Lipid-based bio-nanohybrids were evaluated as carriers of viral particles in the development of thermally stable and efficacious vaccines against influenza A. Herein, the surfaces of the microfibrous clay sepiolite and the Mg/Al-type layered double hydroxide were modified with a bilayer lipid membrane on which influenza A virions were immobilised. These vaccines were highly immunogenic in mice and stability studies revealed that thermal and lyophilisation resistance were significantly enhanced when compared with a standard aluminium adjuvant. These findings might be attributable to the colloidal behaviour in combination with the biomimetic interface which improves the carrier-virus interactions and preserves the molecular architecture of the viral particles. All these characteristics make the here presented clay–lipid biohybrid materials promising candidates for vaccine formulations.