Advertisement
ResearchIn-Press PreviewImmunologyVaccines Open Access | 10.1172/JCI174144
1Centre for Virus Research, Westmead Institute for Medical Research, University of Sydney, Sydney, Australia
2Research and Education Network, Western Sydney Local Health District, Sydney, Australia
3The Westmead Breast Cancer Institute, Westmead Hospital, University of Sydney, Sydney, Australia
4GSK, Rixensart, Belgium
5Center of Vaccinology, Department of Pathology and Immunology, Faculty of M, University of Geneva, Geneva, Switzerland
Find articles by Stylianou, V. in: JCI | PubMed | Google Scholar
1Centre for Virus Research, Westmead Institute for Medical Research, University of Sydney, Sydney, Australia
2Research and Education Network, Western Sydney Local Health District, Sydney, Australia
3The Westmead Breast Cancer Institute, Westmead Hospital, University of Sydney, Sydney, Australia
4GSK, Rixensart, Belgium
5Center of Vaccinology, Department of Pathology and Immunology, Faculty of M, University of Geneva, Geneva, Switzerland
Find articles by Bertram, K. in: JCI | PubMed | Google Scholar
1Centre for Virus Research, Westmead Institute for Medical Research, University of Sydney, Sydney, Australia
2Research and Education Network, Western Sydney Local Health District, Sydney, Australia
3The Westmead Breast Cancer Institute, Westmead Hospital, University of Sydney, Sydney, Australia
4GSK, Rixensart, Belgium
5Center of Vaccinology, Department of Pathology and Immunology, Faculty of M, University of Geneva, Geneva, Switzerland
Find articles by Vo, V. in: JCI | PubMed | Google Scholar
1Centre for Virus Research, Westmead Institute for Medical Research, University of Sydney, Sydney, Australia
2Research and Education Network, Western Sydney Local Health District, Sydney, Australia
3The Westmead Breast Cancer Institute, Westmead Hospital, University of Sydney, Sydney, Australia
4GSK, Rixensart, Belgium
5Center of Vaccinology, Department of Pathology and Immunology, Faculty of M, University of Geneva, Geneva, Switzerland
Find articles by Dunn, E. in: JCI | PubMed | Google Scholar
1Centre for Virus Research, Westmead Institute for Medical Research, University of Sydney, Sydney, Australia
2Research and Education Network, Western Sydney Local Health District, Sydney, Australia
3The Westmead Breast Cancer Institute, Westmead Hospital, University of Sydney, Sydney, Australia
4GSK, Rixensart, Belgium
5Center of Vaccinology, Department of Pathology and Immunology, Faculty of M, University of Geneva, Geneva, Switzerland
Find articles by Baharlou, H. in: JCI | PubMed | Google Scholar
1Centre for Virus Research, Westmead Institute for Medical Research, University of Sydney, Sydney, Australia
2Research and Education Network, Western Sydney Local Health District, Sydney, Australia
3The Westmead Breast Cancer Institute, Westmead Hospital, University of Sydney, Sydney, Australia
4GSK, Rixensart, Belgium
5Center of Vaccinology, Department of Pathology and Immunology, Faculty of M, University of Geneva, Geneva, Switzerland
Find articles by Terre, D. in: JCI | PubMed | Google Scholar
1Centre for Virus Research, Westmead Institute for Medical Research, University of Sydney, Sydney, Australia
2Research and Education Network, Western Sydney Local Health District, Sydney, Australia
3The Westmead Breast Cancer Institute, Westmead Hospital, University of Sydney, Sydney, Australia
4GSK, Rixensart, Belgium
5Center of Vaccinology, Department of Pathology and Immunology, Faculty of M, University of Geneva, Geneva, Switzerland
Find articles by Elhindi, J. in: JCI | PubMed | Google Scholar |
1Centre for Virus Research, Westmead Institute for Medical Research, University of Sydney, Sydney, Australia
2Research and Education Network, Western Sydney Local Health District, Sydney, Australia
3The Westmead Breast Cancer Institute, Westmead Hospital, University of Sydney, Sydney, Australia
4GSK, Rixensart, Belgium
5Center of Vaccinology, Department of Pathology and Immunology, Faculty of M, University of Geneva, Geneva, Switzerland
Find articles by Elder, E. in: JCI | PubMed | Google Scholar
