TY - JOUR
T1 - Modulation of antigen delivery and lymph node activation in nonhuman primates by saponin adjuvant saponin/monophosphoryl lipid A nanoparticle
AU - Yousefpour, Parisa
AU - Zhang, Yiming J.
AU - Maiorino, Laura
AU - Melo, Mariane B.
AU - Arainga Ramirez, Mariluz A.
AU - Kumarapperuma, Sidath C.
AU - Xiao, Peng
AU - Silva, Murillo
AU - Li, Na
AU - Michaels, Katarzyna K.
AU - Georgeson, Erik
AU - Eskandarzadeh, Saman
AU - Kubitz, Michael
AU - Groschel, Bettina
AU - Qureshi, Kashif
AU - Fontenot, Jane
AU - Hangartner, Lars
AU - Nedellec, Rebecca
AU - Christopher Love, J.
AU - Burton, Dennis R.
AU - Schief, William R.
AU - Villinger, Francois J.
AU - Irvine, Darrell J.
N1 - Publisher Copyright:
© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.
PY - 2024/12/1
Y1 - 2024/12/1
N2 - 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.
AB - 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.
KW - HIV
KW - SMNP (saponin/MPLA nanoparticles)
KW - adjuvant
KW - nonhuman primate
KW - vaccine
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UR - http://www.scopus.com/inward/citedby.url?scp=85211996451&partnerID=8YFLogxK
U2 - 10.1093/pnasnexus/pgae529
DO - 10.1093/pnasnexus/pgae529
M3 - Article
C2 - 39677368
AN - SCOPUS:85211996451
SN - 2752-6542
VL - 3
JO - PNAS Nexus
JF - PNAS Nexus
IS - 12
M1 - pgae529
ER -