New Immunoinformatics Tools for Swine: Designing Epitope-Driven Vaccines, Predicting Vaccine Efficacy, and Making Vaccines on Demand

Abstract

Novel computational tools for swine vaccine development can expand the range of immunization approaches available to prevent economically devastating swine diseases and spillover events between pigs and humans. PigMatrix and EpiCC are two new tools for swine T cell epitope identification and vaccine efficacy analysis that have been integrated into an existing computational vaccine design platform named iVAX. The iVAX platform is already in use for the development of human vaccines, thus integration of these tools into iVAX improves and expands the utility of the platform overall by making previously validated immunoinformatics tools, developed for humans, available for use in the design and analysis of swine vaccines. PigMatrix predicts T cell epitopes for a broad array of class I and class II swine leukocyte antigen (SLA) using matrices that enable the scoring of sequences for likelihood of binding to SLA. PigMatrix facilitates the prospective selection of T cell epitopes from the sequences of swine pathogens for vaccines and permits the comparison of those predicted epitopes with “self” (the swine proteome) and with sequences from other strains. Use of PigMatrix with additional tools in the iVAX toolkit also enables the computational design of vaccines in silico , for testing in vivo . EpiCC uses PigMatrix to analyze existing or proposed vaccines for their potential to protect, based on a comparison between T cell epitopes in the vaccine and circulating strains of the same pathogen. Performing an analysis of T cell epitope relatedness analysis using EpiCC may facilitate vaccine selection when a novel strain emerges in a herd and also permits analysis of evolutionary drift as a means of immune escape. This review of novel computational immunology tools for swine describes the application of PigMatrix and EpiCC in case studies, such as the design of cross-conserved T cell epitopes for swine influenza vaccine or for African Swine Fever. We also describe the application of EpiCC for determination of the best vaccine strains to use against circulating viral variants of swine influenza, swine rotavirus, and porcine circovirus type 2. The availability of these computational tools accelerates infectious disease research for swine and enable swine vaccine developers to strategically advance their vaccines to market.

Occurrence of Rotavirus A Genotypes and Other Enteric Pathogens in Diarrheic Suckling Piglets from Spanish Swine Farms

“…This vaccine, which is increasingly used in Spanish pig farms, consists of porcine RVA strains Gottfried (G4P6), OSU (G5P7) and A2 (G9P7) which have been modified a long time ago [12]. Moise et al [59] used computational tools to analyze the potential efficacy of this vaccine and demonstrated that T cell epitope cross-conservation between the vaccine and RVA porcine strains circulating in the United States is genotype-specific and limited to homologous strains. However, more than 200,000 sows are vaccinated every year in Spain with this vaccine (personal communication of R. Menjon) and no pharmacovigilance events suggesting a possible lack of efficacy have been reported to the Spanish Agency of Medicines and Medical Devices (available at https:// www.aemps.gob.es/acciones-informativas-medicamentos-veterinarios/?cat=291, accessed on 18 January 2022).…”

Identification of Promiscuous African Swine Fever Virus T-Cell Determinants Using a Multiple Technical Approach

“…Due to the concerns that we had when performing the in silico predictions based on a single prediction tool, we decided to perform a multiparametric analysis not only based on NetMHCpan. Despite novel immunoinformatics tools have been recently developed [ 58 ], at the time of the analysis little data was available from swine [ 59 , 60 , 61 , 62 ], which forced to complete our multiparametric prediction tool with experimental data obtained mainly from human and mouse studies. Most probably due to the imperfections of our predictive methodology, our approach has allowed the identification of only one promiscuously recognized ASFV T-cell determinant within the Georgia2007/1 MGF100-1L protein.…”

mRNA Vaccine Development for Emerging Animal and Zoonotic Diseases

“…Recently, highly conserved cytotoxic T-cell epitopes have been identified in ASFV encoded proteins through a computational vaccine design platform named iVAX [113,114]. A Tcell-directed ASF DNA vaccine containing the predicted swine MHC class I and class II epitopes was then developed, and the immunogenicity of this novel vaccine is being assessed [115][116][117]. Given the potential risk of integration into the host genome associated with DNA vaccines, the mRNA-based vaccine approach has the potential to lead to improvements for safe and effective ASF vaccines for marketing.…”