ORIGINAL RESEARCH article
Front. Immunol.
Sec. Molecular Innate Immunity
Carbohydrate fatty acid monosulfate ester adjuvant enhances the immunogenicity of influenza antigens via TLR4/2-dependent mechanisms
Provisionally accepted
Sruthi VIJAYA RETNAKUMAR1
SURAJ chandrabhan SINGH2
Srinivasa Reddy Bonam1
Camille Chauvin1
Mano Joseph Mathew3
Ida Busch Nielsen4
Christine Boyle5
Luuk Hilgers6Max Søgaard4Peter Paul Platenberg6
Jagadeesh BAYRY7*- 1Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Paris, 75006, France, Paris, France
- 2Unité 872, Centre de Recherche des Cordeliers, Indian Institute of Technology Palakkad, Palakkad, India
- 3Universite Paris-Pantheon-Assas, Paris, France
- 4ExpreS2ion Biotechnologies ApS, Hørsholm, Denmark
- 5EpiVax, 188 Valley Street, Suite 424, Providence, RI, USA, Providence, United States
- 6LiteVax B.V, Oss, The Netherlands., Oss, Netherlands
- 7INSERM, Centre de Recherche des Cordeliers, Paris, France, Indian Institute of Technology Palakkad, Palakkad, India
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Adjuvants are critical for optimizing the efficacy of influenza subunit vaccines, yet currently approved formulations fail to elicit durable and broad protection. Here, we dissect the immunostimulatory mechanisms of a synthetic carbohydrate fatty acid monosulphate ester (CMS), a key immunogenic component of a squalane-in-water emulsion adjuvant currently in phase I clinical trials. Using human peripheral blood mononuclear cell (PBMC)-based assays, we show that CMS markedly enhances antigen‑specific T cell responses to influenza hemagglutinin (HA) peptides. While recombinant H7N9 HA alone poorly activated antigen‑presenting cells, co‑formulation with CMS induced robust dendritic cell (DC) activation, cytokine secretion, and a polyfunctional T helper cell response. Bulk RNA sequencing of CMS‑stimulated DC revealed strong induction of toll‑like receptor (TLR)-driven innate inflammatory pathways. Furthermore, functional blockade experiments confirmed that CMS adjuvanticity depends on TLR4 and TLR2 receptors. These results define the molecular basis of CMS‑driven immune activation and highlight this adjuvant as a promising platform for next‑generation influenza vaccines targeting emerging pandemic strains.
Keywords: adjuvants, Carbohydrate fattyacid monosulfate ester, Dendritic Cells, influenza, T cells, Toll-Like Receptors, Vaccines
Received: 13 Jan 2026; Accepted: 16 Feb 2026.
Copyright: © 2026 VIJAYA RETNAKUMAR, SINGH, Bonam, Chauvin, Mathew, Nielsen, Boyle, Hilgers, Søgaard, Platenberg and BAYRY. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jagadeesh BAYRY
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