Immunogenicity of NS4b dengue 3 virus mimotope presented to the immune system as multiple antigen peptide system

The availability of random peptide libraries displayed on bacteriophage (RPL) has provided a powerful tool for selecting sequences that mimic binding properties of natural antigen epitopes (mimotopes). These mimotopes can be used for vaccine design, drug development, and diagnostic assays. Several mimotopes have been shown to induce production of antibodies against the natural antigen. We have previously identified four dengue virus mimotopes from a phage-displayed peptide library using antidengue 3 human sera. Three of them showed similarity in their amino acid sequences with the NS4b proteins of dengue. Few studies have examined the role of NS4b proteins in the antibody response to dengue virus infection. A multiple antigen peptide (MAP) system was chemically synthesized containing this mimotope (NS4b MAP), and BALB/c mice were immunized to evaluate its immunogenicity. Antipeptide responses were induced and recognised DENV-3 infected cells as determined by immunofluorescence. The high levels of the IgG2a subtype against NS4bMAP suggest the induction of a Th1-like response. Our findings suggest that the NS4b mimotope might be a useful tool for the development of multiepitope diagnostic assays, dengue virus vaccine design, and pathogenesis studies

DNA vaccines: designing strategies against parasitic infections

The complexity of parasitic infections requires novel approaches to vaccine design. The versatility of DNA vaccination provides new perspectives. This review discusses the use of prime-boost immunizations, genetic adjuvants, multivalent vaccines and codon optimization for optimal DNA vaccine design against parasites

Defining T Cell Tissue Residency in Humans: Implications for HIV Pathogenesis and Vaccine Design.

Purpose of review:This review summarizes recent literature defining tissue-resident memory T cells (TRM) and discusses implications for HIV pathogenesis, vaccines, and eradication efforts.Recent findings:Investigations using animal models and human tissues have identified a TRM transcriptional profile and elucidated signals within the tissue microenvironment leading to TRM development and maintenance. TRM are major contributors to host response in infectious diseases and cancer; in addition, TRM contribute to pathogenic inflammation in a variety of settings. Although TRM are daunting to study in HIV infection, recent work has helped define their molecular signatures and effector functions and tested strategies for their mobilization. Exclusive reliance on blood sampling to gain an understanding of host immunity overlooks the contribution of TRM, which differ in significant ways from their counterparts in circulation. It is hoped that greater understanding of these cells will lead to novel approaches to prevent and/or eradicate HIV infection

CD8+ T-cell responses in vaccination: Reconsidering targets and function in the context of chronic antigen stimulation

Cytotoxic CD8 T cells play important roles in eliminating infected and transformed cells. Owing to their potential for therapeutic applications, significant efforts are dedicated toward developing CD8 T cell-based vaccines. Thus far, CD8 T-cell vaccination strategies have had limited success therapeutically in contrast to those targeting antibody-based immunity. However, if the current challenges and gaps in the understanding of T-cell biology are overcome, the full potential of rational CD8 T-cell vaccine design might be realized. Here, we review recent progress in this direction, focusing on target selection and maintenance of function in the settings of chronic infections and cancers