Vaccine adjuvants: past, current and future

Adjuvants are an essential component of modern vaccines. An adjuvant is an entity added to a vaccine formulation to ensure that robust immunity to the antigen is inoculcated. The adjuvant is typically vital for the efficacy of vaccines using subunit [pepdids, proteins and virus like particles] and DNA antigens. Furthermore, these components are used to reach the current new goals of preventing and/ or treating chronic infectious diseases and cancers. This review focuses on formulation aspects of adjuvants, safety considerations, progress in understanding their mechanisms of action and also their side effects with using 97 articles are acceceble in pubmed central and google scholar indexing which published during 1980-2016. Adjuvants can be broadly divided into two classes, based on their principal mechanisms of action; the first class are vaccine delivery systems that generally particulate and mainly function to target associated antigens into antigen presenting cells. The others are immunostimulatory adjuvants that predominantly derived from pathogens and often represent pathogen associated molecular patterns which activate cells of the innate immune system. Adjuvants induce cellular and humoral responses, in particular neutralizing antibodies that able to inhibit the binding of pathogens to their cellular receptors. Efficient Th1-immunity-inducing adjuvants are highly in demand. The adjuvants promote good cell-mediated immunity against subunit vaccines that have low immunogenicity themselves. However, attempts to develop a new generation of adjuvants, which are essential for new vaccines, is important, but their use is limited because, little is known about their mechanisms of action and health risks

A review of prediction methods of interaction sites of antibody-protein complexes based on artificial intelligence

Introduction: Cancer is one of the most important health issues in the current and next centuries. Understanding the mechanism of interaction between antibody-protein residues is essential for designing targeted anticancer drugs based on monoclonal antibodies. Prediction of the effective structure is the first step for production of monoclonal antibodies

Methods: This paper is a systematic review of the state-of-the-art researches on prediction of interaction sites and specification of antibody structures. Artificial neural networks or web servers are frequently used for evaluation of interaction sites while some researchers have employed evolutionary algorithms for prediction of the effective structure of antibodies. Accordingly, 14 methods based on the protein spatial structure, 28 researches based on the molecular amino-acide sequence [without usage of the spatial structure], and 18 antigen/antibody structure prediction techniques were reviewed

Results: We demonstrated that the accuracy of structure-based methods can be increased up to 80 percent while the acuracy of sequence-based methods was rarely better than 75 percent. Since the spatial structure of many antibodies is unknown, some researchers raised the accuracy [even to 96 percent] by only antibody sequences able to interact with some similar antigens in training neural networks. Therefore, we suggest this approach for structure prediction of monoclonal antibodies because of its adequate high accuracy

Conclusion: In this paper, after reviewing available methods for prediction of antibody-protein interaction sites, some suggestions were made for effective prediction of structure of monoclonal antibodies

Viral evasion and subversion mechanisms of the host immune system

Viruses are the most abundant and versatile pathogens which challenge the immune system and cause major threats to human health. Viruses employ different mechanisms to evade host immune responses that we describe them under the following headings: Inhibition of humoral responses, Interference with interferons, Inhibition and modulation of cytokines and chemokines, Inhibitors of apoptosis, Evading CTLs and NKs, and modulating MHC function. Viruses inhibit humoral immunity in different ways which contains change of viral antigens, production of regulatory proteins of complement system and receptors of the Fc part of antibodies. Viruses block interferon production and function via interruption of cell signaling JAK/STAT pathway, Inhibition of eIF-2alpha phosphorylation and translational arrest and 2'5'OS/RNAse L system. Also, Poxviruses produce soluble versions of receptors for interferons. One of the most important ways of viral evasion is inhibition and manipulation of cytokines; for example, Herpsviruses and Poxviruses produce viral cytokines [virokines] and cytokine receptors [viroceptors]. In addition, viruses change maturation and expression of MHC I and MHC II molecules to interrupt viral antigens presentation and hide them from immune system recognition. Also, they inhibit NK cell functions. In this review, we provide an overview of the viral evasion mechanisms of immune system. Since most viruses have developed strategies for evasion of immune system, if we know these mechanisms in detail we can fight them more successfully

Down-regulation of CD14 transcripts in human glioblastoma cell line U87 MG

Pattern recognition receptors [PRRs] are the main sensors of pathogen and danger signals in innate immunity of which Toll Like Receptors [TLRs] are the most studied ones. The contribution of PRRs in cerebral inflammation induced by microbial infection, tissue damage and cancer has not extensively been addressed so far. Glioma is the most common tumor of the central nervous system and glioblastomas are the most common and most malignant primary brain tumors. The objectives of the present study were to investigate the expression of several PRRs including TLR2, TLR4, MyD88 and CD14 transcripts in human glioblastoma cell line U87 MG and compare their expression level with peripheral blood mononuclear cells [PBMC] obtained from healthy individuals. Touchdown PCR [TD-PCR] and Real-time quantitative PCR [qPCR] were applied to detect and quantify the expression level of TLR2, TLR4, MyD88 and CD14 transcript in U87 MG cell line and [PBMC] of healthy individuals. According to our results, human glioblastoma cell line U87 MG expresses TLR2, TLR4, MyD88 and CD14 transcripts in TDPCR. Moreover, the quantification of the expression of these genes revealed a highly significant down-regulation of CD14 and a slight up-regulation of TLR2 transcripts as compared to PBMC of healthy individuals. The lower expression level of CD14 in human glioblastoma cell line, might have a potential implication for CD14 mediated cerebral pathology