Analyzing cellular immunogenicity in vaccine clinical trials: a new statistical method including non-specific responses for accurate estimation of vaccine effect
dc.rights.license | open | en_US |
hal.structure.identifier | Statistics In System biology and Translational Medicine [SISTM] | |
hal.structure.identifier | Bordeaux population health [BPH] | |
dc.contributor.author | LHOMME, Edouard | |
hal.structure.identifier | Statistics In System biology and Translational Medicine [SISTM] | |
hal.structure.identifier | Bordeaux population health [BPH] | |
dc.contributor.author | HEJBLUM, Boris
ORCID: 0000-0003-0646-452X IDREF: 189970316 | |
dc.contributor.author | LACABARATZ, C. | |
dc.contributor.author | WIEDEMANN, A. | |
dc.contributor.author | LELIEVRE, J. D. | |
dc.contributor.author | LEVY, Y. | |
hal.structure.identifier | Statistics In System biology and Translational Medicine [SISTM] | |
hal.structure.identifier | Bordeaux population health [BPH] | |
dc.contributor.author | THIEBAUT, Rodolphe | |
hal.structure.identifier | Statistics In System biology and Translational Medicine [SISTM] | |
hal.structure.identifier | Bordeaux population health [BPH] | |
dc.contributor.author | RICHERT, Laura | |
dc.date.accessioned | 2021-02-03T14:27:32Z | |
dc.date.available | 2021-02-03T14:27:32Z | |
dc.date.issued | 2020 | |
dc.identifier.issn | 1872-7905 (Electronic) 0022-1759 (Linking) | en_US |
dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/26124 | |
dc.description.abstractEn | Evaluation of immunogenicity is a key step in the clinical development of novel vaccines. T-cell responses to vaccine candidates are typically assessed by intracellular cytokine staining (ICS) using multiparametric flow cytometry. A conventional statistical approach to analyze ICS data is to compare, between vaccine regimens or between baseline and post-vaccination of the same regimen depending on the trial design, the percentages of cells producing a cytokine of interest after ex vivo stimulation of peripheral blood mononuclear cells (PBMC) with vaccine antigens, after subtracting the non-specific response (of unstimulated cells) of each sample. Subtraction of the non-specific response is aimed at capturing the specific response to the antigen, but raises methodological issues related to measurement error and statistical power. We describe here a new statistical approach to analyze ICS data from vaccine trials. We propose a bivariate linear regression model for estimating the non-specific and antigen-specific ICS responses. We benchmarked the performance of the model in terms of both bias and control of type-I and -II errors in comparison with conventional approaches, and applied it to simulated data as well as real pre- and post-vaccination data from two recent HIV vaccine trials (ANRS VRI01 in healthy volunteers and therapeutic VRI02 ANRS 149 LIGHT in HIV-infected participants). The model was as good as the conventional approaches (with or without subtraction of the non-specific response) in all simulation scenarios in terms of statistical performance, whereas the conventional approaches did not provide robust results across all scenarios. The proposed model estimated the T-cell responses to the antigens without any effect of the non-specific response on the specific response, irrespective of the correlation between the non-specific and specific responses. This novel method of analyzing T-cell immunogenicity data based on bivariate modeling is more flexible than conventional methods, and so yields more detailed results and enables accurate interpretation of vaccine-induced response. | |
dc.language.iso | EN | en_US |
dc.subject | SISTM | |
dc.title.en | Analyzing cellular immunogenicity in vaccine clinical trials: a new statistical method including non-specific responses for accurate estimation of vaccine effect | |
dc.title.alternative | J Immunol Methods | en_US |
dc.type | Article de revue | en_US |
dc.identifier.doi | 10.1016/j.jim.2019.112711 | |
dc.subject.hal | Sciences du Vivant [q-bio]/Santé publique et épidémiologie | en_US |
dc.identifier.pubmed | 31809708 | en_US |
bordeaux.journal | Journal of Immunological Methods | en_US |
bordeaux.page | 112711 | en_US |
bordeaux.volume | 477 | en_US |
bordeaux.hal.laboratories | Bordeaux Population Health Research Center (BPH) - U1219 | en_US |
bordeaux.institution | Université de Bordeaux | en_US |
bordeaux.team | SISTM_BPH | |
bordeaux.peerReviewed | oui | en_US |
bordeaux.inpress | non | en_US |
hal.identifier | hal-03161945 | |
hal.version | 1 | |
hal.date.transferred | 2021-03-23T09:41:30Z | |
hal.export | true | |
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