Modulation of antigen delivery and lymph node activation in nonhuman primates by saponin adjuvant saponin/monophosphoryl lipid A nanoparticle
Name
pgae529.pdf
Description
Published version
Size
1.45 MB
Format
Adobe PDF
Checksum (MD5)
2df4dbccc89acbfb39c63b426194ef82
Author(s)
Yousefpour, Parisa
Zhang, Yiming J
Maiorino, Laura
Melo, Mariane B
Arainga Ramirez, Mariluz A
Kumarapperuma, Sidath C
Xiao, Peng
Silva, Murillo
Li, Na
Michaels, Katarzyna K
Date Issued
November 25, 2024
Journal
PNAS Nexus
Publisher
Oxford University Press
Citation
Yousefpour, Parisa, Zhang, Yiming J, Maiorino, Laura, Melo, Mariane B, Arainga Ramirez, Mariluz A et al. 2024. "Modulation of antigen delivery and lymph node activation in nonhuman primates by saponin adjuvant saponin/monophosphoryl lipid A nanoparticle." PNAS Nexus, 3 (12).
Version
Final published version
Abstract
Saponin-based vaccine adjuvants are potent in preclinical animal models and humans, but their mechanisms of action remain poorly understood. Here, using a stabilized HIV envelope trimer immunogen, we carried out studies in nonhuman primates (NHPs) comparing the most common clinical adjuvant aluminum hydroxide (alum) with saponin/monophosphoryl lipid A nanoparticles (SMNP), an immune-stimulating complex–like adjuvant. SMNP elicited substantially stronger humoral immune responses than alum, including 7-fold higher peak antigen-specific germinal center B-cell responses, 18-fold higher autologous neutralizing antibody titers, and higher levels of antigen-specific plasma and memory B cells. Positron emission tomography and computed tomography imaging in live NHPs showed that, unlike alum, SMNP promoted rapid antigen accumulation in both proximal and distal lymph nodes (LNs). SMNP also induced strong type I interferon transcriptional signatures, expansion of innate immune cells, and increased antigen-presenting cell activation in LNs. These findings indicate that SMNP promotes multiple facets of the early immune response relevant for enhanced immunity to vaccination.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Ragon Institute of MGH, MIT and Harvard
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Materials Science and Engineering
Terms of Use
Creative Commons Attribution
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1093/pnasnexus/pgae529
