An ultra-sensitive Abbott ARCHITECT ®  assay for the detection of hepatitis B virus surface antigen (HBsAg)

Lou, Sheng C.; Taylor, Russell; Pearce, Sandra; Kuhns, Mary C.; Leary, Thomas P.

doi:10.1016/j.jcv.2018.05.009

Cited by 40 publications

(48 citation statements)

References 25 publications

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“…All testing was performed as recommended in the respective assay package inserts. In addition, samples were tested with a new prototype ARCHITECT qualitative HBsAg assay with improved analytical sensitivity of 0.0052 IU/ml, improved mutant and genotype detection, and specificity of 99.97–100% [11]. The assay is fully automated and requires no sample pretreatment.…”

Section: Methodsmentioning

confidence: 99%

Molecular and serological characterization of hepatitis B vaccine breakthrough infections in serial samples from two plasma donors

Kuhns

McNamara

Holzmayer

et al. 2019

Virol J

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Background Although vaccines for hepatitis B virus (HBV) are highly effective, HBV infections in vaccinees occur. Index samples of breakthrough infections are typically anti-HBc negative but HBV DNA positive with protective anti-HBs levels while HBsAg detection may be delayed or absent. HBsAg mutations have been associated with some vaccine breakthrough cases. Methods This research characterizes the serological and molecular profiles of vaccine breakthrough infections in serial samples from two commercially available plasma donor panels. Samples were tested with commercially available assays for HBV antigens and antibodies: HBsAg, HBeAg, anti-HBc, anti-HBc IgM, anti-HBe, and anti-HBs. Different immunoassay approaches for earlier detection of breakthrough infection were explored including hepatitis B core-related antigen (HBcrAg), a research assay for preS2 antigen, and a new prototype ARCHITECT HBsAg assay with improved sensitivity. The prototype HBsAg assay is fully automated and involves no sample pre-treatment. Molecular testing included HBV DNA quantitation and sequencing of preS1, preS2, surface, and basal core promoter/core promoter genes. Results Although the research preS2 antigen assay allowed earlier detection of the breakthrough infections than current HBsAg assays and HBcrAg, the new prototype ARCHITECT HBsAg assay provided the earliest serologic detection. The ability of the new prototype HBsAg assay to detect HBsAg in the presence of anti-HBs was investigated using known concentrations of native HBsAg mixed with anti-HBs from a vaccinee. The results demonstrated that the prototype ARCHITECT assay is more sensitive in detecting HBsAg in the presence of anti-HBs than current HBsAg assays. Sequencing revealed multiple substitutions in preS1, preS2, and S regions for one panel including a rare D144N substitution associated with vaccine breakthrough that emerged with increasing frequency as the breakthrough infection developed. Conclusions When compared with other immunoassay approaches, the new prototype ARCHITECT HBsAg assay allows earlier detection of vaccine breakthrough infections and more sensitive detection of HBsAg in the presence of anti-HBs. Molecular characterization of longitudinal samples demonstrated the progressive appearance of a rare HBsAg mutation associated with vaccine breakthrough.

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Section: Methodsmentioning

confidence: 99%

Molecular and serological characterization of hepatitis B vaccine breakthrough infections in serial samples from two plasma donors

Kuhns

McNamara

Holzmayer

et al. 2019

Virol J

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“…New assays have increased sensitivity (LLOD and LLOQ of ~0.005 IU/mL), but the clinical relevance of low levels of HBsAg (0.005-0.05 IU/mL) is unclear. (22)(23)(24) There are 2 sources of circulating HBsAg, cccDNA and integrated HBV DNA, with the latter suggested to be a more important source of HBsAg in HBeAg-negative patients. (25) The efficacy of new antiviral or immunomodulatory therapies that inhibit or clear cccDNA may not be well-reflected in HBsAg measurement if integrated HBV DNA continues to produce HBsAg-unless antiviral immune responses are restored and hepatocytes capable of producing HBsAg from cccDNA as well as integrated HBV DNA are eliminated.…”

Section: Reliability Of Current Hbsag Assays To Assess Hbv Functionalmentioning

confidence: 99%

“…Current clinical assays for HBsAg have a lower limit of quantification (LLOQ) and lower LLOD of around 0.05 IU/mL and can detect common HBV S variants. New assays have increased sensitivity (LLOD and LLOQ of ~0.005 IU/mL), but the clinical relevance of low levels of HBsAg (0.005‐0.05 IU/mL) is unclear . There are 2 sources of circulating HBsAg, cccDNA and integrated HBV DNA, with the latter suggested to be a more important source of HBsAg in HBeAg‐negative patients .…”

