D., Monsonego J., Ault K. Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine in women aged 24–45 years: a randomised, double-blind trial. Lancet. 2009;373:1949–1957.
    1. Nygard M., Saah A., Munk C., Tryggvadottir L., Enerly E., Hortlund M. Evaluation of the long-term anti-human papillomavirus 6 (HPV6), 11, 16, and 18 immune responses generated by the quadrivalent HPV vaccine. Clin Vaccine Immunol. 2015;22:943–948.
    1. Olsson S.E., Kjaer S.K., Sigurdsson K., Iversen O.E., Hernandez-Avila M., Wheeler C.M. Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection. Human Vaccin. 2009;5:696–704.
    1. Romanowski B., Schwarz T.F., Ferguson L., Peters K., Dionne M., Behre U. Sustained immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine administered as a two-dose schedule in adolescent girls: five-year clinical data and modeling predictions from a randomized study. Hum Vaccin Immunother. 2016;12:20–29.
    1. Schwarz T.F., Huang L.M., Medina D.M., Valencia A., Lin T.Y., Behre U. Four-year follow-up of the immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine when administered to adolescent girls aged 10–14 years. J Adolesc Health. 2012;50:187–194.
    1. Villa L.L., Ault K.A., Giuliano A.R., Costa R.L., Petta C.A., Andrade R.P. Immunologic responses following administration of a vaccine targeting human papillomavirus Types 6, 11, 16, and 18. Vaccine. 2006;24:5571–5583.
    1. Beachler D.C., Jenkins G., Safaeian M., Kreimer A.R., Wentzensen N. Natural acquired immunity against subsequent genital human papillomavirus infection: a systematic review and meta-analysis. J Infect Dis. 2016;213:1444–1454.
    1. Naud P.S., Roteli-Martins C.M., De Carvalho N.S., Teixeira J.C., de Borba P.C., Sanchez N. Sustained efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine: final analysis of a long-term follow-up study up to 9.4 years post-vaccination. Hum Vaccin Immunother. 2014;10:2147–2162.
    1. Ferris D., Samakoses R., Block S.L., Lazcano-Ponce E., Restrepo J.A., Reisinger K.S. Long-term study of a quadrivalent human papillomavirus vaccine. Pediatrics. 2014;134:e657–e665.
    1. Roteli-Martins C.M., Naud P., De Borba P., Teixeira J.C., De Carvalho N.S., Zahaf T. Sustained immunogenicity and efficacy of the HPV-16/18 AS04-adjuvanted vaccine: up to 8.4 years of follow-up. Hum Vaccin Immunother. 2012;8:390–397.
    1. Safaeian M., Porras C., Schiffman M., Rodriguez A.C., Wacholder S., Gonzalez P. Epidemiological study of anti-HPV16/18 seropositivity and subsequent risk of HPV16 and -18 infections. J Natl Cancer Inst. 2010;102:1653–1662.
    1. Castellsague X., Naud P., Chow S.N., Wheeler C.M., Germar M.J., Lehtinen M. Risk of newly detected infections and cervical abnormalities in women seropositive for naturally acquired human papillomavirus type 16/18 antibodies: analysis of the control arm of PATRICIA. J Infect Dis. 2014;210:517–534.
    1. Scherer E.M., Smith R.A., Gallego D.F., Carter J.J., Wipf G.C., Hoyos M. A single human papillomavirus vaccine dose improves B cell memory in previously infected subjects. EBioMedicine. 2016;10:55–64.
    1. Wheeler C.M., Kjaer S.K., Sigurdsson K., Iversen O.E., Hernandez-Avila M., Perez G. The impact of quadrivalent human papillomavirus (HPV; types 6, 11, 16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in sexually active women aged 16–26 years. J Infect Dis. 2009;199:936–944.
    1. Paavonen J., Naud P., Salmeron J., Wheeler C.M., Chow S.N., Apter D. Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women. Lancet. 2009;374:301–314.
    1. Bissett S.L., Godi A., Jit M., Beddows S. Seropositivity to non-vaccine incorporated genotypes induced by the bivalent and quadrivalent HPV vaccines: a systematic review and meta-analysis. Vaccine. 2017;35:3922–3929.
    1. Breitburd F., Kirnbauer R., Hubbert N.L., Nonnenmacher B., Trin-Dinh-Desmarquet C., Orth G. Immunization with viruslike particles from cottontail rabbit papillomavirus (CRPV) can protect against experimental CRPV infection. J Virol. 1995;69:3959–3963.
    1. Day P.M., Thompson C.D., Buck C.B., Pang Y.Y., Lowy D.R., Schiller J.T. Neutralization of human papillomavirus with monoclonal antibodies reveals different mechanisms of inhibition. J Virol. 2007;81:8784–8792.
