1545-5963 (c) 2019 IEEE. Personal use is permitted, but republication/redistribution requires IEEE permission. See http://www.ieee.org/publications_standards/publications/rights/index.html for more information. This article has been accepted for publication in a future issue of this journal, but has not been fully edited. Content may change prior to final publication. Citation information: DOI 10.1109/TCBB.2019.2958803, IEEE/ACM Transactions on Computational Biology and Bioinformatics 1 Designing a new multi-epitope pertussis vaccine with highly population coverage based on a novel sequence and structural filtration algorithm Authors: Atefeh Ghasemnejad 1 , Samira Bazmara 2 , Mahsa Shadmani 2 , Kamran Pooshang Bagheri 2* Addresses: 1. Department of Biotechnology, Faculty of Advanced Sciences & Technology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran (IAUPS) 2. Venom and Biotherapeutics Molecules Lab., Biotechnology Dept., Biotechnology Research Center, Pasteur Institute of Iran. Tehran, Iran. Corresponding author: Kamran Pooshang Bagheri Venom and Biotherapeutics Molecules Lab., Medical Biotechnology Dept., Biotechnology Research Center, Pasteur Institute of Iran. Tehran, Iran. Telefax: (+98) 21-66480780, E-mail: k_bagheri@pasteur.ac.ir Running title: Designing a new multi-epitope pertussis vaccine Abstract—Pertussis vaccine is produced from physicochemically inactivated toxin for many years. Recent advancements in immunoinformatics [1] and structural bioinformatics can provide a new multidisciplinary approach to overcome the concerns including unwanted antibodies and incomplete population coverage. In this study we focused on solving the challenging issues by designing a multi-epitope vaccine (MEV) using rational bioinformatics analyses. The frequencies of All HLA DP, DQ, and DR alleles were evaluated in almost all countries. Strong binder surface epitopes on the pertussis toxin were selected based on our novel filtration strategy. Finally, the population coverage of MEV was determined in the candidate country.. Filtration steps yielded 312 strong binder epitopes. Finally, 8 surface strong binder epitopes were selected as candidate epitopes. The population coverage of the MEV in France and the world was 98 and 100 %, respectively. Our algorithm successfully filtered many unwanted strong binder epitopes. Considering the HLA type of all individuals in a country, we theoretically provided the maximum chance to all humans to be vaccinated efficiently. Application of a MEV would be led to production of highly efficient target specific antibodies, significant reduction of unwanted antibodies, and avoid possible raising of auto-antibodies as well. Index Terms— Multi-epitope vaccine, pertussis toxin, vaccine designing, bioinformatics, HLA, population coverage, antibody 1. Introduction The vaccines have being implemented against some human infectious diseases to overcome some human health major concerns. During the past decades up to now, this strategy successfully followed to prevent the disease onset or reduction of the severity of signs or sequels. In reference to many documented reports, some critical complications may be happened after vaccination including febrile seizure and autoimmunity [2], [3]. Pertussis, Diphtheria, Tetanus, Mumps, Measles, Rubella, Hepatitis, Haemophilus influenza, and inactivated polio virus vaccines are the current vaccines that were annually injected based on the national or international schedules [4]. One of the life threatening infectious diseases of the old world is Pertussis.