A systematic bioinformatics approach for selection of epitope-based vaccine targets

Abstract

Epitope-based vaccines provide a new strategy for prophylactic and therapeutic application of pathogen-specific immunity. A critical requirement of this strategy is the identification and selection of T-cell epitopes that act as vaccine targets. This study describes current methodologies for the selection process, with dengue virus as a model system. A combination of publicly available bioinformatics algorithms and computational tools are used to screen and select antigen sequences as potential T-cell epitopes of supertype HLA alleles. The selected sequences are tested for biological function by their activation of T-cells of HLA transgenic mice and of pathogen infected subjects. This approach provides an experimental basis for the design of pathogen specific, T-cell epitopebased vaccines that are targeted to majority of the genetic variants of the pathogen, and are effective for a broad range of differences in human leukocyte antigens among the global human population.

Characterization ofPlasmodium falciparumProteome at Asexual Blood Stages for Screening of Effective Vaccine Candidates: An Immunoinformatics Approach

“…40 Therefore, prediction analysis of the CD8+ and CD4+ T-cell epitopes of asexual blood-stage antigens may prove to be essential in the design of a vaccine that targets the erythrocytic stage of the malaria parasite because antibodies cannot be efficiently induced in the absence of CD4+ T-cells, which play a key role in B-cell expansion, differentiation, class switching, and affinity maturation of the responses. 11 T-cell epitopes analysis of asexual blood-stage proteins. Recent approach to identify targets of CD8+ and CD4+ T-cell responses in an antigen is based on the prediction of high-affinity binding class I or class II restricted T-cell epitopes using computational algorithms.…”

“…Hence, with the above criteria, the consensually predicted 16 immunogenic antigens (nos. 1,3,5,6,7,9,11,13,15,16,19,20,22,25,26,31) using NetCTL and MULTIPRED2 could be considered as good vaccine targets for malaria and may be effective for larger human populations.…”

Integrative immunoinformatics for Mycobacterial diseases in R platform

“…Analysis of enhanced RV data through decision trees provided a list of 233 non-redundant set of most probable vaccine candidates from 23 strains and species of Mycobacteria. Recent trends of vaccinologists aim for epitope based vaccines (Patronov and Doytchinova 2013;Khan et al 2007). Towards facilitating these efforts, we analyzed the information on epitopes in terms of their conservation among orthologs (Khan et al 2007).…”

“…Recent trends of vaccinologists aim for epitope based vaccines (Patronov and Doytchinova 2013;Khan et al 2007). Towards facilitating these efforts, we analyzed the information on epitopes in terms of their conservation among orthologs (Khan et al 2007). The epitope conservation data for epitopes and its associated information including other molecular features of the protein provides facility for enablement of epitope based vaccine design.…”

CD4+ T Cell Epitope Discovery and Rational Vaccine Design

“…The alignment of peptides binding to several distinct HLA-DR molecules with TEPITOPE or other quantitative matrix MHC class II prediction algorithm can identify such potentially ''promiscuous'' epitopes. Since many pathogens exhibit high mutation rates, it is important to select conserved protein sequences for scanning with MHC-binding algorithms (Khan et al 2006).…”