    1. Pinto L.A., Kemp T.J., Torres B.N., Isaacs-Soriano K., Ingles D., Abrahamsen M. Quadrivalent human papillomavirus (HPV) vaccine induces HPV-specific antibodies in the oral cavity: results from the mid-adult male vaccine trial. J Infect Dis. 2016;214:1276–1283.
    1. Kemp T.J., Garcia-Pineres A., Falk R.T., Poncelet S., Dessy F., Giannini S.L. Evaluation of systemic and mucosal anti-HPV16 and anti-HPV18 antibody responses from vaccinated women. Vaccine. 2008;26:3608–3616.
    1. Nardelli-Haefliger D., Wirthner D., Schiller J.T., Lowy D.R., Hildesheim A., Ponci F. Specific antibody levels at the cervix during the menstrual cycle of women vaccinated with human papillomavirus 16 virus-like particles. J Natl Cancer Inst. 2003;95:1128–1137.
    1. Petaja T., Pedersen C., Poder A., Strauss G., Catteau G., Thomas F. Long-term persistence of systemic and mucosal immune response to HPV-16/18 AS04-adjuvanted vaccine in preteen/adolescent girls and young women. Int J Cancer. 2011;129:2147–2157.
    1. Longet S., Schiller J.T., Bobst M., Jichlinski P., Nardelli-Haefliger D. A murine genital-challenge model is a sensitive measure of protective antibodies against human papillomavirus infection. J Virol. 2011;85:13253–13259.
    1. Stanley M.A., Sudenga S.L., Giuliano A.R. Alternative dosage schedules with HPV virus-like particle vaccines. Exp Rev Vacc. 2014;13:1027–1038.
    1. Toh Z.Q., Licciardi P.V., Fong J., Garland S.M., Tabrizi S.N., Russell F.M. Reduced dose human papillomavirus vaccination: an update of the current state-of-the-art. Vaccine. 2015;33:5042–5050.
    1. Draper E., Bissett S.L., Howell-Jones R., Waight P., Soldan K., Jit M. A randomized, observer-blinded immunogenicity trial of Cervarix® and Gardasil® human papillomavirus vaccines in 12–15 year old girls. PLoS One. 2013;8:e61825.
    1. Guevara A., Cabello R., Woelber L., Duarte Moreira Jr E., Joura E.A., Reich O. Antibody persistence and evidence of immune memory at 5 years following administration of the 9-valent HPV vaccine. Vaccine. 2017;35:5050–5057.
    1. Petersen L.K., Restrepo J., Moreira E.D., Jr., Iversen O.E., Pitisuttithum P., Van Damme P. Impact of baseline covariates on the immunogenicity of the 9-valent HPV vaccine – a combined analysis of five phase III clinical trials. Papillomavirus Res. 2017;3:105–115.
    1. Giuliano A.R., Lazcano-Ponce E., Villa L., Nolan T., Marchant C., Radley D. Impact of baseline covariates on the immunogenicity of a quadrivalent (types 6, 11, 16, and 18) human papillomavirus virus-like-particle vaccine. J Infect Dis. 2007;196:1153–1162.
    1. Iversen O.E., Miranda M.J., Ulied A., Soerdal T., Lazarus E., Chokephaibulkit K. Immunogenicity of the 9-valent HPV vaccine using 2-dose regimens in girls and boys vs a 3-dose regimen in women. JAMA. 2016;316:2411–2421.
    1. Dobson M., McNeil S., Dionne M., Dawar M., Olgivie G. Immunogenicity of 2 doses of HPV vaccine in younger adolescents in young women. JAMA. 2013;309:1793–1802.
    1. Romanowski B., Schwarz T., Ferguson L., Ferguson M. Immune response to the HPV-16/18 ASO4-adjuvanted vaccine administered as a 2-dose or 3-dose schedule up to 4 years after vaccination: Results from a randomized study. Hum Vaccin Immunother. 2013;10:1155–1165.
    1. Meites E., Kempe A., Markowitz L.E. Use of a 2-dose schedule for human papillomavirus vaccination – updated recommendations of the advisory committee on immunization practices. MMWR. 2016;65:1405–1408.
    1. Safaeian M., Porras C., Pan Y., Kreimer A., Schiller J.T., Gonzalez P. Durable antibody responses following one dose of the bivalent human papillomavirus L1 virus-like particle vaccine in the Costa Rica Vaccine Trial. Cancer Prev Res (Phila) 2013;6:1242–1250.
    1. Sankaranarayanan R., Prabhu P.R., Pawlita M., Gheit T., Bhatla N., Muwonge R. Immunogenicity and HPV infection after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre prospective cohort study. Lancet Oncol. 2016;17:67–77.
