Retrospective Computational and Immunoinformatics Validation of Clinically Evaluated Necator americanus Protein Vaccine Candidates: Na-APR-1, Na-GST-1, and Na-ASP-2
- 1University of Buea
Abstract
Hookworm disease, primarily caused by Necator americanus, affects about 472 million people worldwide and contributes substantially to global disease burden, yet no approved vaccine is currently available. The clinical failure of Na-ASP-2 protein due to IgE-mediated hypersensitivity highlights the need for safe, immunogenic hookworm vaccines and emphasizes the importance of rigorous pre-clinical safety screening. Using an integrated immunoinformatics approach, this work retrospectively evaluated the safety and immunogenicity of three clinical hookworm protein vaccine candidates: Na-APR-1, Na-GST-1, and Na-ASP-2. Toxigenicity and allergenicity predictions correctly identified Na-ASP-2 as toxigenic and allergenic, consistent with its documented clinical failure, while Na-APR-1 exhibited a favourable safety profile; Na-GST-1 showed inconsistent allergenicity signals warranting experimental validation. Comprehensive epitope prediction identified abundant CTL, HTL, B-cell, and cytokine-inducing epitopes across all candidates, with Na-APR-1 demonstrating the broadest epitope repertoire. HLA population coverage analysis indicated broad global applicability across endemic regions. Molecular docking with TLR4 revealed that all antigens interact with the receptor with binding energies more favourable than the positive control agonist, with Na-GST-1 and Na-APR-1 displaying the strongest predicted affinities. Normal mode analyses predicted stable antigen-TLR4 complex dynamics across all candidates. Immune simulations predicted robust, memory-driven humoral and cellular responses for Na-APR-1 and Na-ASP-2, while Na-GST-1 showed markedly attenuated simulated immunogenicity despite favourable structural and receptor-binding characteristics. These findings support continued clinical development of Na-APR-1, highlight unresolved immunogenic discordances for Na-GST-1 requiring experimental verification, and collectively provide a validated computational framework for advancing rational hookworm vaccine design.
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BibTeX
@misc{tangan2026retrospective,
title = {{Retrospective Computational and Immunoinformatics Validation of Clinically Evaluated Necator americanus Protein Vaccine Candidates: Na-APR-1, Na-GST-1, and Na-ASP-2}},
author = {Y. A. S. Tangan and G. T. Nchanji and M. N. Moyeh and T. M. Efeti and M. S. Lahngong and K. P. Nkineh and A. B. Ayuk and J. E. Engarimbi and C. R. Achungu and C. M. Shintouo and D. M. Berinyuy and N. E. Yaah and B. N. Yengo and T. B. Muyer and K. Y. Gwei and B. T. Tebo and N. G. Nyah and S. M. Ghogomu and R. A. Shey},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.02.748823},
url = {https://www.biorxiv.org/content/10.64898/2026.09.02.748823v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Retrospective Computational and Immunoinformatics Validation of Clinically Evaluated Necator americanus Protein Vaccine Candidates: Na-APR-1, Na-GST-1, and Na-ASP-2
AU - Y. A. S. Tangan
AU - G. T. Nchanji
AU - M. N. Moyeh
AU - T. M. Efeti
AU - M. S. Lahngong
AU - K. P. Nkineh
AU - A. B. Ayuk
AU - J. E. Engarimbi
AU - C. R. Achungu
AU - C. M. Shintouo
AU - D. M. Berinyuy
AU - N. E. Yaah
AU - B. N. Yengo
AU - T. B. Muyer
AU - K. Y. Gwei
AU - B. T. Tebo
AU - N. G. Nyah
AU - S. M. Ghogomu
AU - R. A. Shey
PY - 2026
DA - 2026/09/02
PB - bioRxiv
DO - 10.64898/2026.09.02.748823
UR - https://www.biorxiv.org/content/10.64898/2026.09.02.748823v1
AB - Hookworm disease, primarily caused by Necator americanus, affects about 472 million people worldwide and contributes substantially to global disease burden, yet no approved vaccine is currently available. The clinical failure of Na-ASP-2 protein due to IgE-mediated hypersensitivity highlights the need for safe, immunogenic hookworm vaccines and emphasizes the importance of rigorous pre-clinical safety screening. Using an integrated immunoinformatics approach, this work retrospectively evaluated the safety and immunogenicity of three clinical hookworm protein vaccine candidates: Na-APR-1, Na-GST-1, and Na-ASP-2. Toxigenicity and allergenicity predictions correctly identified Na-ASP-2 as toxigenic and allergenic, consistent with its documented clinical failure, while Na-APR-1 exhibited a favourable safety profile; Na-GST-1 showed inconsistent allergenicity signals warranting experimental validation. Comprehensive epitope prediction identified abundant CTL, HTL, B-cell, and cytokine-inducing epitopes across all candidates, with Na-APR-1 demonstrating the broadest epitope repertoire. HLA population coverage analysis indicated broad global applicability across endemic regions. Molecular docking with TLR4 revealed that all antigens interact with the receptor with binding energies more favourable than the positive control agonist, with Na-GST-1 and Na-APR-1 displaying the strongest predicted affinities. Normal mode analyses predicted stable antigen-TLR4 complex dynamics across all candidates. Immune simulations predicted robust, memory-driven humoral and cellular responses for Na-APR-1 and Na-ASP-2, while Na-GST-1 showed markedly attenuated simulated immunogenicity despite favourable structural and receptor-binding characteristics. These findings support continued clinical development of Na-APR-1, highlight unresolved immunogenic discordances for Na-GST-1 requiring experimental verification, and collectively provide a validated computational framework for advancing rational hookworm vaccine design.
ER -