1Centre for Virus Research, Westmead Institute for Medical Research, University of Sydney, Sydney, Australia
2Research and Education Network, Western Sydney Local Health District, Sydney, Australia
3The Westmead Breast Cancer Institute, Westmead Hospital, University of Sydney, Sydney, Australia
4GSK, Rixensart, Belgium
5Center of Vaccinology, Department of Pathology and Immunology, Faculty of M, University of Geneva, Geneva, Switzerland
Find articles by French, J. in: JCI | PubMed | Google Scholar
1Centre for Virus Research, Westmead Institute for Medical Research, University of Sydney, Sydney, Australia
2Research and Education Network, Western Sydney Local Health District, Sydney, Australia
3The Westmead Breast Cancer Institute, Westmead Hospital, University of Sydney, Sydney, Australia
4GSK, Rixensart, Belgium
5Center of Vaccinology, Department of Pathology and Immunology, Faculty of M, University of Geneva, Geneva, Switzerland
Find articles by Meybodi, F. in: JCI | PubMed | Google Scholar
1Centre for Virus Research, Westmead Institute for Medical Research, University of Sydney, Sydney, Australia
2Research and Education Network, Western Sydney Local Health District, Sydney, Australia
3The Westmead Breast Cancer Institute, Westmead Hospital, University of Sydney, Sydney, Australia
4GSK, Rixensart, Belgium
5Center of Vaccinology, Department of Pathology and Immunology, Faculty of M, University of Geneva, Geneva, Switzerland
Find articles by Temmerman, S. in: JCI | PubMed | Google Scholar
1Centre for Virus Research, Westmead Institute for Medical Research, University of Sydney, Sydney, Australia
2Research and Education Network, Western Sydney Local Health District, Sydney, Australia
3The Westmead Breast Cancer Institute, Westmead Hospital, University of Sydney, Sydney, Australia
4GSK, Rixensart, Belgium
5Center of Vaccinology, Department of Pathology and Immunology, Faculty of M, University of Geneva, Geneva, Switzerland
Find articles by Didierlaurent, A. in: JCI | PubMed | Google Scholar
1Centre for Virus Research, Westmead Institute for Medical Research, University of Sydney, Sydney, Australia
2Research and Education Network, Western Sydney Local Health District, Sydney, Australia
3The Westmead Breast Cancer Institute, Westmead Hospital, University of Sydney, Sydney, Australia
4GSK, Rixensart, Belgium
5Center of Vaccinology, Department of Pathology and Immunology, Faculty of M, University of Geneva, Geneva, Switzerland
Find articles by Coccia, M. in: JCI | PubMed | Google Scholar
1Centre for Virus Research, Westmead Institute for Medical Research, University of Sydney, Sydney, Australia
2Research and Education Network, Western Sydney Local Health District, Sydney, Australia
3The Westmead Breast Cancer Institute, Westmead Hospital, University of Sydney, Sydney, Australia
4GSK, Rixensart, Belgium
5Center of Vaccinology, Department of Pathology and Immunology, Faculty of M, University of Geneva, Geneva, Switzerland
Find articles by Sandgren, K. in: JCI | PubMed | Google Scholar |
1Centre for Virus Research, Westmead Institute for Medical Research, University of Sydney, Sydney, Australia
2Research and Education Network, Western Sydney Local Health District, Sydney, Australia
3The Westmead Breast Cancer Institute, Westmead Hospital, University of Sydney, Sydney, Australia
4GSK, Rixensart, Belgium
5Center of Vaccinology, Department of Pathology and Immunology, Faculty of M, University of Geneva, Geneva, Switzerland
Find articles by Cunningham, A. in: JCI | PubMed | Google Scholar |
Published September 24, 2024 - More info
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 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 MPL and QS-21, and TLR ligands. Liposomes were predominantly taken up by subcapsular sinus-lining macrophages, monocytes and dendritic cells. AS01 induced dendritic cell maturation and a strong pro-inflammatory cytokine response in intact LN slices but not in dissociated cell cultures, in contrast to R848. This suggests the onset of the immune response to AS01 requires 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 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.