Modulation of antigen delivery and lymph node activation in nonhuman primates by saponin adjuvant saponin/monophosphoryl lipid A nanoparticle

Parisa Yousefpour; Yiming J Zhang; Laura Maiorino; Mariane B Melo; Mariluz A Arainga Ramirez; Sidath C Kumarapperuma; Peng Xiao; Murillo Silva; Na Li; Katarzyna K Michaels; Erik Georgeson; Saman Eskandarzadeh; Michael Kubitz; Bettina Groschel; Kashif Qureshi; Jane Fontenot; Lars Hangartner; Rebecca Nedellec; J Christopher Love; Dennis R Burton; William R Schief; Francois J Villinger; Darrell J Irvine

doi:10.1093/pnasnexus/pgae529

Modulation of antigen delivery and lymph node activation in nonhuman primates by saponin adjuvant saponin/monophosphoryl lipid A nanoparticle

PNAS Nexus. 2024 Nov 25;3(12):pgae529. doi: 10.1093/pnasnexus/pgae529. eCollection 2024 Dec.

Authors

Parisa Yousefpour^{1

2

3}, Yiming J Zhang^{1

2

3

4}, Laura Maiorino^{1

2

3

5}, Mariane B Melo^{1

2

3}, Mariluz A Arainga Ramirez⁶, Sidath C Kumarapperuma⁷, Peng Xiao⁶, Murillo Silva^{1

2

3}, Na Li¹, Katarzyna K Michaels^{1

2

3

5}, Erik Georgeson^{2

3

8}, Saman Eskandarzadeh^{2

3

8}, Michael Kubitz^{2

3

8}, Bettina Groschel^{2

3

8}, Kashif Qureshi¹, Jane Fontenot⁶, Lars Hangartner^{3

8}, Rebecca Nedellec⁸, J Christopher Love^{1

2

9}, Dennis R Burton^{2

3

8

10}, William R Schief^{2

3

8

10

11}, Francois J Villinger^{6

12}, Darrell J Irvine^{1

2

3

4

5

9

13}

Affiliations

¹ Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
² Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.
³ Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA.
⁴ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁵ Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
⁶ New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA 70560, USA.
⁷ Research Imaging Institute, University of Texas Health San Antonio, San Antonio, TX 78229, USA.
⁸ Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
⁹ Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
¹⁰ IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
¹¹ Moderna Inc., Cambridge, MA 02139, USA.
¹² Department of Biology, University of Louisiana at Lafayette, New Iberia, LA 70560USA.
¹³ Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

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.

Keywords: HIV; SMNP (saponin/MPLA nanoparticles); adjuvant; nonhuman primate; vaccine.