Novel Applications of Immuno-bioinformatics in Vaccine and Bio-product Developments at Research Institutes

Document Type: Review Article


1 Department of FMD, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran

2 Department of Avian Vaccine,Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran

3 Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran

4 Department of Genetics, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran

5 Department of Serotherapy, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran


There are many challenges in the field of public health sciences. Rational decisions are required in order to treat different diseases, gain knowledge and wealth regarding research, and produce biological or synthetic products. Various advances in the basic laboratory science, computer science, and the engineering of biological production processes can help solve the occurring problems. Bioinformatics is defined as a field of science combined of biology, mathematics, physics, chemistry, and computer sciences. Recently, bioinformatics has been extensively used in the designing of the epitope, vaccines, antibodies, adjuvants, diagnostic kits, and therapeutic purposes (e.g., proteins, peptides, or small molecules). Moreover, bioinformatics includes chemoinformatics that has been employed to produce various biological or chemical products to target and combat pathogens. Bioinformatics is involved in other areas of data analysis and prediction, such as structural biology, system biology, phylogeny, population genetics, and next-generation data sequencing. To the best of our knowledge, no published study coherently described the benefits of bioinformatics fields applied for medication development or diagnostic aims in bio-productive and pharmaceutical/vaccine companies. Therefore, in the current review, we attempted to present the available bioinformatics resources, practical experiences, and other findings in the mentioned field along with providing a harmonized and applied model(s). The key points presented in the current review may help to elevate production and reduce the costs for the development of novel vaccines, medicines, and antibodies. In addition, these methods can facilitate the identification of organisms and may guarantee the quality of biological products.


Main Subjects

Article Title [French]

Nouvelles applications de l’immuno-bioinformatique dans le développement de vaccins et de bioproduits dans les instituts de recherche

Abstract [French]

Il existe de nombreux défis dans le domaine des sciences de la santé publique. Des décisions rationnelles sont nécessaires pour traiter différentes maladies, acquérir des connaissances et une richesse en matière de recherche et produire des produits biologiques ou synthétiques. Divers progrès dans les sciences fondamentales de laboratoire, l'informatique et l'ingénierie des processus de production biologique peuvent aider à résoudre les problèmes qui se posent. La bioinformatique est définie comme un domaine scientifique d'objectifs thérapeutiques (protéines, peptides ou petites molécules, par exemple). De plus, la bioinformatique comprend la chimioinformatique qui a été utilisée pour produire divers produits biologiques ou chimiquescombinant biologie, mathématiques, physique, chimie et informatique. Récemment, la bioinformatique a été largement utilisée dans la conception d'épitopes, de vaccins, d'anticorps, d'adjuvants, de kits de diagnostic et destinés à cibler et à combattre les agents pathogènes. La bioinformatique intervient dans d'autres domaines de l'analyse et de la prévision des données, tels que la biologie structurale, la biologie des systèmes, la phylogénie, la génétique des populations et le séquençage de la prochaine génération (NGS). Au meilleur de nos connaissances, aucune étude publiée ne décrivait de manière cohérente les avantages des domaines de la bioinformatique appliqués au développement de médicaments ou d’outils de diagnostic dans les entreprises de bioproduction de vaccins et dans les sociétés pharmaceutiques. Par conséquent, dans cette revue de la litérature, nous avons tenté de présenter les ressources en bioinformatique disponibles, les expériences pratiques et d’autres résultats dans le domaine mentionné, tout en fournissant un ou plusieurs modèles harmonisés et appliqués. Les points clés présentés dans le présent rapport pourraient contribuer à augmenter la production et à réduire les coûts de développement de nouveaux vaccins, médicaments et anticorps. De plus, ces méthodes peuvent faciliter l'identification des organismes et garantir la qualité des produits biologiques.

Keywords [French]

  • Bioinformatique
  • Produits biologiques
  • Immuno-informatique
  • Vaccin
Baran, D., Pszolla, M.G., Lapidoth, G.D., Norn, C., Dym, O., Unger, T., et al., 2017. Principles for computational design of binding antibodies. Proc Natl Acad Sci USA 114, 10900-10905.

Bragazzi, N.L., Gianfredi, V., Villarini, M., Rosselli, R., Nasr, A., Hussein, A., et al., 2018. Vaccines Meet Big Data: State-of-the-Art and Future Prospects. From the Classical 3Is ("Isolate-Inactivate-Inject") Vaccinology 1.0 to Vaccinology 3.0, Vaccinomics, and Beyond: A Historical Overview. Front Public Health 6, 62.

Cafardi, V., Telford, J.L., Serruto, D., 2013. Bacterial Genomes and Vaccine Design. In: Flower, D.R., Perrie, Y. (Eds.), Immunomic Discovery of Adjuvants and Candidate Subunit Vaccines, Springer New York, New York, NY, pp. 13-37.

Cai, Z., Zhang, T., Wan, X.F., 2011. Concepts and applications for influenza antigenic cartography. Influenza Other Respir Viruses 5 Suppl 1, 204-207.

