Current Peptide and Protein Candidates Challenging HIV Therapy beyond the Vaccine Era
Abstract
:1. Introduction
2. HIV-1 Vaccine Development
3. Alternative HIV Gene Therapies
3.1. Adoptive T Cell Transfer and Immunotherapy
3.2. Peptides and Proteins for HIV Therapy
3.2.1. The HIV-1 Entry Inhibitors
3.2.2. The HIV-1 Integration Inhibitors
3.2.3. The HIV-1 Assembly Inhibitors
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Vaccines | Types | Results | Immunogens | References |
---|---|---|---|---|
VAX003 | Passive vaccine | No vaccine efficacy | gp120 of HIV-1 subtypes B and E (strains MN and A244) | [36] |
VAX004 | Passive vaccine | No vaccine efficacy | gp120 of HIV-1 subtypes B (strains MN and GNE8) | [37] |
STEP (HVTN502) | Active vaccine: T-cell activation | No vaccine efficacy, increased HIV infection rates | Subtype B, MRKAd5-gag/pol/nef | [43] |
Phambili (HVTN503) | Active vaccine: T-cell activation | No vaccine efficacy | Subtype B, MRKAd5-gag/pol/nef | [44] |
RV114 | Passive and active vaccine | Estimated efficacy 31% at 42 months | Prime: subtype B and A/E ALVAC-HIV-gag-pr-gp41-gp120 Boost: subtypes B and E AIDSVAX B/E (gp120 subunit proteins) | [40,41] |
Peptides or Proteins | Types | Targets | Efficacy | Clinical Trials | References |
---|---|---|---|---|---|
Immunoglobulin-Based Molecules | |||||
GPI-scFv X5 | Entry inhibitor | CCR5, CXCR4 co-receptor | Protects CD4+ T cells from R5, X4, and dual-tropic HIV-1; can be immunogenic and generate HIV-1 mutants in long-term infections | Preclinical trial | [54] |
scFv MF85 | Assembly inhibitor | HIV-1 p24 | High binding activity towards p24 antigen; not suitable for protein folding in cytoplasm | Ongoing research | [85] |
Non-Immunoglobulin-Based Molecules | |||||
gp120-specific DARPin | Entry inhibitor | HIV-1 gp120 | Target gp120 with high affinity and specificity; would drive HIV-1 mutation in HIV-1 Envelope | Ongoing research | [57] |
CD4-specific DARPin | Entry inhibitor | CD4 molecule | Targets CD4 with high affinity to inhibit HIV entry; rapidly cleared from the circulation | Ongoing research | [58,59] |
C-C ligand 5 (CCL5) | Entry inhibitor | CCR5 co-receptor | Binds to CCR5 molecule to inhibit HIV entry | Ongoing research | [60] |
PSC-RANTES | Entry inhibitor | CCR5 co-receptor | Inhibits HIV-1 vaginal transmission in monkey model | Preclinical trial | [61] |
T20 | Fusion inhibitor | HIV-1 gp41, NHR | Antiviral peptide approved by FDA for inhibiting HIV-1 entry; has to inject twice daily and can develop HIV-1-resistant strains | Phase II | [65] |
C46 | Fusion inhibitor | HIV-1 gp41, NHR | More effective than T20; can develop HIV-1-resistant strains | Phase I/II | [66,67,68] |
RIN-25 | Integration inhibitor | HIV-1 IN | Exhibits IN-inhibitory activity | Ongoing research | [72] |
2LTRZFP | Integration inhibitor | HIV-1 LTR | Targets HIV-1 2LTR to block HIV-1 integration | Ongoing research | [73,74] |
Peptide competitor, HKWPWW | Assembly inhibitor | HIV-1 ψ-RNA | Inhibits HIV-1 assembly by binding to packaging signal of genomic RNA | Ongoing research | [80,81,82] |
Ankyrin repeat protein, AnkGAG1D4 | Assembly inhibitor | HIV-1 p24 | Binds to N-terminal of HIV-1 capsid, limited effects in HIV-1 heavy infection | Ongoing research | [74,86] |
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Chupradit, K.; Moonmuang, S.; Nangola, S.; Kitidee, K.; Yasamut, U.; Mougel, M.; Tayapiwatana, C. Current Peptide and Protein Candidates Challenging HIV Therapy beyond the Vaccine Era. Viruses 2017, 9, 281. https://doi.org/10.3390/v9100281
Chupradit K, Moonmuang S, Nangola S, Kitidee K, Yasamut U, Mougel M, Tayapiwatana C. Current Peptide and Protein Candidates Challenging HIV Therapy beyond the Vaccine Era. Viruses. 2017; 9(10):281. https://doi.org/10.3390/v9100281
Chicago/Turabian StyleChupradit, Koollawat, Sutpirat Moonmuang, Sawitree Nangola, Kuntida Kitidee, Umpa Yasamut, Marylène Mougel, and Chatchai Tayapiwatana. 2017. "Current Peptide and Protein Candidates Challenging HIV Therapy beyond the Vaccine Era" Viruses 9, no. 10: 281. https://doi.org/10.3390/v9100281