Preprint
Retrospective Computational and Immunoinformatics Validation of Clinically Evaluated Necator americanus Protein Vaccine Candidates: Na-APR-1, Na-GST-1, and Na-ASP-2
bioRxiv : the preprint server for biology
08 Sep 2026
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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Details
- Title
- Retrospective Computational and Immunoinformatics Validation of Clinically Evaluated Necator americanus Protein Vaccine Candidates: Na-APR-1, Na-GST-1, and Na-ASP-2
- Creators
- Yanick Aqua Stong Tangan - University of BueaG Takop Nchanji - University of BueaMarcel Nyuylam Moyeh - University of BueaTeke Mary Efeti - University of BueaLahngong Methodius Shinyuy - University of BueaKwi Pilate Nkineh - London School of Hygiene & Tropical MedicineAbey Blessings Ayuk - University of BueaJunior Ekunidi Engarimbi - University of BueaChe Roland Achungu - Florence Nightingale Higher institute of Health and Biomedical Sciences (Cameroon, Bamenda)Cabirou Mounchili Shintouo - University of BueaDulandzev Melvis Berinyuy - University of BueaNtang Emmaculate Yaah - University of BueaBernis Neneyoh Yengo - Drexel UniversityTamnjong Beltine Muyer - University of BueaKetura Yaje Gwei - University of BueaBrinate Teke Tebo - University of BueaNfiaboh Gaston NyahStephen Mbigha Ghogomu (Corresponding Author) - University of BueaRobert Adamu Shey (Corresponding Author) - University of Buea
- Publication Details
- bioRxiv : the preprint server for biology
- Number of pages
- 44
- Resource Type
- Preprint
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Other Identifier
- 991022238452204721