Skip to content
2000
Volume 31, Issue 10
  • ISSN: 0929-8665
  • E-ISSN: 1875-5305

Abstract

Background

There have been great efforts in vaccine design against HIV-1 since 1981. Various approaches have been investigated, including optimized delivery systems and effective adjuvants to enhance the efficacy of selective antigen targets. In this study, we evaluated the efficiency of IMT-P8 and LDP12 cell penetrating peptides in eliciting immune responses against HIV-1 Nef-MPER-V3 fusion protein as an antigen candidate. Moreover, the potency of HP91 and HSP27 was compared as an adjuvant in female BALB/c mice through different regimens.

Methods

For this purpose, the recombinant Nef-MPER-V3, IMT-P8-Nef-MPER-V3 and LDP-Nef-MPER-V3 proteins were generated on a large scale. After mice immunization with different regimens, the secretion of antibodies, cytokines and granzyme B was evaluated by ELISA.

Results

Our results demonstrated that immunized mice receiving the Nef-MPER-V3 linked to IMT-P8 exhibited significantly higher levels of IgG compared to other groups. The IMT-P8-Nef-MPER-V3 with the Hp91 group showed the highest level of humoral response, which was significantly stronger than the LDP12 formulation using the same antigen (LDP-Nef-MPER-V3). Additionally, the combination of IMT-P8-Nef-MPER-V3 with either Hp91 or Hsp27 resulted in robust induction of IFN-γ compared to the LDP-Nef-MPER-V3 group. Furthermore, cytotoxic T lymphocyte (CTL) activation and proliferation assays indicated that IMT-P8 served as a more effective CPP, particularly when used in conjunction with the Hp91 adjuvant.

Conclusion

Altogether, the data indicated that Nef-MPER-V3 antigen in different formulations was effective in eliciting immune responses. This fusion protein has the high potency to induce both immunity arms, specifically when incorporated with IMT-P8, which showed priority to LDP12. Moreover, HP91 resulted in a greater humoral and cellular immune activation compared to HSP27. These findings suggest the potential of IMT-P8 as a superior delivery system for enhancing immune responses in vaccine development.

Loading

Article metrics loading...

/content/journals/ppl/10.2174/0109298665337811241010104557
2024-11-15
2025-01-19
Loading full text...

Full text loading...