    1. Neuzil K.M., Canh D.G., Thiem V.D., Janmohamed A., Huong V.M., Tang Y. Immunogenicity and reactogenicity of alternative schedules of HPV vaccine in Vietnam: a cluster randomized noninferiority trial. JAMA. 2011;305:1424–1431.
    1. Lamontagne D.S., Thiem V.D., Huong V.M., Tang Y., Neuzil K.M. Immunogenicity of quadrivalent HPV vaccine among girls 11 to 13 years of age vaccinated using alternative dosing schedules: results 29 to 32 months after third dose. J Infect Dis. 2013;208:1325–1334.
    1. Leung T.F., Liu A.P., Lim F.S., Thollot F., Oh H.M., Lee B.W. Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine administered according to 2- and 3-dose schedules in girls aged 9–14 years: Results to month 12 from a randomized trial. Hum Vaccin Immunother. 2015;11:1689–1702.
    1. Stanley M. Immunobiology of HPV and HPV vaccines. Gynecol Oncol. 2008;109:S15–S21.
    1. Schiller J.T., Lowy D.R. Immunogenicity testing in human papillomavirus virus-like-particle vaccine trials. J Infect Dis. 2009;200:166–171.
    1. Pastrana D.V., Buck C.B., Pang Y.Y., Thompson C.D., Castle P.E., FitzGerald P.C. Reactivity of human sera in a sensitive, high-throughput pseudovirus-based papillomavirus neutralization assay for HPV16 and HPV18. Virology. 2004;321:205–216.
    1. Dias D., Van Doren J., Schlottmann S., Kelly S., Puchalski D., Ruiz W. Optimization and validation of a multiplexed luminex assay to quantify antibodies to neutralizing epitopes on human papillomaviruses 6, 11, 16, and 18. Clin Diagn Lab Immunol. 2005;12:959–969.
    1. Opalka D., Lachman C.E., MacMullen S.A., Jansen K.U., Smith J.F., Chirmule N. Simultaneous quantitation of antibodies to neutralizing epitopes on virus-like particles for human papillomavirus types 6, 11, 16, and 18 by a multiplexed luminex assay. Clin Diagn Lab Immunol. 2003;10:108–115.
    1. Opalka D., Matys K., Bojczuk P., Green T., Gesser R., Saah A. Multiplexed serologic assay for nine anogenital human papillomavirus types. Clin Vacc Immunol. 2010;17:818–827.
    1. Dessy F.J., Giannini S.L., Bougelet C.A., Kemp T.J., David M.P., Poncelet S.M. Correlation between direct ELISA, single epitope-based inhibition ELISA and pseudovirion-based neutralization assay for measuring anti-HPV-16 and anti-HPV-18 antibody response after vaccination with the AS04-adjuvanted HPV-16/18 cervical cancer vaccine. Human Vaccin. 2008;4:425–434.
    1. World Health Organization . 1st ed. Switzerland; Geneva: 2010. Human papillomavirus laboratory manual.
    1. Waterboer T., Sehr P., Michael K.M., Franceschi S., Nieland J.D., Joos T.O. Multiplex human papillomavirus serology based on in situ-purified glutathione s-transferase fusion proteins. Clin Chem. 2005;51:1845–1853.
    1. Faust H., Knekt P., Forslund O., Dillner J. Validation of multiplexed human papillomavirus serology using pseudovirions bound to heparin-coated beads. J Gen Virol. 2010;91:1840–1848.
    1. Robbins H.A., Kemp T.J., Porras C., Rodriguez A.C., Schiffman M., Wacholder S. Comparison of antibody responses to human papillomavirus vaccination as measured by three assays. Front Oncol. 2014;3:328.
    1. Robbins H.A., Waterboer T., Porras C., Kemp T.J., Pawlita M., Rodriguez A.C. Immunogenicity assessment of HPV16/18 vaccine using the glutathione S-transferase L1 multiplex serology assay. Hum Vaccin Immunother. 2014;10:2965–2974.
    1. Panicker G., Rajbhandari I., Gurbaxani B.M., Querec T.D., Unger E.R. Development and evaluation of multiplexed immunoassay for detection of antibodies to HPV vaccine types. J Immunol Methods. 2015;417:107–114.
    1. Brown D., Muller M., Sehr P., Pawlita M., Seitz H., Rubio I. Concordance assessment between a multiplexed competitive Luminex immunoassay, a multiplexed IgG Luminex immunoassay, and a pseudovirion-based neutralization assay for detection of human papillomaviruse types 16 and 18. Vaccine. 2014;32:5880–5887.
    1. Schiller J.T., Lowy D.R. Understanding and learning from the success of prophylactic human papillomavirus vaccines. Nat Rev Microbiol. 2012;10:681–692.
    1. Buck C.B., Pastrana D.V., Lowy D.R., Schiller J.T. Generation of HPV pseudovirions using transfection and their use in neutralization assays. Methods Mol Med. 2005;119:445–462.
