Modulation of antigen delivery and lymph node activation in non-human primates by saponin adjuvant SMNP.

Autor:	Yousefpour P; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University; Cambridge, MA 02139 USA.; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute; La Jolla, CA 92037 USA., Zhang YJ; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University; Cambridge, MA 02139 USA.; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute; La Jolla, CA 92037 USA.; Department of Biological Engineering, Massachusetts Institute of Technology; Cambridge, MA 02139 USA., Maiorino L; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University; Cambridge, MA 02139 USA.; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute; La Jolla, CA 92037 USA.; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA., Melo MB; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University; Cambridge, MA 02139 USA.; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute; La Jolla, CA 92037 USA., Arainga Ramirez MA; New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA 70560, USA., Kumarapperuma SC; Research Imaging Institute, University of Texas Health San Antonio, San Antonio, TX, 78229, USA., Xiao P; New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA 70560, USA., Silva M; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University; Cambridge, MA 02139 USA.; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute; La Jolla, CA 92037 USA., Li N; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Michaels KK; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University; Cambridge, MA 02139 USA.; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute; La Jolla, CA 92037 USA.; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA., Georgeson E; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University; Cambridge, MA 02139 USA.; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute; La Jolla, CA 92037 USA.; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA., Eskandarzadeh S; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University; Cambridge, MA 02139 USA.; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute; La Jolla, CA 92037 USA.; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA., Kubitz M; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University; Cambridge, MA 02139 USA.; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute; La Jolla, CA 92037 USA.; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA., Groschel B; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University; Cambridge, MA 02139 USA.; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute; La Jolla, CA 92037 USA.; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA., Qureshi K; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Fontenot J; New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA 70560, USA., Hangartner L; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute; La Jolla, CA 92037 USA.; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA., Nedellec R; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA., Love JC; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University; Cambridge, MA 02139 USA.; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Burton DR; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University; Cambridge, MA 02139 USA.; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute; La Jolla, CA 92037 USA.; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA., Schief WR; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University; Cambridge, MA 02139 USA.; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute; La Jolla, CA 92037 USA.; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.; Moderna Inc., Cambridge, MA 02139, USA., Villinger FJ; New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA 70560, USA.; Department of Biology, University of Louisiana at Lafayette, New Iberia, LA 70560 USA., Irvine DJ; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University; Cambridge, MA 02139 USA.; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute; La Jolla, CA 92037 USA.; Department of Biological Engineering, Massachusetts Institute of Technology; Cambridge, MA 02139 USA.; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Aug 28. Date of Electronic Publication: 2024 Aug 28.
DOI:	10.1101/2024.08.28.608716
Abstrakt:	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. Competing Interests: Declaration of interests DJI is an inventor on a patent application filed on SMNP by the Massachusetts Institute of Technology (International Patent Application No. US20230157967A1). WRS is an inventor on patents related to the MD39 HIV Env trimer immunogen. The other authors have no competing financial interests in relation to this work.
Databáze:	MEDLINE
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