biostudies-otherUnknownMatthew WiestMus musculus (mouse)https://www.ebi.ac.uk/biostudies/studies/S-BSST3402biostudies-otherVivian YanSeok-Chan ParkChun ChenPamela T WongMoataz NoureddineAdolfo Garcia-SastreJames R Baker JrMichael SchotsaertKatarzyna W JanczakJessica J O’KonekDilara KaradagMatthew WiestJulianne d’AcunzoMohammad FarazuddinChinghan ChungGabriel LaghlalifalseSpatiotemporal heterologous vaccination relies on type I interferons at priming to enhance mucosal immunityParenteral vaccines against respiratory viruses poorly block infection and transmission due to suboptimal induction of mucosal immunity. In contrast, hybrid immunity and heterologous-route immunization regimens generate protective mucosal and systemic immunity. Herein, we examine how chronological order in heterologous prime/boost immunization regimens impacts immune responses using combinations of intramuscular mRNA and intranasal adjuvanted subunit vaccines against SARS-CoV-2. Enhanced long-lived mucosal and systemic immunity depended strongly on vaccine delivery sequence, with heterologous regimens administered in alternate order of routes yielding markedly distinct immune profiles with different Th-biases and divergent localizations. Immunity imparted through heterologous immunization 2026-09-23T00:00:00Z2026-09-23T16:20:06.398Z2026-09-21T18:05:26.641ZS-BSST3402