Ramezani-Rad, .P, et al. The saponin monophosphoryl lipid A nanoparticle adjuvant induces dose-dependent HIV vaccine responses in non-human primates.
J Clin Invest, 2025 Mar 4:e185292. PMID: 40036068
The use of an appropriate adjuvant is crucial for developing an effective HIV vaccine. This study investigates the efficacy of QS-21-based saponin/monophosphoryl lipid A nanoparticle (SMNP) and AS01B adjuvants in enhancing HIV vaccine responses in non-human primates (NHPs). It evaluates safety, immunogenicity, adjuvant dosage, immunization routes, and composition effects.
The results indicate that the highest dose (400 µg) of QS-21 SMNP induced the strongest immune response compared to other adjuvants tested. Env-Specific B Cells: There was a dose-dependent increase in antigen-binding memory B cells and neutralizing antibody titers. The expansion of these cells was particularly significant after booster immunizations, demonstrating a robust humoral immune response. CD4 T Cell Responses: QS-21 SMNP induced strong Env-specific CD4 T cell responses (IFN-γ and IL-21 cytokines), particularly when administered subcutaneously rather than intramuscularly. CD8 T Cells: While CD8 T cell responses were more variable, acute Env-specific CD8 T cell responses (CD69+ IFN-γ+) were observed, particularly at higher QS-21 SMNP doses. However, memory CD8 T cells were sporadically detectable. Memory T and B Cells: Higher doses of QS-21 SMNP led to increased frequencies of Env-specific memory T and B cells, which are critical for long-term vaccine efficacy.
The study concluded that QS-21 SMNP is a potent adjuvant for enhancing immune responses to recombinant protein vaccines. It successfully induced robust and durable T and B cell memory responses in NHPs. The formulation demonstrated a favorable safety and reactogenicity profile, with higher doses (up to 400 μg) resulting in significantly stronger immune outcomes, including increased neutralizing antibodies and memory cell frequencies. The findings suggest that QS-21 SMNP holds promise as an effective adjuvant for future HIV vaccine development.
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