PMID- 37940672
OWN - NLM
STAT- MEDLINE
DCOM- 20231110
LR  - 20231111
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 13
IP  - 1
DP  - 2023 Nov 8
TI  - Engineering and design of promising T-cell-based multi-epitope vaccine candidates 
      against leishmaniasis.
PG  - 19421
LID - 10.1038/s41598-023-46408-1 [doi]
LID - 19421
AB  - Cutaneous leishmaniasis (CL) is a very common parasitic infection in subtropical 
      areas worldwide. Throughout decades, there have been challenges in vaccine design 
      and vaccination against CL. The present study introduced novel T-cell-based 
      vaccine candidates containing IFN-gamma Inducing epitopic fragments from Leishmania 
      major (L. major) glycoprotein 46 (gp46), cathepsin L-like and B-like proteases, 
      histone H2A, glucose-regulated protein 78 (grp78) and stress-inducible protein 1 
      (STI-1). For this aim, top-ranked human leukocyte antigen (HLA)-specific, IFN-gamma 
      Inducing, antigenic, CD(4)(+) and CD(8)(+) binders were highlighted. Four vaccine 
      candidates were generated using different spacers (AAY, GPGPG, GDGDG) and 
      adjuvants (RS-09 peptide, human IFN-gamma, a combination of both, Mycobacterium 
      tuberculosis Resuscitation promoting factor E (RpfE)). Based on the immune 
      simulation profile, those with RS-09 peptide (Leish-App) and RpfE (Leish-Rpf) 
      elicited robust immune responses and their tertiary structure were further 
      refined. Also, molecular docking of the selected vaccine models with the human 
      toll-like receptor 4 showed proper interactions, particularly for Leish-App, for 
      which molecular dynamics simulations showed a stable connection with TLR-4. Upon 
      codon optimization, both models were finally ligated into the pET28a( +) vector. 
      In conclusion, two potent multi-epitope vaccine candidates were designed against 
      CL and evaluated using comprehensive in silico methods, while further wet 
      experiments are, also, recommended.
CI  - (c) 2023. The Author(s).
FAU - Basmenj, Esmaeil Roohparvar
AU  - Basmenj ER
AD  - Biophysics Department, Faculty of Biological Sciences, Tarbiat Modares 
      University, Tehran, Iran.
FAU - Arastonejad, Mahshid
AU  - Arastonejad M
AD  - Department of Human and Molecular Genetics, Virginia Commonwealth University, 
      Richmond, VA, USA.
FAU - Mamizadeh, Mina
AU  - Mamizadeh M
AD  - Department of Dermatology, School of Medicine, Ilam University of Medical 
      Sciences, Ilam, Iran.
AD  - Zoonotic Diseases Research Center, Ilam University of Medical Sciences, Ilam, 
      Iran.
FAU - Alem, Mahsa
AU  - Alem M
AD  - Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, 
      Urmia, Iran.
FAU - KhalatbariLimaki, Mahdi
AU  - KhalatbariLimaki M
AD  - Department of Pharmaceutical Sciences, School of Pharmacy, Guilan University of 
      Medical Sciences, Rasht, Iran.
FAU - Ghiabi, Shadan
AU  - Ghiabi S
AD  - Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad 
      University, Tehran, Iran.
FAU - Khamesipour, Ali
AU  - Khamesipour A
AD  - Center for Research and Training in Skin Diseases and Leprosy, Tehran University 
      of Medical Sciences, Tehran, 14155-6383, Iran.
FAU - Majidiani, Hamidreza
AU  - Majidiani H
AD  - Healthy Aging Research Centre, Neyshabur University of Medical Sciences, 
      Neyshabur, Iran. majidianih1@nums.ac.ir.
AD  - Department of Basic Medical Sciences, Neyshabur University of Medical Sciences, 
      Neyshabur, Iran. majidianih1@nums.ac.ir.
FAU - Shams, Morteza
AU  - Shams M
AD  - Zoonotic Diseases Research Center, Ilam University of Medical Sciences, Ilam, 
      Iran. shamsimorteza55@gmail.com.
FAU - Irannejad, Hamid
AU  - Irannejad H
AD  - Department of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of 
      Medical Sciences, Sari, Iran.
AD  - Pharmaceutical Sciences Research Center, Mazandaran University of Medical 
      Sciences, Sari, Iran.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231108
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Vaccines)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 0 (Vaccines, Subunit)
RN  - 0 (Epitopes, B-Lymphocyte)
SB  - IM
MH  - Humans
MH  - Epitopes, T-Lymphocyte
MH  - *Leishmaniasis, Visceral/parasitology
MH  - Molecular Docking Simulation
MH  - T-Lymphocytes
MH  - *Vaccines
MH  - *Leishmaniasis, Cutaneous
MH  - Interferon-gamma
MH  - Computational Biology
MH  - Vaccines, Subunit
MH  - Epitopes, B-Lymphocyte
PMC - PMC10632461
COIS- The authors declare no competing interests.
EDAT- 2023/11/09 00:42
MHDA- 2023/11/10 06:45
PMCR- 2023/11/08
CRDT- 2023/11/08 23:21
PHST- 2023/07/13 00:00 [received]
PHST- 2023/10/31 00:00 [accepted]
PHST- 2023/11/10 06:45 [medline]
PHST- 2023/11/09 00:42 [pubmed]
PHST- 2023/11/08 23:21 [entrez]
PHST- 2023/11/08 00:00 [pmc-release]
AID - 10.1038/s41598-023-46408-1 [pii]
AID - 46408 [pii]
AID - 10.1038/s41598-023-46408-1 [doi]
PST - epublish
SO  - Sci Rep. 2023 Nov 8;13(1):19421. doi: 10.1038/s41598-023-46408-1.