Section: Endpoint Definitions For Hbv Therapy and Surrogates For Hbv mentioning

confidence: 99%

Guidance for Design and Endpoints of Clinical Trials in Chronic Hepatitis B—Report From the 2019 EASL‐AASLD HBV Treatment Endpoints Conference

et al. 2020

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Representatives from academia, industry, regulatory agencies, and patient groups convened in March 2019 with the primary goal of developing agreement on chronic hepatitis B virus (HBV) treatment endpoints to guide clinical trials aiming to “cure” HBV. Agreement among the conference participants was reached on some key points. “Functional” but not sterilising cure is achievable and should be defined as sustained HBsAg loss in addition to undetectable HBV DNA 6 months post‐treatment. The primary endpoint of phase III trials should be functional cure; HBsAg loss in ≥30% of patients was suggested as an acceptable rate of response in these trials. Sustained virologic suppression (undetectable serum HBV DNA) without HBsAg loss 6 months after discontinuation of treatment would be an intermediate goal. Demonstrated validity for the prediction of sustained HBsAg loss was considered the most appropriate criterion for the approval of new HBV assays to determine efficacy endpoints. Clinical trials aimed at HBV functional cure should initially focus on patients with HBeAg‐positive or negative chronic hepatitis, who are treatment‐naïve or virally suppressed on nucleos(t)ide analogues. A hepatitis flare associated with an increase in bilirubin or international normalised ratio should prompt temporary or permanent cessation of an investigational treatment. New treatments must be as safe as existing nucleos(t)ide analogues. The primary endpoint for phase III trials for HDV coinfection should be undetectable serum HDV RNA 6 months after stopping treatment. On treatment HDV RNA suppression associated with normalisation of alanine aminotransferase is considered an intermediate goal. In conclusion, regarding HBV “functional cure”, the primary goal is sustained HBsAg loss with undetectable HBV DNA after completion of treatment and the intermediate goal is sustained undetectable HBV DNA without HBsAg loss after stopping treatment.

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“…The results of this study are, therefore, still valid for the current situation. It should be mentioned that currently more sensitive HBsAg tests are available with analytical sensitivity of 5·0 mIU/ml , which can significantly reduce the gap to HBV‐NAT to 73 IU/ml HBV DNA at the positive HBsAg cut‐off (range 18–296 IU/ml) [data not shown].…”

Section: Discussionmentioning

confidence: 99%

Detection of hepatitis B virus infection in German blood donors 2008–2015

et al. 2020

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Background and objectives Assessment of HBV-NAT testing compared to HBsAg and anti-HBc screening in German blood establishments for the period 2008-2015.Materials and methods Blood donations screened for HBsAg and anti-HBc along with HBV-NAT were evaluated. Sensitivity of HBsAg and HBV-NAT tests was compared in 30 HBV seroconversion panels and with the viral load of the NATonly cases. Residual risk for HBV in the WP was modelled.Results A total of 45 270 111 donations were evaluated. There were 29 NATonly cases in the HBsAg-negative HBV-WP, one by ID-NAT and 28 by MP-NAT. MP-NAT, on average, showed higher sensitivity than HBsAg testing: MP-NAT-LoD of 146 IU/ml vs. 362 IU/ml HBV DNA for positive HBsAg detection (range 135-1502 IU/ml), resulting in 3Á1 days (range 2Á0-4Á8 days) earlier HBV detection. Viral loads of the NAT-only cases confirmed the sensitivity of the HBV tests in the seroconversion study. One HBsAg-negative case was due to a new HBsAg mutant combination. There was one HBsAg-reactive only case. In addition, HBV incidence in the HBV-WP included 41 HBsAg-/HBV-NAT-positives and three HBV transmission cases. The residual risk for HBsAg was estimated to be 1:1 619 419-1 268 474 compared to 1:2 793 365-2 134 702 for MP-NAT. Within chronic HBV (HBsAg-/anti-HBc-positive and MP-NAT-negative) 70% were ID-NAT positive at low viral load (median 20 IU/ml). Among anti-HBc-only, supplementary ID-NAT detected 23 occult HBV infections. ConclusionsIn the HBV-WP, MP-NAT provided a higher sensitivity than HBsAg testing, obtained a considerably higher yield and reduced the risk for HBV transmission. In later HBV stages, anti-HBc screening and HBV-ID-NAT intercepted potentially infectious donations.

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An ultra-sensitive Abbott ARCHITECT ® assay for the detection of hepatitis B virus surface antigen (HBsAg)

Cited by 40 publications

References 25 publications

Molecular and serological characterization of hepatitis B vaccine breakthrough infections in serial samples from two plasma donors

Molecular and serological characterization of hepatitis B vaccine breakthrough infections in serial samples from two plasma donors

Guidance for Design and Endpoints of Clinical Trials in Chronic Hepatitis B—Report From the 2019 EASL‐AASLD HBV Treatment Endpoints Conference

Detection of hepatitis B virus infection in German blood donors 2008–2015

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