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 4 publications

(1 citation statement)

References 30 publications

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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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The 13-year long-term follow-up on the effectiveness and immunogenicity of the quadrivalent human papillomavirus vaccine in Chinese females vaccinated at 20–45 years of age

Wen,

Xu,

Pan

et al. 2024

Human Vaccines & Immunotherapeutics

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The quadrivalent human papillomavirus (qHPV) vaccine demonstrated high efficacy against vaccine-type-related precancers in Chinese females through a 6.6-year double-blind, randomized control trial (V501–041, NCT00834106). We present results for its long-term follow-up (LTFU) phase, evaluating vaccine effectiveness and immunogenicity throughout 13 years post Dose 1. Participants receiving qHPV vaccines at ages 20–45 in the V501–041 study constituted the early vaccination group (EVG). Those who received the placebo in V501–041 but were vaccinated during 2018–2020 formed the catch-up vaccination group (CVG), while the control group (CG) comprised those remaining unvaccinated throughout V501–041 and LTFU. The primary endpoint was histopathologically-confirmed cervical intraepithelial neoplasia (CIN) 2+ tested PCR-positive for HPV-16/18. Antibodies against HPV-6, 11, 16, and 18 were assessed using an immunoglobulin G (IgG) Luminex immunoassay at year 13. A total of 1100 participants from V501–041, of whom 978 were followed in LTFU, were included with a median follow-up of 152.2 months. No cases of the primary endpoint were observed in the EVG during 5513.6 person-years of follow-up, while one case was observed in the CG over 2951.4 person-years of follow-up, indicating a 100% risk reduction in the EVG compared to the CG. In the CVG, no cases were detected from vaccination to the latest follow-up (0.0 per 10 000 person-years), contrasting with an incidence of 22.3 per 10 000 person-years prior to vaccination. Seropositivity rates at year 13 remained >92% (for HPV-6/11/16) and 84% (HPV-18). These findings demonstrated continued vaccine protection against cervical precancers and sustained immunogenicity through 13 years post-vaccination. Trial Registration The LTFU study was registered at the Chinese Clinical Trial Registry, ChiCTR2100052313.

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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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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 4 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

The 13-year long-term follow-up on the effectiveness and immunogenicity of the quadrivalent human papillomavirus vaccine in Chinese females vaccinated at 20–45 years of age

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

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