Muscle macrophage regenerative response after squalene-adjuvanted influenza vaccination is associated with type II-skewed response and is reduced with age.

Authors

Moataz Noureddine, Lauren A Chang, Farah El Ayache, Gabriel Laghlali, Eleanor Burgess, Leonie Gruneberg, Prajakta Warang, Kaijun Jiang, Johanna Vandekerckhove, Vivian Yan, Haye Nijhuis, Lynda Coughlan, Bruno G De Geest, Juan Garcia-Bernalt Diego, Seok-Chan Park, Jorge Levican, Michael Schotsaert

Published in

NPJ vaccines. Jul 04, 2026. Epub Jul 04, 2026.

Abstract

Squalene-based adjuvants like MF59 and AddaVax induce transient muscle injury, but their downstream mechanisms remain unclear. We show that intramuscular injection of a quadrivalent inactivated influenza vaccine (QIV) with AddaVax triggers a muscle regenerative-like immune response, increasing CX3CR1⁺Ly6C⁺ macrophages in muscle and draining lymph nodes within four days. This promotes a type II-skewed immune response, with elevated IgG1 titers and Th2 cytokines in the lungs after influenza challenge. In aged mice, the macrophage response and type II skewing are diminished. Adoptive transfer of young mice bone marrow-derived macrophages into aged mice at vaccination leads to macrophage antigen uptake, lymph node migration, and type II immune bias. However, this restoration does not improve protection against mismatched viral challenge, suggesting additional age-related immune impairments. These findings highlight the role of macrophage-driven muscle regeneration in adjuvant activity and underscore the need to better understand how muscle damage and repair influence intramuscular vaccine efficacy.

PMID:
42401593
Bibliographic data and abstract were imported from PubMed on 05 Jul 2026.

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