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Journal : Narra X

In silico design of a multi-epitope rabies vaccine candidate incorporating African HLA diversity: A reverse vaccinology approach Afnani, Moh R.; Emilia, Nur F.; Nurlaili, Efi; Rovik, Anwar; Ansori, Arif NM.; Parikesit, Arli A.; Chatterjee, Shrabonti; Mahata, Joydeep; Firdous, Athika; Sahadewa, Sukma; Khairullah, Aswin R.; Adnyana, I MDM.; Rebezov, Maksim; Abdurasulov, Abdugani; Durry, Fara D.; Rollando, Rollando
Narra X Vol. 4 No. 1 (2026): April 2026 (In Press)
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narrax.v4i1.263

Abstract

Rabies remains a neglected zoonotic disease with disproportionately high incidence and mortality across African regions, highlighting the need for improved and population-tailored preventive strategies. The aim of this study was to design and evaluate a multi-epitope rabies vaccine candidate targeting the rabies virus glycoprotein using a reverse vaccinology and immunoinformatics approach, with consideration of African human leukocyte antigen (HLA) allele diversity. A total of eleven cytotoxic T-lymphocyte (CTL), nine helper T-lymphocyte (HTL), and nine B-cell linear epitopes were predicted and subsequently filtered based on immunogenicity, interferon-gamma (IFN-γ) induction potential, antigenicity, allergenicity, and toxicity. The selected epitopes were assembled into a vaccine construct using appropriate adjuvants and immunostimulatory linkers. Population coverage analysis demonstrated a high theoretical coverage of 99.95% across five African subregions, underscoring the advantage of region-specific vaccine design. The final construct exhibited favorable physicochemical properties, including an instability index of 29.00 and a Grand Average of Hydropathy (GRAVY) score of -0.304, indicating stability and hydrophilicity. Structural validation showed 95.6% residues in favored regions of the Ramachandran plot, with an ERRAT score of 98.86 and a ProSA Z-score of -3.26. Molecular docking with toll-like receptor 4 (TLR4) revealed strong binding interactions, including 35 hydrogen bonds and ten salt bridges. Immune simulation predicted robust humoral and cellular responses with memory cell formation, while normal mode analysis supported structural stability and flexibility. Furthermore, the construct was successfully codon-optimized (codon adaptation index: 0.97; GC content: 51%) and in silico cloned into the pET-28a(+) vector, indicating potential for expression in Escherichia coli. These findings support the theoretical feasibility of a population-specific rabies vaccine candidate and warrant further experimental validation.
Co-Authors Aan Andriyansyir Saputra Aaqilah Hanaan Arianti Abdurasulov, Abdugani Achmad Luqmanul Hakim Adinda Ayu Noveriera Adjen Falah Muhammad Adnyana, I MDM. Aflacha Alivia Risalatul I Afnani, Moh R. Agusniar Furkani Listyani Agusniar Furkani Setiyawati Al Husnah, Syahdah Iksiroh Alya Rahmaningrum Alya Rosyidah Putri Ramadhani Ananda Rigi Aditya Andiani Andiani Andiani, Andiani Andra Agnez Al Aska Angelica, Gusti Ayu Gresia Angga Putra Surya Rahmadhani Anggaresta, Dewa Putu Kresna Ansori, Arif NM. Aqliyah, Fithratil Ardhi Wanda Arisdinata, Frederica Amelia Putri Ayu Artha Putri, Awanda Dias Rizkia Atik Sri Wulandari Atmaja, Peter Y. Aulia Putri, Desmatika Ayly Soekanto Ayu Cahyani