Peptide-Based Vaccinology: Experimental and Computational Approaches to Target Hypervariable Viruses through the Fine Characterization of Protective Epitopes Recognized by Monoclonal Antibodies and the Identification of T-Cell-Activating Peptides

Abstract

Defining immunogenic domains of viral proteins capable of eliciting a protective immune response is crucial in the development of novel epitope-based prophylactic strategies. This is particularly important for the selective targeting of conserved regions shared among hypervariable viruses. Studying postinfection and postimmunization sera, as well as cloning and characterization of monoclonal antibodies (mAbs), still represents the best approach to identify protective epitopes. In particular, a protective mAb directed against conserved regions can play a key role in immunogen design and in human therapy as well. Experimental approaches aiming to characterize protective mAb epitopes or to identify T-cell-activating peptides are often burdened by technical limitations and can require long time to be correctly addressed. Thus, in the last decade many epitope predictive algorithms have been developed. These algorithms are continually evolving, and their use to address the empirical research is widely increasing. Here, we review several strategies based on experimental techniques alone or addressed by in silico analysis that are frequently used to predict immunogens to be included in novel epitope-based vaccine approaches. We will list the main strategies aiming to design a new vaccine preparation conferring the protection of a neutralizing mAb combined with an effective cell-mediated response.

Comparison of experimental fine‐mapping to in silico prediction results of HIV‐1 epitopes reveals ongoing need for mapping experiments

“…Overlapping synthetic peptides corresponding to the HIV proteins Gag, Pol and Nef were used for screening (15)(16)(17)(18)(19)(20) amino acids long, overlap of 5-10 amino acids; Gag: HIV-1 SF-2, Nef: HIV-1 Bru, NIBSC, England; Pol clade B consensus sequence of 2001 or according to patients' autologous viral sequence: EZBiolab, Carmel, IN). Truncations of longer peptides for epitope mapping were ordered as needed (EZBiolab).…”

“…Therefore, it is often replaced by bioinformatic tools. [6][7][8][9][10] A variety of computational algorithmsmany of which are freely available onlinehave been created to predict which peptides contained in a pathogen are likely T-cell epitopes [11][12][13][14][15] (reviewed in refs 16,17). We hypothesized that freely available prediction tools do not reliably predict the actually mapped CD8 T-cell epitope in all cases.…”

SplitCore Technology Allows Efficient Production of Virus-Like Particles Presenting a Receptor-Contacting Epitope of Human IgE

“…B-cell epitope-based vaccine is a concept involving artificial antigen which comprises one or more precisely defined antigenic determinants or epitopes taken out from the natural antigen and embedded into a suitable carrier [1][2][3]. The epitope-based vaccines have an important advantage, which is the ability to elicit immune response against a precisely defined antigenic determinant.…”

Adding Functions to Biomaterial Surfaces through Protein Incorporation

“…B-and T-cell immunostimulatory molecules [247] -though surprisingly, no epitope-based vaccines have yet been adopted in clinical practice, [248] as well as anti-inflammatory agents, [249] anti-cancer drugs, [250] and cell-penetrating peptides [251] with both cytotoxic and drug delivery potential. [252] Once identified, synthesis of peptides typically occurs using a recombinant (biological) production platform or a chemical synthesis approach.…”