References

  1. ChenZ. JulgB. Therapeutic vaccines for the treatment of HIV.Transl. Res.2020223617510.1016/j.trsl.2020.04.00832438074
    [Google Scholar]
  2. TrovatoM. D’ApiceL. PriscoA. De BerardinisP. HIV vaccination: A roadmap among advancements and concerns.Int. J. Mol. Sci.2018194124110.3390/ijms1904124129671786
    [Google Scholar]
  3. LarijaniM.S. SadatS.M. AmitisR. HIV-1 Immune evasion: The main obstacle toward a successful vaccine.Arch. Asthma, Allerg. Immunol.201821013015
    [Google Scholar]
  4. BayonE. MorlierasJ. Dereuddre-BosquetN. GononA. GosseL. CourantT. Le GrandR. MarcheP.N. NavarroF.P. Overcoming immunogenicity issues of HIV p24 antigen by the use of innovative nanostructured lipid carriers as delivery systems: evidences in mice and non-human primates.NPJ Vaccines2018314610.1038/s41541‑018‑0086‑030302284
    [Google Scholar]
  5. ZhaoL.P. Fiore-GartlandA. CarppL.N. CohenK.W. RouphaelN. FleursL. DintweO. ZhaoM. MoodieZ. FongY. GarrettN. HuangY. InnesC. JanesH.E. LazarusE. MichaelN.L. NitayaphanS. PitisuttithumP. Rerks-NgarmS. RobbM.L. De RosaS.C. CoreyL. GrayG.E. SeatonK.E. YatesN.L. McElrathM.J. FrahmN. TomarasG.D. GilbertP.B. Landscapes of binding antibody and T-cell responses to pox-protein HIV vaccines in Thais and South Africans.PLoS One2020151e022680310.1371/journal.pone.022680331999736
    [Google Scholar]
  6. FelberB. ValentinA. RosatiM. BergamaschiC. PavlakisG. HIV DNA vaccine: Stepwise improvements make a difference.Vaccines (Basel)20142235437910.3390/vaccines202035426344623
    [Google Scholar]
  7. M Barry S. Trial, Error, and Breakthrough: A Review of HIV Vaccine Development.J. AIDS Clin. Res.20140511
    [Google Scholar]
  8. CohenY.Z. DolinR. Novel HIV vaccine strategies: overview and perspective.Ther. Adv. Vaccines2013139911210.1177/205101361349453524757518
    [Google Scholar]
  9. GirardM.P. OsmanovS. AssossouO.M. KienyM.P. Human immunodeficiency virus (HIV) immunopathogenesis and vaccine development: A review.Vaccine201129376191621810.1016/j.vaccine.2011.06.08521718747
    [Google Scholar]
  10. van GilsM.J. SandersR.W. Broadly neutralizing antibodies against HIV-1: Templates for a vaccine.Virology20134351465610.1016/j.virol.2012.10.00423217615
    [Google Scholar]
  11. GargH. BlumenthalR. Role of HIV Gp41 mediated fusion/hemifusion in bystander apoptosis.Cell. Mol. Life Sci.200865203134314410.1007/s00018‑008‑8147‑618500445
    [Google Scholar]
  12. HartleyO. KlasseP.J. SattentauQ.J. MooreJ.P. V3: HIV’s Switch-Hitter.AIDS Res. Hum. Retroviruses200521217118910.1089/aid.2005.21.17115725757
    [Google Scholar]
  13. LarijaniM.S. PouriayevaliM.H. SadatS.M. RamezaniA. Production of recombinant HIV-1 p24-Nef protein in two forms as potential candidate vaccines in three vehicles.Curr. Drug Deliv.202017538739510.2174/156720181766620031712172832183667
    [Google Scholar]
  14. DekabanG.A. DikeakosJ.D. HIV-I Nef inhibitors: a novel class of HIV-specific immune adjuvants in support of a cure.AIDS Res. Ther.20171415310.1186/s12981‑017‑0175‑628893294
    [Google Scholar]
  15. GautamA. NandaJ.S. SamuelJ.S. KumariM. PriyankaP. BediG. NathS.K. MittalG. KhatriN. RaghavaG.P.S. Topical delivery of protein and peptide using novel cell penetrating peptide IMT-P8.Sci. Rep.2016612627810.1038/srep2627827189051
    [Google Scholar]
  16. BouazzaouiA. AbdellatifA.A.H. Vaccine delivery systems and administration routes: Advanced biotechnological techniques to improve the immunization efficacy.Vaccine X20241910050010.1016/j.jvacx.2024.10050038873639
    [Google Scholar]
  17. HaidariG. DayS. WoodM. RidgersH. CopeA.V. FleckS. YanC. ReijonenK. HannamanD. SpentzouA. HayesP. VogtA. CombadiereB. CookA. McCormackS. ShattockR.J. The safety and immunogenicity of GTU®MultiHIV DNA vaccine delivered by transcutaneous and intramuscular injection with or without electroporation in HIV-1 positive subjects on suppressive ART.Front. Immunol.201910291110.3389/fimmu.2019.0291131921170
    [Google Scholar]
  18. Ng’uniT. ChasaraC. NdhlovuZ.M. Major scientific hurdles in HIV vaccine development: Historical perspective and future directions.Front. Immunol.20201159078010.3389/fimmu.2020.59078033193428
    [Google Scholar]
  19. SkwarczynskiM. TothI. Cell-penetrating peptides in vaccine delivery: facts, challenges and perspectives.Ther. Deliv.201910846546710.4155/tde‑2019‑004231462173
    [Google Scholar]
