GSE193419
An adjuvant strategy enabled by modulation of the physical properties of fungal ligands expands viral glycoprotein immunogenicity
Activation of the innate immune system via pattern recognition receptors (PRRs) is key to generate lasting adaptive immunity. PRRs detect unique chemical patterns associated with invading microorganism, but if and how the physical properties of PRR ligands influence development of the immune response remains unknown. Through the study of fungal mannans we show that the physical form of PRR ligands dictates the immune response. Soluble mannans are immunosilent in the periphery but elicit a potent pro-inflammatory response in the draining lymph node (dLN). By modulating the physical form of mannans, we developed a formulation that targets both the periphery and dLN. When combined with viral glycoprotein antigens, this mannan formulation broadens epitope recognition, elicits potent antigen-specific neutralizing antibodies, and confers protection against viral infections of the lung. Thus, the physical properties of microbial ligands determine the outcome of the immune response and can be harnessed for vaccine development. Overall design: Examination of skin and lymph node immune responses to mannans or beta-glucans by RNA-seq