Evidence map›Paper›PMID 30943997›Full record

ArticleVirology journal2019

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

Mary C Kuhns, Anne L McNamara, Vera Holzmayer, Gavin A Cloherty

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PubMed Full text at PMC Publisher
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Article in Virology journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Mary C KuhnsInfectious Disease Research, Diagnostics Division, Abbott Laboratories, Dept. 09NC, Bldg. AP20, 100 Abbott Park Road, Abbott Park, IL, 60064, USA. Mary.Kuhns@abbott.com.ORCID 0000-0003-0313-9350
Anne L McNamaraInfectious Disease Research, Diagnostics Division, Abbott Laboratories, Dept. 09NC, Bldg. AP20, 100 Abbott Park Road, Abbott Park, IL, 60064, USA.
Vera HolzmayerInfectious Disease Research, Diagnostics Division, Abbott Laboratories, Dept. 09NC, Bldg. AP20, 100 Abbott Park Road, Abbott Park, IL, 60064, USA.
Gavin A ClohertyInfectious Disease Research, Diagnostics Division, Abbott Laboratories, Dept. 09NC, Bldg. AP20, 100 Abbott Park Road, Abbott Park, IL, 60064, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAlthough 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.

methodsThis 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.

resultsAlthough 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.

conclusionsWhen 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.

Indexed as

Blood DonorsSerologic TestsAutomation, LaboratoryDNA, ViralHepatitis BHepatitis B AntibodiesHepatitis B Core AntigensHepatitis B e AntigensHepatitis B Surface AntigensHepatitis B VaccinesHepatitis B virusHumansImmunoassayMutationSensitivity and SpecificityDNA, ViralHepatitis B AntibodiesHepatitis B Core AntigensHepatitis B e AntigensHepatitis B Surface AntigensHepatitis B VaccinesHepatitis B surface antigenHepatitis B surface antigen mutationsHepatitis B virusVaccine breakthrough

Identifiers

PMID30943997
PMCPMC6448254

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.