Whole-blood cytokine secretion assay as a high-throughput alternative for assessing the cell-mediated immunity profile after two doses of an adjuvanted SARS-CoV-2 recombinant protein vaccine candidate

被引：13

作者：

De Rosa, Stephen C. ^{[1
]}

Cohen, Kristen W. ^{[1
]}

Bonaparte, Matthew ^{[2
]}

Fu, Bo ^{[3
]}

Garg, Sanjay ^{[4
]}

Gerard, Catherine ^{[5
]}

Goepfert, Paul A. ^{[6
]}

Huang, Ying ^{[1
]}

Larocque, Daniel ^{[7
]}

McElrath, M. Juliana ^{[1
]}

Morris, Daryl ^{[1
]}

Van der Most, Robbert ^{[8
]}

de Bruyn, Guy ^{[9
]}

Pagnon, Anke ^{[7
]}

机构：

[1] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA

[2] Sanofi Pasteur, Global Clin Immunol, Swiftwater, PA USA

[3] Sanofi Pasteur, Biostat, Swiftwater, PA USA

[4] Sanofi Pasteur, R&D Operat, Swiftwater, PA USA

[5] GlaxoSmithKline Vaccines, R&D, Rixensart, Belgium

[6] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA

[7] Sanofi Pasteur, Res Dept, Marcy Letoile, France

[8] GlaxoSmithKline Vaccines, Translat Sci, Rixensart, Belgium

[9] Sanofi Pasteur, Global Clin Dev, Swiftwater, PA USA

来源：

CLINICAL & TRANSLATIONAL IMMUNOLOGY | 2022年 / 11卷 / 01期

基金：

美国国家卫生研究院;

关键词：

adjuvant; AF03; AS03; cell-mediated immunity; CoV2-PreS-dTM; intracellular cytokine staining; multiplex bead array; SARS-CoV-2 recombinant protein candidate vaccine; whole-blood cytokine secretion assay; INTERFERON-GAMMA; HIV VACCINE; T-CELLS; RESPONSES; COVID-19; DISEASE; IMMUNOGENICITY; OPTIMIZATION; TUBERCULOSIS; SQUALENE;

D O I：

10.1002/cti2.1360

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Objectives. We previously described the Phase I-II evaluation of SARS-CoV-2 recombinant protein candidate vaccine, CoV2-PreSdTM, with AF03- or AS03-adjuvant systems (ClinicalTrials.gov, NCT04537208). Here, we further characterise the cellular immunogenicity profile of this vaccine candidate using a whole-blood secretion assay in parallel to intracellular cytokine staining (ICS) of cryopreserved peripheral blood mononuclear cells (PBMCs). Methods. A randomly allocated subset of 90 healthy, SARS-CoV-2-seronegative adults aged >= 18 years who had received (random allocation) one or two separate injections (on study day [D]1 and D22) of saline placebo or CoV2-PreS-dTM formulated with AS03 or AF03 were included. Cytokine secretion was assessed using a TruCulture (R) whole-blood stimulation system in combination with multiplex bead array, and intracellular cytokine profiles were evaluated on thawed PBMCs following ex vivo stimulation with recombinant S protein at pre-vaccination (D1), post-dose 1 (D22) and post-dose 2 (D36). Results. Both methods detected similar vaccine-induced responses after the first and second doses. We observed a Th1 bias (Th1/Th2 ratio > 1.0) for most treatment groups when analysed in whole blood, mainly characterised by increased IFN-gamma, IL-2 and TNF-alpha secretion. Among participants aged >= 50 years, the Th1/Th2 ratio was higher for those who received vaccine candidate with AS03 versus AF03 adjuvant. ICS revealed that this higher Th1/Th2 ratio resulted from higher levels of IFN-gamma expression and that the vaccine induced polyfunctional CD4(+) T cells. Conclusions. The whole-blood cytokine secretion assay is a high-throughput alternative for assessing the quantity and character of vaccine-induced cellular responses.

引用

页数：15