The use of vaccines have resulted in a remarkable improvement in global health. It has saved several lives, reduced treatment costs and raised the quality of animal and human lives. Current traditional vaccines came empirically with either vague or completely no knowledge of how they modulate our immune system. Even at the face of potential vaccine design advance, immune-related concerns (as seen with specific vulnerable populations, cases of emerging/reemerging infectious disease, pathogens with complex lifecycle and antigenic variability, need for personalized vaccinations, and concerns for vaccines' immunological safety -specifically vaccine likelihood to trigger non-antigen-specific responses that may cause autoimmunity and vaccine allergy) are being raised. And these concerns have driven immunologists toward research for a better approach to vaccine design that will consider these challenges. Currently, immunoinformatics has paved the way for a better understanding of some infectious disease pathogenesis, diagnosis, immune system response and computational vaccinology. The importance of this immunoinformatics in the study of infectious diseases is diverse in terms of computational approaches used, but is united by common qualities related to host-pathogen relationship. Bioinformatics methods are also used to assign functions to uncharacterized genes which can be targeted as a candidate in vaccine design and can be a better approach toward the inclusion of women that are pregnant into vaccine trials and programs. The essence of this review is to give insight into the need to focus on novel computational, experimental and computation-driven experimental approaches for studying of host-pathogen interactions and thus making a case for its use in vaccine development.

Human P450 2C19 is selective for 4-hydroxylation of S-mephenytoin and 5-hydroxylation of omeprazole, while the structurally homologous P450 2C9 has low activity toward these substrates. To identify the critical amino acids that determine the specificity of human P450 2C19, we constructed chimeras of P450 2C9 replacing various proposed substrate binding sites (SRS) with those of P450 2C19 and then replaced individual residues of P450 2C9 by site-directed mutagenesis. The 339 NH 2 -terminal amino acid residues (SRS-1-SRS-4) and amino acids 160 -383 (SRS-2-SRS-5) of P450 2C19 conferred omeprazole 5-hydroxylase activity to P450 2C9. In contrast, the COOH terminus of P450 2C19 (residues 340 -490 including SRS-5 and SRS-6), residues 228 -339 (SRS-3 and SRS-4) and residues 292-383 (part of SRS-4 and SRS-5) conferred only modest increases in activity. A single mutation Ile 99 3 His increased omeprazole 5-hydroxylase to ϳ51% of that of P450 2C19. A chimera spanning residues 160 -227 of P450 2C19 also exhibited omeprazole 5-hydroxylase activity which was dramatically enhanced by the mutation Ile 99 3 His. A combination of two mutations, Ile 99 3 His and Ser 200 3 Pro, converted P450 2C9 to an enzyme with a turnover number for omeprazole 5-hydroxylation, which resembled that of P450 2C19. Mutation of Pro 221 3 Thr enhanced this activity. Residue 99 is within SRS-1, but amino acids 220 and 221 are in the F-G loop and outside any known SRS. Mutation of these three amino acids did not confer significant S-mephenytoin 4-hydroxylase activity to P450 2C9, although chimeras containing SRS-1-SRS-4 and SRS-2-SRS-5 of P450 2C19 exhibited activity toward this substrate. Our results thus indicate that amino acids 99, 220, and 221 are key residues that determine the specificity of P450 2C19 for omeprazole. The P4501 cytochromes represent a ubiquitous superfamily of monooxygenases, which metabolize a vast array of endogenous and exogenous substrates (1-3). Multiple P450 enzymes appear to have arisen from a single ancestral gene by duplication and diverged by mutation and gene conversion to produce families of structurally related enzymes with overlapping but often distinct substrate specificities. The regio-and stereoselectivity of specific enzymes for particular substrates appears to be encoded in certain defined regions of the primary sequence. Considerable progress has been made in recent years in elucidating the structural determinants of substrate specificity (4). In some cases, substrate specificity between highly related members of the same subfamily has been shown to be defined by a few critical residues or even a single amino acid (5).P450 2C19 is a member of the human CYP2C subfamily, which includes four structurally related enzymes (6). P450 2C9 and 2C19 are the most highly conserved of these forms, showing 91% structural identity, but have very distinctive substrate specificities. For example P450 2C19, which is polymorphic in man, is the principal enzyme responsible for the stereoselective 4Ј-hydroxylation of S-mephenytoin ...

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