Innate immune cell activation by adjuvant AS01 in human lymph node explants is age independent.

Autor: Stylianou VV; Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.; Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia., Bertram KM; Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.; Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia., Vo VA; Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.; Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia., Dunn EB; Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.; Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia., Baharlou H; Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.; Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia., Terre DJ; Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.; Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia., Elhindi J; Research and Education Network, Western Sydney Local Health District, Westmead, New South Wales, Australia., Elder E; Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.; The Westmead Breast Cancer Institute, Westmead, New South Wales, Australia., French J; Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.; The Westmead Breast Cancer Institute, Westmead, New South Wales, Australia., Meybodi F; Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.; The Westmead Breast Cancer Institute, Westmead, New South Wales, Australia., Temmerman ST; GSK, Rixensart, Belgium., Didierlaurent AM; Center of Vaccinology, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland., Coccia M; GSK, Rixensart, Belgium., Sandgren KJ; Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.; Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia., Cunningham AL; Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.; Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Jazyk: angličtina
Zdroj: The Journal of clinical investigation [J Clin Invest] 2024 Sep 24; Vol. 134 (22). Date of Electronic Publication: 2024 Sep 24.
DOI: 10.1172/JCI174144
Abstrakt: Vaccine adjuvants are thought to work by stimulating innate immunity in the draining lymph node (LN), although this has not been proven in humans. To bridge the data obtained in animals to humans, we have developed an in situ human LN explant model to investigate how adjuvants initiate immunity. Slices of explanted LNs were exposed to vaccine adjuvants and revealed responses that were not detectable in LN cell suspensions. We used this model to compare the liposome-based AS01 with its components, monophosphoryl lipid A (MPL) and QS-21, and TLR ligands. Liposomes were predominantly taken up by subcapsular sinus-lining macrophages, monocytes, and DCs. AS01 induced DC maturation and a strong proinflammatory cytokine response in intact LN slices but not in dissociated cell cultures, in contrast to R848. This suggests that the onset of the immune response to AS01 required a coordinated activation of LN cells in time and space. Consistent with the robust immune response observed in older adults with AS01-adjuvanted vaccines, the AS01 response in human LNs was independent of age, unlike the response to R848. This human LN explant model is a valuable tool for studying the mechanism of action of adjuvants in humans and for screening new formulations to streamline vaccine development.
Databáze: MEDLINE