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Record W3120554381 · doi:10.1093/ofid/ofaa417.003

4. Immunogenicity of the Adjuvanted Recombinant Zoster Vaccine in Immunocompromised Adults

2020· article· en· W3120554381 on OpenAlexaff
Alemnew F. Dagnew, Peter Vink, Mamadou Dramé, David O. Willer, Bruno Salaun, Anne Schuind

Bibliographic record

VenueOpen Forum Infectious Diseases · 2020
Typearticle
Languageen
FieldMedicine
TopicHerpesvirus Infections and Treatments
Canadian institutionsGlaxoSmithKline (Canada)
Fundersnot available
KeywordsMedicineImmunogenicityVaccinationClinical trialImmunosuppressionImmunologyInternal medicineHematopoietic stem cell transplantationOncologyVirologyAntibodyTransplantation

Abstract

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Abstract Background Immunocompromised (IC) populations are at increased risk of developing herpes zoster (HZ) due to disease- and/or therapy-induced immunosuppression. The adjuvanted recombinant zoster vaccine (RZV) has demonstrated 68.2% efficacy in preventing HZ in autologous hematopoietic stem cell transplant (HSCT) recipients and 87.2% efficacy in a post-hoc analysis in hematologic malignancy (HM) patients ≥ 18 years of age (YOA). Here we present the immunogenicity of RZV in representative IC populations. Methods Our analysis includes five phase I/II/III clinical trials conducted worldwide between 2010–2017 (Table 1) in IC populations (autologous HSCT, human immunodeficiency virus [HIV]-infected, HM, solid tumor [ST] on chemotherapy and renal transplant [RT] patients) ≥ 18 YOA. Anti-glycoprotein E (gE) antibody geometric mean concentrations (GMCs) and gE-specific CD4 T cell frequencies were descriptively evaluated by age group (18–49 YOA and ≥ 50 YOA) and overall at 1 month (M) and 12M post-last RZV dose. Table 1. Clinical studies with immunocompromised populations included in our analysis Results The according-to-protocol cohorts for immunogenicity from the included trials are presented in Table 1. At 1M post-last RZV dose, anti-gE GMCs and median CD4 T-cell frequencies increased in all IC populations compared to pre-vaccination and persisted above baseline up to 12M post-last RZV dose (Figures 1 and 2). No meaningful differences were seen between age groups in terms of humoral (except a slight trend for stronger responses in the 18–49 YOA RT and HM patients compared to their corresponding ≥ 50 YOA group) and gE-specific CD4 T-cell responses in any of the IC populations. Figure 1. Humoral immune responses to RZV in immunocompromised populations (adapted ATP cohort for humoral immunogenicity) Figure 2. Cell-mediated immune responses to RZV in immunocompromised populations (adapted ATP cohort for cell-mediated immunogenicity) Conclusion RZV induced robust and persistent humoral and cell-mediated immune (CMI) responses that lasted up to at least 12M post-last vaccination in all evaluated IC populations. Humoral responses in the IC populations were robust although not as strong as in the non-IC adults ≥ 50 YOA. CMI responses were mostly similar across IC populations and adults ≥ 50 YOA, with a potent response occurring even in ST patients undergoing chemotherapy. This data shows that RZV is immunogenic even in severely IC adults. Funding: GlaxoSmithKline Biologicals SA Acknowledgment: M Maior/S Hulsmans (Modis c/o GSK) provided writing/editorial support Disclosures Alemnew F. Dagnew, MD, MSc, GSK group of companies (Employee, Shareholder) Peter Vink, MD, GSK group of companies (Employee, Shareholder) Mamadou Drame, MSc, GSK group of companies (Employee) David Willer, PhD, GSK group of companies (Employee, Shareholder) Bruno Salaun, PhD, GSK group of companies (Employee) Anne Schuind, MD, GSK (Employee, Other Financial or Material Support, own GSK stock options or restricted shares as part of renumeration)

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.028
Threshold uncertainty score0.568

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.012
GPT teacher head0.265
Teacher spread0.253 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations0
Published2020
Admission routes1
Has abstractyes

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