
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.08.28.608716
preprint
1
Article
Modulation of antigen delivery and lymph node activation in non-human primates by saponin adjuvant SMNP
Yousefpour Parisa http://orcid.org/0000-0003-0431-8131

J. Zhang Yiming http://orcid.org/0000-0002-8102-3815

Maiorino Laura
Melo Mariane B.
Arainga Ramirez Mariluz A.
Kumarapperuma Sidath C.
Xiao Peng
Silva Murillo
Li Na
Michaels Katarzyna K.
Georgeson Erik
Eskandarzadeh Saman
Kubitz Michael
Groschel Bettina
Qureshi Kashif
Fontenot Jane
Hangartner Lars
Nedellec Rebecca
Love J. Christopher
Burton Dennis R.
Schief William R.
Villinger Francois J.
Irvine Darrell J. http://orcid.org/0000-0002-8637-1405

28 8 2024
2024.08.28.608716https://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
http://biorxiv.org/lookup/doi/10.1101/2024.08.28.608716
nihpp-2024.08.28.608716.pdf
SUMMARY

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 non-human primates (NHPs) comparing the most common clinical adjuvant alum with Saponin/MPLA Nanoparticles (SMNP), a novel ISCOMs-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. PET-CT 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.
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