Maintenance of Antibody Avidity in Alaska Native Adolescents Receiving Quadrivalent Human Papillomavirus (HPV) Vaccine

Abstract

BackgroundHuman papillomavirus (HPV) is the most common sexually transmitted infection worldwide, and some types are causally associated with cervical and other types of cancers in women and men. Currently available prophylactic anti‐HPV vaccines are highly effective, eliciting high antibody titers. In the United States, the most commonly used HPV vaccine through 2015 was quadrivalent vaccine (4vHPV), which protects against HPV types 6, 11, 16, and 18. However, the minimum antibody threshold required for protection has not been established. Antibody avidity, a measure of how strongly antibodies bind their cognate antigen, is associated with clearance of many pathogens, and has been proposed as an additional measure of antibody activity against HPV. Few antibody avidity studies have been conducted on HPV vaccine recipients.ObjectiveWe assessed antibody titers and antibody avidity three years after 4vHPV vaccination among a longitudinal cohort of Alaskan Native girls.MethodsParticipants were Alaskan Native children and adolescents who were vaccinated with 3 doses of 4vHPV (0, 2, and 6 month dosing schedule) between the ages of 9–13 years during 2011–2014 and enrolled in a longitudinal cohort study where antibody response will be followed over a 20 year period. Appropriate consent was obtained. At the time of this study, a total of 34 female participants had provided serum specimens following each dose of 4vHPV and once each year for at least three years following vaccine series completion. We assessed antibody avidity on a total of 202 specimens from these 34 unique participants. Antibody titers to HPV types 6, 11, 16, and 18 were determined using multiplex ELISA. Avidity indices were determined using a modified multiplex ELISA, and calculated as the ratio of IgG antibody bound in the treated versus untreated sample wells.ResultsBoth antibody titer and avidity index increased following each dose of 4vHPV for all four HPV types. There was no significant difference in avidity index following dose 2 versus 3 for either HPV type 6 or HPV type 16. Although antibody titers decreased in the year following 4vHPV series completion, avidity indices remained stable through three years post series completion for all four HPV types. There was no correlation between avidity index and antibody titer for any HPV type. Mean avidity indices and antibody titers after each dose of 4vHPV and annually through three years following series completion for HPV types 6, 11, 16, 18 are shown in the table.ConclusionsAntibody avidity following 4vHPV vaccination of Alaska Native girls with 3‐doses of 4vHPV (at 0, 2, and 6 months) remained persistently high for at least 3 years after vaccination, despite a drop in antibody titer. Although their clinical significance is not clear, the persistence of quality HPV type‐specific antibodies (indicated by avidity) could reflect an effective affinity maturation of B cells that can aid in long‐term protection even as antibody titers drop. Further study of these participants is underway to continue to assess their long‐term antibody response to HPV vaccination.Support or Funding InformationCenters for Disease Control and Prevention Mean avidity index and antibody titer following each dose of 4vHPV and annually through three years post series completion for HPV types 6, Time of blood draw HPV6 HPV11 HPV16 HPV18 Avidity Index Ab titer (AU/mL) Avidity Index Ab titer (AU/mL) Avidity Index Ab titer (IU/mL) Avidity Index Ab titer (IU/mL) Post Dose 1 0.42 6.5 0.36 11.6 0.43 28.7 0.38 8 Post Dose 2 0.63 47.3 0.57 58.1 0.74 237.1 0.57 64.7 Post Dose 3 0.63 343.7 0.67 509.5 0.77 1622.6 0.69 561.3 Post Series Year 1 0.64 55.2 0.67 66.8 0.79 259.3 0.67 77.8 Post Series Year 2 0.64 44.7 0.66 68.7 0.79 246.7 0.68 77.9 Post Series Year 3 0.64 25.4 0.66 36.8 0.78 157.1 0.66 56.7