Carter, D.M., Darby, C.A., Johnson, S.K., Carlock, M.A., Kirchenbaum, G.A., Allen, J.D., et al., 2017. Elicitation of Protective Antibodies against a Broad Panel of H1N1 Viruses in Ferrets Preimmune to Historical H1N1 Influenza Viruses. J Virol 91, 24

Castiglione, F., Tieri, P., Palma, A., Jarrah, A.S., 2016. Statistical ensemble of gene regulatory networks of macrophage differentiation. BMC Bioinformatics 17, 119-128.

Christensen, D., 2016. Vaccine adjuvants: Why and how. Hum Vaccin Immunother 12, 10, 2709-2711.

Dadmanesh, M., Ranjbar, M.M., Alavian, S.M., Ghorban, K., 2015. Sequencing and Phylogenetic Study of Partial NS3 Gene of Iranian GB Virus C/Hepatitis G Virus (HGV) Originated From Hemodialysis Patients in Tehran. Hepat Mon 15, e24173.

Dimitrov, I., Flower, D.R., Doytchinova, I., 2013. AllerTOP--a server for in silico prediction of allergens. BMC Bioinformatics 14 Suppl 6, S4.

Diniz, W.J., Canduri, F., 2017. REVIEW-ARTICLE Bioinformatics: an overview and its applications. Genet Mol Res 16, 1.

Farhadi, T., Fakharian, A., Hashemian, S.M., 2017. Affinity Improvement of a Humanized Antiviral Antibody by Structure-Based Computational Design. Int J Pept Res Ther 25, 181-186.

Farhadi, T., Ovchinnikov, R.S., Ranjbar, M.M., 2016. In silico designing of some agonists of toll-like receptor 5 as a novel vaccine adjuvant candidates. Netw Model Anal Health Inform Bioinform 5, 31.

Fernald, G.H., Capriotti, E., Daneshjou, R., Karczewski, K.J., Altman, R.B., 2011. Bioinformatics challenges for personalized medicine. Bioinformatics 27, 1741-1748.

Fong, L.E., Munoz-Rojas, A.R., Miller-Jensen, K., 2018. Advancing systems immunology through data-driven statistical analysis. Curr Opin Biotechnol 52, 109-115.

Giles, B.M., Ross, T.M., 2011. A computationally optimized broadly reactive antigen (COBRA) based H5N1 VLP vaccine elicits broadly reactive antibodies in mice and ferrets. Vaccine 29, 3043-3054.

Hegde, N.R., Gauthami, S., Sampath Kumar, H.M., Bayry, J., 2018. The use of databases, data mining and immunoinformatics in vaccinology: where are we? Expert Opin Drug Discov 13, 117-130.

Keyvani, H., Ahmadi, N.A., Ranjbar, M.M., Ataei Kachooei, S., Ghorban, K., Dadmanesh, M., 2016. Immunoinformatics Study of gp120 of Human Immunodeficiency Virus Type 1 Subtype CRF35_AD Isolated from Iranian Patients. Arch Clin Infect Dis 11, 4, e36270.

Koellhoffer, J.F., Higgins, C.D., Lai, J.R., 2014. Protein engineering strategies for the development of viral vaccines and immunotherapeutics. FEBS Lett 588, 298-307.

Krammer, F., 2017. Strategies to induce broadly protective antibody responses to viral glycoproteins. Expert Rev Vaccines 16, 503-513.

Leelananda, S.P., Lindert, S., 2016. Computational methods in drug discovery. Beilstein J Org Chem 12, 2694-2718.

Luciani, F., 2016. High-throughput sequencing and vaccine design. Rev Sci Tech 35, 53-65.

Malekan, M., VasfiMarandi, M., Barin, a., Mokhtari azad, T., Ranjbar, M.M., Bashashati, M., 2016. Molecular evaluation of M2 protein of Iranian avian influenza viruses of H9N2 subtype in order to find mutations of adamantane drug resistance. Iranian J Vet Med 10, 253-262.

McGarvey, P.B., Suzek, B.E., Baraniuk, J.N., Rao, S., Conkright, B., Lababidi, S., et al., 2014. In silico analysis of autoimmune diseases and genetic relationships to vaccination against infectious diseases. BMC Immunol 15, 61.

Nakaya, H.I., Clutterbuck, E., Kazmin, D., Wang, L., Cortese, M., Bosinger, S.E., et al., 2016. Systems biology of immunity to MF59-adjuvanted versus nonadjuvanted trivalent seasonal influenza vaccines in early childhood. Proc Natl Acad Sci USA 113, 1853-1858.

Nikbin, B., Nicknam, M.H., Hadinedoushan, H., Ansaripour, B., Moradi, B., Yekaninejad, M., et al., 2017. Human leukocyte antigen (HLA) class I and II polymorphism in Iranian healthy population from Yazd Province. Iran J Allergy Asthma Immunol 16, 1-13.

Overby, C.L., Tarczy-Hornoch, P., 2013. Personalized medicine: challenges and opportunities for translational bioinformatics. Per Med 10, 453-462.

