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Journal Article Epublish 20 citations

PubMed: 35035955 DOI: 10.1002/cti2.1360

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.

Clin Transl Immunology 11(1):e1360

Authors: Stephen C De Rosa, Kristen W Cohen, Matthew Bonaparte, Bo Fu, Sanjay Garg, Catherine Gerard, Paul A Goepfert, Ying Huang, Daniel Larocque, M Juliana McElrath, Daryl Morris, Robbert Van der Most, Guy de Bruyn, Anke Pagnon

Affiliations

  • Vaccine and Infectious Disease Division Fred Hutchinson Cancer Research Center Seattle WA USA.
  • Global Clinical Immunology Sanofi Pasteur Swiftwater PA USA.
  • Biostatics Sanofi Pasteur Swiftwater PA USA.
  • R&D Operations Sanofi Pasteur Swiftwater PA USA.
  • R&D GlaxoSmithKline Vaccines Rixensart Belgium.
  • Department of Medicine University of Alabama at Birmingham Birmingham AL USA.
  • Research Department Sanofi Pasteur Marcy l'Étoile France.
  • Translational Science GlaxoSmithKline Vaccines Rixensart Belgium.
  • Global Clinical Development Sanofi Pasteur Swiftwater PA USA.

Abstract

OBJECTIVES

We previously described the Phase I-II evaluation of SARS-CoV-2 recombinant protein candidate vaccine, CoV2-PreS-dTM, 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 whole-blood stimulation system in combination with multiplex bead array, and intracellular cytokine profiles were evaluated on thawed PBMCs following 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-γ, IL-2 and TNF-α 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-γ 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.

MeSH

Cytokines, Cells, Sars-Cov-2, Blood, Vaccines, Immunity, Cellular, Aged, Immunity, Severe Acute Respiratory Syndrome-Related Coronavirus, Recombinant Proteins

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