Noviana Bayu Prakoso, Bayu Cesarea, Haning Chatterjee, Shrabonti Choiro, Anis Nurun Christin Merlina Wattimury Claudia Key Deby Rahmayanti Denik Putri Nabilasari Derkho, Marina Devi Dwi Rianti, Emilia Dharmayani, Ni Made Gita Gayatri Diana Diana Dikry Sada Amaltullah Dilla Dayana Putri Dordya Paquita Wijaya Dorta Simamora Durry , Fara Disa Durry, Fara D. Dwiari, Ni Made Mawar Edwin Edwin Efendi, Wiyoga Agung Eka Wulandari Emanuel, Endrayana Putut Laksminto Emilia Devi Dwi Rianti Emilia, Nur F. Emillia Devi D.Rianti, Emillia Devi Erny Erny Erny Erny Ethica, Stalis N. Eufemia, Eufemia Fairus Firdani Azzaky Fara Disa Durry Firdous, Athika Fuad Ama Gandhi I., I Gusti Agung Bagus GEDE ABI YOGA Gede Abi Yoga Gede Vito Chanda P Gegel Purnomo Wicaksono Gere Yusuf Kelly Giri, Made Widiantara Hanna Windyantini Hannah Izzati Hardiyono Hardiyono Hardiyono Hardiyono Hendrawan, Yucky Hendriansyah, Muhammad Hafizh Herawaty, Wike Hesty Mustika Rachmah I Komang Adhi Arya Yudanta I Made Krisna Naradha I Putu Agus Aris Wijaya Kusuma I Putu Oktayana Idwar, Herizal Ima Arum Lestarini Jamaluddin, Indra P. Jordhy Akbar KADEK DWIPA Kadek Dwipa Kadek Gede Dhiyo Bhargo Yasa Kadek Rachmawati Kadek Rio Risnanda Kadriyan, Hamsu Kartika Ishartadiati Keysha Amira Hanny Khairullah, Aswin R. Kumara Danta, I Made Kusuma, I Gusti Bagus Dharma lailatul jannah Latifunisa, Shabira Hasna Lilis Sulistyorini Lionesya Sukma Winata Listyawati, Agusniar Furkani Lusiani Tjandra M. Raffli Naresca Pradana M. Rizky Cahyo M.Raffli Naresca Pradana Mahata, Joydeep Mahayutha, I Putu Bagus Yustitio MANDASARI DWI PERTIWI Mandasari Dwi Pertiwi Maria Juliati Kusumaningtyas Masfufatun Masnuna W., Diti Nabilah Mochammad Mirza Arif Pranata Mohammad Irgi Hamdani Mukarimatussa’ada, Alva Murtadlo, Ahmad AA. Musa, Susan H. Nadilah Amanda Naw, Sin W. Ni Kadek Niken Ayu Lestari Ni Luh Komang Ayu Hertina Sintara Ni Made Shinta Putri Kesumantara Ni Putu Santhi Cahya Dewi Nike Salindri Niken Triyulianita S Niluh, Niluh Nofa, Ilham NOVA NOVITA Noveriera, Adinda Ayu Novia Restu Windayani, Novia Restu Noviana, Cahyani Nur Anggraini, Dian Eka Nur Khamidah Nurachmawati Meindah Sari Nurlaili, Efi Nurul Yaqin Nurwasilah Nurwasilah, Nurwasilah Nutdfah Nurmiftsa Palupi, Hana Indi Tisyria Cipto Parikesit, Arli A. Permatasari, Kiswati Rozi Pinatih, Januartha Putra Prada Marwah Al Kamilah Pranaya, Randy Hadyan Prasetya, Johan Danu Prasetyaning Estu Pratiwi Putri Listia, Cory Artania Putu Ayu Aryanda Parawidnyaningsih Putu Oky Ari Tania Putut Laksminto Emanuel R. Azizah Rachmawati, Anisa Nur Rahadian Zainul Rahma, Salsabila Rani Nur Rafli Amalia Rayhanah Nadzifiah Rebezov, Maksim Reisner Reza Hesty Viona Rismawaty, Ika Rollando, Rollando Rovik, Anwar Ruby Riana Asparini Safitri, Warini Ayu Salsabila, Elsa Salsabila, Puteri Sandra Miladyna Sanusi, Obed Nelson Satriyo Nugroho, Satriyo Sella Dela Hanna Putri Aziz Shita, Shita Siti Hadijah Sofyana, Nuril Maulidah Sri Lestari Utami Sri Masyeni, Dewa Ayu Putri Sucipto Sudharma, I Putu Bagus Arya Triesta Mystah Istyadzah Utami, Sri Lestari Viona Rindu Pristia Wahyuni Dyah Parmasari, Wahyuni Dyah Wijaya, Putu Listya Ayu Wike Herawaty Wike Herawaty Winata, Lionesya Sukma Yanuar Rizka Nuraida Yosephi, Valensa Yudistira, I Kadek Alam Yuniekawati, Yuyun Yusuf Badrus Zahida, Farah Zahrah Aswa Ananta Zulfan Febriawan Zulfan Febriawan Zulfi Zaskia Ramadhini