2. Academic Validation
  3. Investigation of synergistic effects of β-defensin, vesatolimod and resiquimod in increasing the potency of a therapeutic HIV-1 vaccine candidate

Investigation of synergistic effects of β-defensin, vesatolimod and resiquimod in increasing the potency of a therapeutic HIV-1 vaccine candidate

  • J Pharm Sci. 2025 Oct 9;115(1):104019. doi: 10.1016/j.xphs.2025.104019.
Seyedeh Somayeh Hosseini Alarzi 1,  Azam Bolhassani 2,  Elnaz Agi 3,  Reza Nekouian 4
Affiliations

Affiliations

  • 1 Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.
  • 2 Department of Hepatitis, AIDS and Blood-borne Diseases, Pasteur Institute of Iran, Tehran, Iran; Blood Diseases Research Center (BDRC), Iranian Comprehensive Hemophilia Care Center, Iran University of Medical Sciences (IUMS), Tehran, Iran. Electronic address: [email protected].
  • 3 Blood Diseases Research Center (BDRC), Iranian Comprehensive Hemophilia Care Center, Iran University of Medical Sciences (IUMS), Tehran, Iran.
  • 4 Pediatric Growth and Development Research Center, Institute of Endocrinology & Metabolism, Iran University of Medical Sciences, Tehran, Iran; Mehresoheila Cancer Charity, Karaj, Alborz, Iran. Electronic address: [email protected].
PMID: 41067501 DOI: 10.1016/j.xphs.2025.104019
Abstract

Improvement of therapeutic vaccination strategies is critical to control the human immunodeficiency virus-1 (HIV-1) Infection. The goal of this study is to determine the immunostimulatory effects of Toll-like Receptor (TLR) agonists including β-defensin (TLR4 Agonist), vesatolimod (GS-9620: TLR7 Agonist) and resiquimod (R848: TLR7/8 agonist) as individual or combined with the Nefmut-Tat antigen candidate in BALB/c mice. The results of immune responses for groups receiving the recombinant Nefmut-Tat protein (∼ 35 kDa) and the recombinant β-defensin-Nefmut-Tat protein (∼ 45 kDa) showed that the linkage of β-defensin to Nefmut-Tat protein could significantly increase the secretion of IFN-γ, TNF-α and Granzyme B. Furthermore, the highest levels of IFN-γ, TNF-α and Granzyme B was observed in group receiving β-defensin-Nefmut-Tat protein + GS-9620 + R848 regimen indicating the potent synergistic effects of TLR agonists on induction of cellular immunity (i.e., stimulation of T-helper 1 cells and cytotoxic T lymphocytes). This regimen could significantly induce IFN-γ and TNF-α in splenocytes infected with single-cycle replicable (SCR) HIV-1 in vitro, as well. It was interesting that no significant differences in TNF-α and Granzyme B secretion were observed between groups receiving β-defensin-Nefmut-Tat protein + GS-9620 and β-defensin-Nefmut-Tat protein + R848; although group receiving β-defensin-Nefmut-Tat protein + R848 could significantly induce IFN-γ secretion in uninfected and infected splenocytes compared to group receiving β-defensin-Nefmut-Tat protein + GS-9620. These findings demonstrated that the simultaneous use of TLR 4, 7 and 8 agonists could improve and maintain cellular immunity against SCR HIV-1 Infection suggesting an effective approach for eradication of latent HIV reservoir.

Keywords

Adjuvants; HIV-1; Nef(mut)-Tat antigen; Resiquimod; Toll-like receptor agonists; Vesatolimod; Β-defensin.

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