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We found that messenger RNA and adenovirus vector vaccines transfected lymphatic endothelial cell and fibroblastic reticular cell subsets in vivo and led to early local S protein production in the draining LN in a vaccine-specific manner. The vaccines induced rapid transcriptomic reprogramming of the LN stromal cells, which functionally altered scavenging and parenchymal transfer of lymph-borne antigens, formation of chemokine gradients, and migration of eosinophils within LNs. 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