Indian Journal of Biotechnology Vol 9, October 2010, pp 351-359 Bioinformatics approach for screening and modeling of putative T cell epitopes from Por B protein of Neisseria meningitides as vaccine constructs Kavita Shah * , Priyanka Chaubey and Namrata Mishra * Bioinformatics Division, MMV, Banaras Hindu University, Varanasi 221 005, India Received 14 July 2009; revised 8 January 2010; accepted 15 March 2010 Vaccine design based on conventional approaches requires longer time for identifying candidate antigens as targets. No effective vaccine for meningitis is known, which covers all age groups. The present study is a computational approach for identification of candidate T cell epitopes from Por B protein of Neisseria meningitidis (MC58) using immunoinformatics tools and structural simulation. We report two nonameric epitopes ( 273 KGLVDDADI 282 , loop VII) and ( 170 GRHNSESYH 179 , loop IV) which exhibit good binding with MHC molecules and low energy minimization values providing stability to the peptide-MHC complex. The predicted peptides are present on the surface exposed immunogenic loops of class 3 OMP allele of Neisseria with no similarity to human proteome. These peptides could be used in designing a DNA/subunit vaccine, however, these will further be tested by wet lab studies for a targeted vaccine design against N. meningitidis strain MC58. Keywords: Conformation; meningitis; Neisseria meningitides, structural simulation; T cell epitopes Introduction With the ever increasing number of protein databases, the immunologists are using computational tools to predict which snippets of a protein, out of hundreds or thousands of possible candidates, are most likely to spark a strong immune response 1 . With more and more improvements in the tools, it may soon be feasible to skip over many of the in vitro screening steps 2 . Epitope based vaccines provide a new strategy for the prophylactic and therapeutic application of pathogen specific immunity. A critical requirement of this strategy is the identification and selection of T cell epitopes important for cytolytic and regulatory response to pathogens 3 as an aid in vaccine development 4-6 . The universal selection of protein antigen sequences that function as T cell epitopes in vaccine formulation is therefore crucial for successful application of the vaccination strategy 7-8 used for vaccine design. Early clinical trials of epitope based vaccines for human immunodeficiency virus 9 , malaria and tuberculosis 10 have produced promising results and thus supporting the identification and selection of T cell epitopes as vaccine targets 5 . Neisseria meningitidis causes meningitis and sepsis in adults. A disproportionately large number of cases among infants accounting for about 1/3 of all meningococcal invasive diseases reported from the western world 11 . There are five pathogenic N. meningitidis serogroups (A, B, C, Y & W135) as determined by capsular polysaccharide typing. The pattern of serogroup B disease is typically hyper endemic or sporadic and contrasts with the classically epidemic nature of the serogroup A 12 . The progression of disease is very rapid with clinical features as shock, subcutaneous and gingival hemorrhage, thrombosis of vessels to extremities, delirium and coma leading to death within 24 h 11 . T cell immunity is implicated in rapid clearance of a disease 13 . Therefore, a vaccine generating robust T cell immunity against N. meningitidis is of importance. Polysaccharide vaccines for meningitis have been available for almost 40 years, yet they are poorly immunogenic in young children who are at the highest risk 11,14 . So far only the polysaccharide-protein conjugate vaccines for the prevention of serogroup C meningococcal infection have proven efficacious 14 . However, to our knowledge the development of a universally safe, immunogenic and effective serogroup B Neisseria meningitidis vaccine still remains a challenge for scientists. Efforts are being made to study and characterize the epitopes from membranes and extra- cellular factors including outer membrane proteins (OMP) such as class 1 (Por A, a cation specific porin), class 2 or 3 (Por B, an anion specific protein) ________________ *Author for correspondence: Tel: 91-542-2311024; Fax: 91-542-2317074 E-mail: kavitashah@bhu.ac.in