Paricharak, S., Mendez-Lucio, O., Chavan Ravindranath, A., Bender, A., I. Jzerman A.P., van Westen, G.J.P., 2018. Data-driven approaches used for compound library design, hit triage and bioactivity modeling in high-throughput screening. Brief Bioinform 19, 277-285.

Ranjbar, M.M., Ahmadi, N.A., Ghorban, K., Ghalyanchilangeroudi, A., Dadmanesh, M., Amini, H.-R., 2015b. Immnoinformatics: Novel view in understanding of immune system function, databases and prediction of immunogenic epitopes. Koomesh 17, 18-26.

Ranjbar, M.M., Assadolahi, V., Yazdani, M., Nikaein, D., Rashidieh, B., 2016b. Virtual Dual inhibition of COX-2 / 5-LOX enzymes based on binding properties of alpha-amyrins, the anti-inflammatory compound as a promising anti-cancer drug. EXCLI J 15, 238-245.

Ranjbar, M.M., Brujeni, G.N., Mashhadi, A.G., Dabbaghyan, M., 2016a. Study of BuLA-DRB3 polymorphism in Khuzestan river buffaloes. J Vet Res 71, 33-40.

Ranjbar, M.M., Ghorban, K., Alavian, S.M., Keyvani, H., Dadmanesh, M., Roayaei Ardakany, A., et al., 2013. GB Virus C/Hepatitis G Virus Envelope Glycoprotein E2: Computational Molecular Features and Immunoinformatics Study. Hepat Mon 13, e15342.

Ranjbar, M.M., Gupta, S.K., Ghorban, K., Nabian, S., Sazmand, A., Taheri, M., et al., 2015a. Designing and modeling of complex DNA vaccine based on tropomyosin protein of Boophilus genus tick. Appl Biochem Biotechnol 175, 323-339.

Rappuoli, R., Aderem, A., 2011. A 2020 vision for vaccines against HIV, tuberculosis and malaria. Nature 473, 463-469.

Rashidieh, B., Valizadeh, M., Assadollahi, V., Ranjbar, M.M., 2015. Molecular dynamics simulation on the low sensitivity of mutants of NEDD-8 activating enzyme for MLN4924 inhibitor as a cancer drug. Am J Cancer Res 5, 3400-3406.

Shahsavandi, S., Ebrahimi, M.M., Sadeghi, K., Mahravani, H., 2015. Design of a heterosubtypic epitope-based peptide vaccine fused with hemokinin-1 against influenza viruses. Virol Sin 30, 200-207.

Sollner, J., Heinzel, A., Summer, G., Fechete, R., Stipkovits, L., Szathmary, S., et al., 2010. Concept and application of a computational vaccinology workflow. Immunome Res 6 Suppl 2, S7.

Somvanshi, P.R., Venkatesh, K.V., 2014. A conceptual review on systems biology in health and diseases: from biological networks to modern therapeutics. Syst Synth Biol 8, 99-116.

Srivastava, P., Tiwari, A., 2017. Critical Role of Computer Simulations in Drug Discovery and Development. Curr Top Med Chem 17, 2422-2432.

Suresh, R., Mosser, D.M., 2013. Pattern recognition receptors in innate immunity, host defense, and immunopathology. Adv Physiol Educ 37, 284-291.

Tiller, K.E., Chowdhury, R., Li, T., Ludwig, S.D., Sen, S., Maranas, C.D., et al., 2017. Facile Affinity Maturation of Antibody Variable Domains Using Natural Diversity Mutagenesis. Front Immunol 8, 986.

Toussi, D.N., Massari, P., 2014. Immune Adjuvant Effect of Molecularly-defined Toll-Like Receptor Ligands. Vaccines (Basel) 2, 323-353.

Usha, T., Shanmugarajan, D., Goyal, A.K., Kumar, C.S., Middha, S.K., 2017. Recent Updates on Computer-aided Drug Discovery: Time for a Paradigm Shift. Curr Top Med Chem 17, 3296-3307.

Vivcharuk, V., Baardsnes, J., Deprez, C., Sulea, T., Jaramillo, M., Corbeil, C.R., et al., 2017. Assisted Design of Antibody and Protein Therapeutics (ADAPT). PLoS One 12, e0181490.

Wiley, S.R., Raman, V.S., 2017. Molecular Methods and Bioinformatic Tools for Adjuvant Characterization by High-Throughput Sequencing. Methods Mol Biol 1494, 353-368.

Wong, T.M., Allen, J.D., Bebin-Blackwell, A.-G., Carter, D.M., Alefantis, T., DiNapoli, J., et al., 2017a. COBRA HA elicits hemagglutination-inhibition antibodies against a panel of H3N2 influenza virus co-circulating variants. J Virol, JVI, 91, 01581-01517.

Wong, T.M., Allen, J.D., Bebin-Blackwell, A.-G., Carter, D.M., Alefantis, T., DiNapoli, J., et al., 2017b. Computationally Optimized Broadly Reactive Hemagglutinin Elicits Hemagglutination Inhibition Antibodies against a Panel of H3N2 Influenza Virus Cocirculating Variants. J Virol 91, 01581-01517.