LiteVax-adjuvanted influenza vaccine induces transient interferon-driven innate activation and accelerates early IgG3 responses in older adults

D'Onofrio, V.; Verstraete, M.; Porrez, S.; Jacobs, B.; Alhatemi, A.; De Gussem, S.; Verwilst, S.; Willems, A.; Waerlop, G.; De Meester, E.; Decraene, S.; Van Niewerburgh, F.; Leroux-Roels, G.; van Riet, E.; Platenburg, P. P.; Hilgers, L.; Leroux-Roels, I.

doi:10.64898/2026.07.28.741158

bioRxiv · 10.64898/2026.07.28.741158

LiteVax-adjuvanted influenza vaccine induces transient interferon-driven innate activation and accelerates early IgG3 responses in older adults

D'Onofrio, V.·Verstraete, M.·Porrez, S.·Jacobs, B.·Alhatemi, A.·De Gussem, S.·Verwilst, S.·Willems, A.·Waerlop, G.·De Meester, E.·Decraene, S.·Van Niewerburgh, F.·Leroux-Roels, G.·van Riet, E.·Platenburg, P. P.·Hilgers, L.·Leroux-Roels, I.

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Abstract

Vaccine immunogenicity declines with age due to immunosenescence, underscoring the need for improved adjuvants. LiteVax Adjuvant (LVA), a squalane-in-water emulsion containing carbohydrate fatty-acid monosulphate esters, has shown potential to enhance influenza vaccine responses, but its mechanisms in humans remain unclear. We performed a longitudinal systems vaccinology study in 56 younger (18-45 years) and older ([≥]60 years) adults receiving a quadrivalent influenza vaccine with or without LVA. Multi-omics analyses, including bulk and single-cell transcriptomics, flow cytometry, and serology, revealed that LVA induced a rapid, transient interferon-driven innate response, primarily in monocytes, associated with enhanced antigen processing and dendritic cell to T cell interactions. LVA promoted differentiation of influenza-specific CD4+ T cells toward CD45RO+ memory phenotypes, accelerated early IgG3 antibody responses, and increased IgG-producing plasmablast frequencies without affecting overall antibody magnitude. Importantly, LVA reduced age-related differences in early immune responses, improving response quality and supporting vaccine performance in older adults.

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D'Onofrio, V., Verstraete, M., Porrez, S., Jacobs, B., Alhatemi, A., De Gussem, S., Verwilst, S., Willems, A., Waerlop, G., De Meester, E., Decraene, S., Van Niewerburgh, F., Leroux-Roels, G., van Riet, E., Platenburg, P. P., Hilgers, L., Leroux-Roels, I.. 2026-07-31. LiteVax-adjuvanted influenza vaccine induces transient interferon-driven innate activation and accelerates early IgG3 responses in older adults. https://doi.org/10.64898/2026.07.28.741158

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