PMID- 38091180
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231216
IS  - 2090-5920 (Electronic)
IS  - 1687-157X (Print)
IS  - 1687-157X (Linking)
VI  - 21
IP  - 1
DP  - 2023 Dec 13
TI  - In silico analysis of HLA-1 and HLA-2 recognition of a designed recombinant human 
      papillomavirus vaccine based on L1 protein HPV subtype 45.
PG  - 167
LID - 10.1186/s43141-023-00593-8 [doi]
LID - 167
AB  - BACKGROUND: Human leukocyte antigen (HLA) can bind and present the processed 
      antigenic peptide derived from the vaccine to the T cell receptor, and this 
      capability is crucial in determining the effectivity of the vaccine to terminate 
      virus-infected cells, activate macrophages, and induce B cells to produce 
      antibodies. A recombinant vaccine candidate based on protein L1 HPV45 was 
      designed and analysed whether it is recognisable by T cells through the binding 
      of their epitopes to HLAs. METHODS: The study consisted of two parts: part one 
      was the analysis of the L1 recombinant protein binding to HLA-1 and 2 epitopes, 
      whereas part two was the distribution analysis of HPV-linked HLA allele. HLA 
      allele sets found at high frequency in the general population and in specific 
      Indonesian population were listed for the binding analysis of the recombinant L1 
      HPV45 protein. In part one, immunoepitope servers from IEDB were used to predict 
      the binding of the designed proteins to HLA alleles. The prediction method for 
      MHC-I binding prediction was the NetMHCpan EL 4.1 whilst for MHC-II binding 
      prediction was the Consensus approach. Antigenicity analysis for each peptide was 
      conducted using VaxiJen 2.0 with the threshold 1.0 to select the highly antigenic 
      peptides, and positions of these epitopes in the secondary and tertiary structure 
      of the recombinant protein were also predicted. The percent population coverage 
      of the alleles capable of binding to these epitopes worldwide was also estimated. 
      In part two, the worldwide distribution and frequency of HPV-related HLA-1 and 2 
      were studied. RESULT: Two highly antigenic peptides (EEYDLQFIF and KLKFWTVDLK) 
      were recognised by high-frequency HLA-1 alleles in both, the general and Western 
      Javanese. In addition to these two epitopes, a few more peptides are also 
      recognised by the high-frequency Western Javanese HLA-1 alleles, which are not in 
      Weiskopf's list of high-frequency HLA-1 alleles in the general population. 
      Analysis of the highly antigenic epitopes binding to HLA-DRB1 alleles in general 
      (YIKGTSANM) and Western Javanese (LRRRPTIGP) populations showed that these 
      peptide cores associate to HLA-DRB1*04, albeit the different sub-types, due to 
      the presence of different allele in each population group. Analysis of the 
      epitopes and the positive binding alleles showed on average 25.65% population 
      coverage. CONCLUSION: The recombinant vaccine candidate based on protein L1 HPV45 
      is presumed to contain highly antigenic peptides that can bind to high-frequency 
      HLA-1 and 2 alleles present in general and Western Javanese populations. It was 
      expected that the protein is capable of eliciting T cell-mediated responses in 
      both populations; however, in vitro study is needed to prove the protectiveness 
      of the designed recombinant protein.
CI  - (c) 2023. The Author(s).
FAU - Sulfianti, Asri
AU  - Sulfianti A
AD  - Centre for Vaccine and Drug Research, National Research and Innovation Agency 
      Republic of Indonesia, LAPTIAB 1, Gedung 611, Kawasan Puspiptek Serpong, 
      Tangerang Selatan, Banten, 15314, Indonesia.
FAU - Karimah, Nihayatul
AU  - Karimah N
AD  - Centre for Vaccine and Drug Research, National Research and Innovation Agency 
      Republic of Indonesia, LAPTIAB 1, Gedung 611, Kawasan Puspiptek Serpong, 
      Tangerang Selatan, Banten, 15314, Indonesia.
FAU - Nurhasanah, Astutiati
AU  - Nurhasanah A
AUID- ORCID: 0000-0003-0912-6913
AD  - Centre for Vaccine and Drug Research, National Research and Innovation Agency 
      Republic of Indonesia, LAPTIAB 1, Gedung 611, Kawasan Puspiptek Serpong, 
      Tangerang Selatan, Banten, 15314, Indonesia. astutiati.nurhasanah@brin.go.id.
LA  - eng
PT  - Journal Article
DEP - 20231213
PL  - Netherlands
TA  - J Genet Eng Biotechnol
JT  - Journal, genetic engineering & biotechnology
JID - 101317150
PMC - PMC10719189
OTO - NOTNLM
OT  - Antigenic peptides
OT  - Cervical cancer
OT  - HLA-1 alleles
OT  - HLA-2 alleles
OT  - HPV
OT  - Immuno-informatics in silico analysis
OT  - Recombinant vaccine
OT  - T cells
COIS- The authors declare that they have no competing interests.
EDAT- 2023/12/13 18:42
MHDA- 2023/12/13 18:43
PMCR- 2023/12/13
CRDT- 2023/12/13 13:32
PHST- 2022/07/11 00:00 [received]
PHST- 2023/11/06 00:00 [accepted]
PHST- 2023/12/13 18:43 [medline]
PHST- 2023/12/13 18:42 [pubmed]
PHST- 2023/12/13 13:32 [entrez]
PHST- 2023/12/13 00:00 [pmc-release]
AID - 10.1186/s43141-023-00593-8 [pii]
AID - 593 [pii]
AID - 10.1186/s43141-023-00593-8 [doi]
PST - epublish
SO  - J Genet Eng Biotechnol. 2023 Dec 13;21(1):167. doi: 10.1186/s43141-023-00593-8.