  20. BrooksN.A. PouniotisD.S. TangC.K. ApostolopoulosV. PieterszG.A. Cell-penetrating peptides: application in vaccine delivery.Biochim. Biophys. Acta201018051253419782720
    [Google Scholar]
  21. YangJ. LuoY. ShibuM.A. TothI. SkwarczynskiaM. Cell-penetrating peptides: Efficient vectors for vaccine delivery.Curr. Drug Deliv.201916543044310.2174/156720181666619012312091530760185
    [Google Scholar]
  22. ApostolopoulosV. Vaccine delivery methods into the future.Vaccines (Basel)201642910.3390/vaccines402000927043641
    [Google Scholar]
  23. SabaghzadehS. SadatS.M. RohollahF. BolhassaniA. Effective delivery of Nef-MPER-V3 fusion protein using LDP12 cell penetrating peptide for development of preventive/therapeutic HIV-1 vaccine.Protein Pept. Lett.202027111151115810.2174/092986652766620050412140032364062
    [Google Scholar]
  24. JahedianS. SadatS.M. JavadiG.R. BolhassaniA. Production and evaluation of the properties of HIV-1-Nef-MPER-V3 fusion protein harboring IMT-P8 cell penetrating peptide.Curr. HIV Res.202018531532310.2174/1570162X1866620061215192532532193
    [Google Scholar]
  25. SasagawaT. PushkoP. SteersG. GschmeissnerS.E. Nasser HajibagheriM.A. FinchJ. CrawfordL. TommasinoM. Synthesis and assembly of virus-like particles of human papillomaviruses type 6and Type 16 in fission yeast Schizosaccharomyces pombe.Virology1995206112613510.1016/S0042‑6822(95)80027‑17831768
    [Google Scholar]
  26. VidyasagarA. WilsonN.A. DjamaliA. Heat shock protein 27 (HSP27): Biomarker of disease and therapeutic target.Fibrogenesis Tissue Repair201251710.1186/1755‑1536‑5‑722564335
    [Google Scholar]
  27. ChenC. AldarouishM. LiQ. LiuX. HanF. LiuH. QianQ. LiuH. QianQ. Triggered immune response induced by antigenic epitopes covalently linked with immunoadjuvant-pulsed dendritic cells as a promising cancer vaccine.J. Immunol. Res.2020202011010.1155/2020/396506132322595
    [Google Scholar]
  28. LarijaniM.S. RamezaniA. SadatS.M. Updated studies on the development of HIV therapeutic vaccine.Curr. HIV Res.2019172758410.2174/1570162X1766619061816060831210114
    [Google Scholar]
  29. KernéisS. LaunayO. TurbelinC. BatteuxF. HanslikT. BoëlleP.Y. Long-term immune responses to vaccination in HIV-infected patients: A systematic review and meta-analysis.Clin. Infect. Dis.20145881130113910.1093/cid/cit937
    [Google Scholar]
  30. WangQ. ZhangL. Broadly neutralizing antibodies and vaccine design against HIV-1 infection.Front. Med.2020141304210.1007/s11684‑019‑0721‑931858368
    [Google Scholar]
  31. DavoodiS. BolhassaniA. SadatS.M. IraniS. Design and in vitro delivery of HIV-1 multi-epitope DNA and peptide constructs using novel cell-penetrating peptides.Biotechnol. Lett.201941111283129810.1007/s10529‑019‑02734‑x31531750
    [Google Scholar]
  32. Sadat LarijaniM. RamezaniA. Mashhadi Abolghasem ShiraziM. BolhassaniA. PouriayevaliM.H. ShahbaziS. SadatS.M. Evaluation of transduced dendritic cells expressing HIV-1 p24-Nef antigens in HIV-specific cytotoxic T cells induction as a therapeutic candidate vaccine.Virus Res.202129819840310.1016/j.virusres.2021.19840333775753
    [Google Scholar]
  33. MilaniA. BolhassaniA. ShahbaziS. MotevalliF. SadatS.M. SoleymaniS. Small heat shock protein 27: An effective adjuvant for enhancement of HIV-1 Nef antigen-specific immunity.Immunol. Lett.2017191162210.1016/j.imlet.2017.09.00528917624
    [Google Scholar]
  34. TalebiS. BolhassaniA. SadatS.M. VahabpourR. AgiE. ShahbaziS. Hp91 immunoadjuvant: An HMGB1-derived peptide for development of therapeutic HPV vaccines.Biomed. Pharmacother.20178514815410.1016/j.biopha.2016.11.11527930979
    [Google Scholar]
  35. ZhangH. ZhangY. ZhangC. YuH. MaY. LiZ. ShiN. Recent advances of cell-penetrating peptides and their application as vectors for delivery of peptide and protein-based cargo molecules.Pharmaceutics2023158209310.3390/pharmaceutics1508209337631307
    [Google Scholar]
  36. LeeJ.E. LimH.J. LDP12, a novel cell-permeable peptide derived from L1 capsid protein of the human papillomavirus.Mol. Biol. Rep.20123921079108610.1007/s11033‑011‑0834‑y21573792
    [Google Scholar]
/content/journals/ppl/10.2174/0109298665337811241010104557
Loading
/content/journals/ppl/10.2174/0109298665337811241010104557
Loading

Data & Media loading...


  • Article Type:
    Research Article
Keyword(s): HIV-1 vaccine; HP91; HSP27; IMT-P8; LDP; Nef-MPER-V3
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test