Development and Validation of Two Optimized Multiplexed Serologic Assays for the 9-Valent Human Papillomavirus Vaccine Types

Nolan, Katrina M.; Seaton, Brent L.; Antonello, Joseph; Zhang, Yuhua; Cook, Lauren; Delfino, Krystyn; Rubinstein, Leonard J.; Cheon, Kyeongmi; Group, Thomas; Luxembourg, Alain; Dubey, Sheri

doi:10.1128/msphere.00962-21

Cited by 3 publications

(1 citation statement)

References 30 publications

(44 reference statements)

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“…If a neutralizing antibodies that share the same epitope as the mAb is present at proper concentration in the serum sample, the binding of the mAb to the VLP will be inhibited by antibody in the serum. Merck evaluated the immunogenicity of Gardasil® 16–18 and Gardasil 9® 15,19 in human using cLIA and received marketing approval from the FDA and other regulatory agencies. The method has good specificity but can detect lower neutralizing antibodies in samples.…”

Section: Introductionmentioning

confidence: 99%

Validation of Luminex immunological and competitive Luminex immunological assays for clinical immunogenicity assessment of a 14‐valent recombinant human papillomavirus vaccine

Zhang,

Meng,

et al. 2023

Journal of Medical Virology

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A novel virus‐like particle (VLP)‐based multivalent recombinant human papillomavirus (HPV) vaccine was developed and evaluated in human, including 14 HPV‐type specific VLP antigens (HPV6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59). The pseudovirus‐based neutralizing assay (PBNA) method is widely used for immunogenicity assessment of HPV vaccine in clinical trials. However, as many as 14 antigen‐specific antibody levels need be determined, PBNA is, for many reasons, challenging and time‐consuming. In this study, we developed a Luminex immunological assay (LIA) and a competitive Luminex immunological assay (cLIA). These methods increase the throughput, reproducibility and precision, as well as reduce the complexity. All assay parameters showed good characteristics in the validation of both methods, benefiting from highly purified and structurally correct VLPs, high specific antibodies, standard VLP‐microspheres and PE‐mAbs conjugating process, adequate assay development and stable system. Validation data support the use of both methods for immunogenicity assessment in clinical trials. LIA showed higher sensitivity than cLIA, and due to limited epitopes of mAb, cLIA detected lower antibody responses, and therefore, fewer antibodies. This work not only supports clinical trials of 14‐valent HPV vaccines more efficiently and reliably, but also provides a set of validation strategies and usable standards for general vaccine immunogenicity testing.

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Section: Introductionmentioning

confidence: 99%

Validation of Luminex immunological and competitive Luminex immunological assays for clinical immunogenicity assessment of a 14‐valent recombinant human papillomavirus vaccine

Zhang,

Meng,

et al. 2023

Journal of Medical Virology

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Ten-Year Follow-up of 9-Valent Human Papillomavirus Vaccine: Immunogenicity, Effectiveness, and Safety

Restrepo,

Herrera,

Samakoses

et al. 2023

Pediatrics

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BACKGROUND AND OBJECTIVES: The 9-valent human papillomavirus (9vHPV) vaccine Phase III immunogenicity study in 9- to 15-year-old boys and girls was extended to assess immunogenicity and effectiveness through 10 years after the last vaccine dose (NCT00943722). METHODS: Boys (n = 301) and girls (n = 971) who received three 9vHPV vaccine doses in the base study (day 1, months 2 and 6) enrolled in the extension. Serum was collected through month 126 for antibody assessments by competitive Luminex immunoassay and immunoglobulin G-Luminex immunoassay. For effectiveness analysis starting at age 16 years, genital swabs were collected (to assess HPV DNA by polymerase chain reaction) and external genital examinations conducted every 6 months. Primary analyses were conducted in per-protocol populations. RESULTS: Geometric mean antibody titers peaked around month 7, decreased sharply between months 7 and 12, then gradually through month 126. Seropositivity rates remained ≥81% by competitive Luminex immunoassay and ≥95% by immunoglobin G-Luminex immunoassay at month 126 for each 9vHPV vaccine type. After up to 11.0 (median 10.0) years of follow-up postdose 3, there were no cases of HPV6/11/16/18/31/33/45/52/58-related high-grade intraepithelial neoplasia or condyloma in males or females. Incidence rates of HPV6/11/16/18/31/33/45/52/58-related 6-month persistent infection in males and females were low (54.6 and 52.4 per 10000 person-years, respectively) and within ranges expected in vaccinated cohorts, based on previous human papillomavirus vaccine efficacy trials. CONCLUSIONS: The 9vHPV vaccine demonstrated sustained immunogenicity and effectiveness through ∼10 years post 3 doses of 9vHPV vaccination of boys and girls aged 9 to 15 years.

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Immunogenicity and Safety of Extended-Interval 2-Dose Regimens of 9vHPV Vaccine

Klein,

Wiesner,

Bautista

et al. 2024

Pediatrics

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BACKGROUND: Nine-valent human papillomavirus (9vHPV) vaccines can be administered in 2 doses 6 to 12 months apart in adolescents. The impact of extended dose intervals is unknown. We report immunogenicity and safety data in adolescents of a second 9vHPV vaccine dose administered ≥1 year after the first. METHODS: This open-label safety and immunogenicity study (NCT04708041) assessed extended-interval 2-dose regimens of 9vHPV vaccine among adolescents (10 to 15 years) who received 2 9vHPV vaccine doses: the first ≥1 year before enrollment, and second, at enrollment (day 1). We measured serologic responses to vaccine-targeted human papillomavirus (HPV) types at enrollment day 1 (pre-dose 2) and 1 month post-dose 2 (month 1) using a competitive LuminexV® immunoassay. We estimated effects of dose interval on geometric mean titers (GMTs) using regression modeling. Participants reported adverse events (AEs) through 15 days after vaccination. RESULTS: We enrolled 146 adolescents (mean age 13.3 years) with median 25 months since first 9vHPV vaccine dose (range: 12–53 months). Across vaccine-targeted HPV types, GMTs increased from day 1 to month 1; seropositivity at month 1 was 100%. Anti-HPV GMTs at month 1 were not affected by differences in dose interval of 12 to 53 months, based on regression modeling. The most common AEs were mild-to-moderate injection site reactions; no serious AEs were reported. CONCLUSIONS: Extending the interval between first and second 9vHPV vaccine doses to 12 to 53 months did not affect antibody responses, with favorable safety profile. These results support feasibility of extended interval regimens for 9vHPV vaccine.

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Development and Validation of Two Optimized Multiplexed Serologic Assays for the 9-Valent Human Papillomavirus Vaccine Types

Abstract: Assay modernization is a key aspect of vaccine life cycle management. Thus, new, reoptimized versions of two 9vHPV immunoassays have been developed and validated for use in ongoing and future HPV vaccine clinical trials.

Cited by 3 publications

References 30 publications

Validation of Luminex immunological and competitive Luminex immunological assays for clinical immunogenicity assessment of a 14‐valent recombinant human papillomavirus vaccine

Validation of Luminex immunological and competitive Luminex immunological assays for clinical immunogenicity assessment of a 14‐valent recombinant human papillomavirus vaccine

Ten-Year Follow-up of 9-Valent Human Papillomavirus Vaccine: Immunogenicity, Effectiveness, and Safety

Immunogenicity and Safety of Extended-Interval 2-Dose Regimens of 9vHPV Vaccine

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