    1. Nie J., Liu Y., Huang W., Wang Y. Development of a triple-color pseudovirion-based assay to detect neutralizing antibodies against human papillomavirus. Viruses. 2016;8:107.
    1. Sehr P., Rubio I., Seitz H., Putzker K., Ribeiro-Muller L., Pawlita M. High-throughput pseudovirion-based neutralization assay for analysis of natural and vaccine-induced antibodies against human papillomaviruses. PLoS One. 2013;8:e75677.
    1. Godi A., Bissett S.L., Miller E., Beddows S. Relationship between humoral immune responses against HPV16, HPV18, HPV31 and HPV45 in 12–15 year old girls receiving Cervarix® or Gardasil® vaccine. PLoS One. 2015;10:e0140926.
    1. Scherpenisse M., Mollers M., Schepp R.M., Boot H.J., de Melker H.E., Meijer C.J. Seroprevalence of seven high-risk HPV types in the Netherlands. Vaccine. 2012;30:6686–6693.
    1. Ferguson M., Wilkinson D.E., Zhou T. WHO meeting on the standardization of HPV assays and the role of the WHO HPV Laboratory Network in supporting vaccine introduction held on 24–25 January 2008, Geneva, Switzerland. Vaccine. 2009;27:337–347.
    1. Eklund C., Unger E.R., Nardelli-Haefliger D., Zhou T., Dillner J. International collaborative proficiency study of Human Papillomavirus type 16 serology. Vaccine. 2012;30:294–299.
    1. Ferguson M., Heath A., Johnes S., Pagliusi S., Dillner J. Results of the first WHO international collaborative study on the standardization of the detection of antibodies to human papillomaviruses. Int J Cancer. 2006;118:1508–1514.
    1. Bissett S.L., Wilkinson D., Tettmar K.I., Jones N., Stanford E., Panicker G. Human papillomavirus antibody reference reagents for use in postvaccination surveillance serology. Clin Vacc Immunol. 2012;19:449–451.
    1. Safaeian M., Sampson J.N., Pan Y., Porras C., Kemp T., Gonzalez P. Durability of protection afforded by fewer doses of the HPV16/18 vaccine: the CVT trial. J Nat Canc Inst. 2018;110:djx158.
    1. Donken R., Schurink-Van't Klooster T.M., Schepp R.M., van der Klis F.R., Knol M.J., Meijer C.J. Immune responses after 2 versus 3 doses of HPV vaccination up to 4½ years after vaccination: An observational study among Dutch routinely vaccinated girls. J Infect Dis. 2017;215:359–366.
    1. Brady A.M., Unger E.R., Panicker G. Description of a novel multiplex avidity assay for valuating HPV antibodies. J Immunol Methods. 2017;447:31–36.
    1. Dauner J.G., Pan Y., Hildesheim A., Kemp T.J., Porras C., Pinto L.A. Development and application of a GuHCl-modified ELISA to measure the avidity of anti-HPV L1 VLP antibodies in vaccinated individuals. Mol Cell Probes. 2012;26:73–80.
    1. Kemp T.J., Safaeian M., Hildesheim A., Pan Y., Penrose K.J., Porras C. Kinetic and HPV infection effects on cross-type neutralizing antibody and avidity responses induced by Cervarix®. Vaccine. 2012;31:165–170.
    1. Boxus M., Lockman L., Fochesato M., Lorin C., Thomas F., Giannini S.L. Antibody avidity measurements in recipients of Cervarix vaccine following a two-dose schedule or a three-dose schedule. Vaccine. 2014;32:3232–3236.
    1. Bachmann M.F., Kalinke U., Althage A., Freer G., Burkhart C., Roost H. The role of antibody concentration and avidity in antiviral protection. Science. 1997;276:2024–2027.
    1. Olsson S.E., Villa L.L., Costa R.L., Petta C.A., Andrade R.P., Malm C. Induction of immune memory following administration of a prophylactic quadrivalent human papillomavirus (HPV) types 6/11/16/18 L1 virus-like particle (VLP) vaccine. Vaccine. 2007;25:4931–4939.
    1. Toh Z.Q., Russell F.M., Reyburn R., Fong J., Tuivaga E., Ratu T. Sustained antibody responses 6 years following 1, 2, or 3 doses of quadrivalent human papillomavirus (HPV) vaccine in adolescent Fijian gGirls, and subsequent responses to a single dose of bBivalent HPV vaccine: A prospective cohort study. Clin Infect Dis. 2017;64:852–859.
    1. Day P.M., Kines R.C., Thompson C.D., Jagu S., Roden R.B., Lowy D.R. In vivo mechanisms of vaccine-induced protection against HPV infection. Cell Host Microbe. 2010;8:260–270.

Source: PubMed

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