The saponin monophosphoryl lipid A nanoparticle adjuvant induces dose-dependent HIV vaccine responses in nonhuman primates
Induction of durable protective immune responses is the main goal of prophylactic vaccines, and adjuvants play a role as drivers of such responses. Despite advances in vaccine strategies, development of a safe and effective HIV vaccine remains a significant challenge. Use of an appropriate adjuvant is crucial to the success of HIV vaccines. Here we assessed the saponin/MPLA nanoparticle (SMNP) adjuvant with an HIV envelope (Env) trimer, evaluating the safety and effect of multiple variables - including adjuvant dose (16-fold dose range), immunization route, and adjuvant composition - on the establishment of Env-specific memory T and B cell (TMem and BMem) responses and long-lived plasma cells in nonhuman primates (NHPs). Robust BMem were detected in all groups, but a 6-fold increase was observed in the highest- versus the lowest-SMNP-dose group. Similarly, stronger vaccine responses were induced by the highest SMNP dose in CD40L+OX40+ CD4+ TMem (11-fold), IFN-γ+ CD4+ TMem (15-fold), IL21+ CD4+ TMem (9-fold), circulating T follicular helper cells (TFH; 3.6-fold), BM plasma cells (7-fold), and binding IgG (1.3-fold). Substantial tier 2 neutralizing antibodies were only observed in the higher-SMNP-dose groups. These investigations highlight the dose-dependent potency of SMNP and its relevance for human use and next-generation vaccines.
Authors
- Mariane B. Melo (ORCID: https://orcid.org/0000-0002-0409-2454)
- Bettina Gröschel (ORCID: https://orcid.org/0000-0003-3127-5448)
- Arpan Pradhan (ORCID: https://orcid.org/0000-0003-3924-745X)
- Ashley A. Lemnios (ORCID: https://orcid.org/0000-0002-6866-6867)
- Amber Myers (ORCID: https://orcid.org/0009-0007-4115-0506)
- Lars Hangartner (ORCID: https://orcid.org/0000-0002-3165-2058)
- Sangeetha L. Sagar
- Shane Crotty (ORCID: https://orcid.org/0000-0002-6484-6262)
- Laura Maiorino (ORCID: https://orcid.org/0000-0001-8217-1337)
- Paul Lopez (ORCID: https://orcid.org/0000-0002-6437-1092)
- Gabriela Stiegler
- Ester Marina-Zárate (ORCID: https://orcid.org/0000-0003-1586-404X)
- Ivan S. Pires (ORCID: https://orcid.org/0000-0002-4035-0027)
- Dennis R. Burton (ORCID: https://orcid.org/0000-0001-6711-9864)
- William R. Schief (ORCID: https://orcid.org/0000-0002-1120-0150)
- Katarzyna Kaczmarek Michaels (ORCID: https://orcid.org/0000-0002-2525-5830)
- Eddy Sayeed
- Koen K. A. Van Rompay (ORCID: https://orcid.org/0000-0002-7375-1337)
- Sudhir Pai Kasturi (ORCID: https://orcid.org/0000-0002-6421-2040)
- Darrell J. Irvine (ORCID: https://orcid.org/0000-0002-8637-1405)
- Nathaniel I. Bloom (ORCID: https://orcid.org/0000-0002-6338-9098)
- Parham Ramezani-Rad
- Andreas Wagner
- Sam Pallerla
- Daniel Kumar
- Christopher A. Cottrell
- Iszac Burton
- Magdolna Budai
Institutions
- Oregon National Primate Research Center (US)
- Scripps Research Institute (US)
- International AIDS Vaccine Initiative (US)
- La Jolla Institute for Immunology (US)
- Howard Hughes Medical Institute (US)
- Emory University (US)
- Emory and Henry College (US)
- University of California San Diego (US)
- Polymun (Austria) (AT)
- Massachusetts Institute of Technology (US)
- University of California, Davis (US)
Publication Details
- Journal
- Journal of Clinical Investigation
- Published
- 2025-03-04
- DOI
- https://doi.org/10.1172/jci185292
- Citations
- 7
- Primary Topic
- Ginseng Biological Effects and Applications
- Type
- article
- Field-Weighted Citation Impact
- 5.64