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PreprintCited by 1vaccines and immunoinformatics approachesImmunotherapy and Immune ResponsesCancer Immunotherapy and Biomarkers

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Identification and evaluation of tumor pyroptosis-associated antigens for design a vaccine candidate against lung cancer

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Nguyen, Truc Ly, Kim, Heebal·2024·Scientific Reports
DOI 10.21203/rs.3.rs-5329441/v1PMC PMC13009229

Preprint — published as 10.1038/s41598-024-84792-4

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Abstract

Lung cancer is the leading cause of cancer-related mortality worldwide, necessitating the development of new treatment strategies. This study aims to design a novel multi-epitope vaccine targeting pyroptosis-associated proteins (CARD8, NAIP, NLRP1, and NLRP3) using immunoinformatics. T-cell and B-cell epitopes were identified from these proteins and assessed for antigenicity, non-toxicity, and immune-stimulatory potential. Fifteen epitopes with high scores were selected and combined with suitable adjuvants and linkers to form a vaccine construct. The three-dimensional structure of the vaccine was predicted, refined, and validated through molecular modeling techniques. Molecular dynamics simulations confirmed the vaccine's structural stability and flexibility under physiological conditions. Furthermore, in silico immune simulations suggested that the vaccine could elicit strong humoral and cellular immune responses, including high antibody production and robust T-helper and T-cytotoxic cell activation. These findings suggest the vaccine’s potential to generate long-term immunity. While computational predictions are promising, in vitro and in vivo validation is required to confirm the vaccine’s efficacy and safety. This study highlights the potential of targeting pyroptosis pathways in lung cancer and underscores the value of computational tools in accelerating vaccine design. If proven effective in experimental settings, this vaccine could contribute to more effective lung cancer immunotherapies, offering a new avenue for treatment in a disease with limited options.

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Metadata

Authors
Nguyen, T. L., & Kim, H.
Affiliations
Seoul National University (KR)
Corresponding author
Kim, Heebal
ORCID
Kim, Heebal
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2024-11-05
Volume
16
Issue
1
ISSN
2045-2322 (ISSN-L)
DOI
10.21203/rs.3.rs-5329441/v1
PMC
PMC13009229
OpenAlex
W7139133375
Cited by
1
References
1
Citations by year
2026: 1
FWCI
2.03
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Seoul National University Open Repository (Seoul National University) (submittedVersion)
Funders
  • Seoul National University
  • Animal and Plant Quarantine Agency
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords
lung cancer, pyroptosis, multi-epitope vaccine, CARD8, NAIP, NLRP1, NLRP3, T cell epitopes, B-cell epitopes, vaccine adjuvants, TLR activation, immunogenicity prediction, codon optimization
MeSH terms
Pyroptosis, Immunoinformatics, Protein Subunit Vaccines, Animals, Antigens, Neoplasm, Humans, Lung Neoplasms, Epitopes, T-Lymphocyte, Epitopes, B-Lymphocyte, Cancer Vaccines, Molecular Dynamics Simulation, Molecular Docking Simulation

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