SARS-CoV-2 and its variants caused the COVID-19 pandemic. Vaccines that target conserved regions of SARS-CoV-2 and stimulate protective T-cell responses are important for reducing symptoms and limiting the infection. Seven cytotoxic (CTL) and five helper T-cells (HTL) epitopes from ORF1ab were identified using NetCTLpan and NetMHCIIpan algorithms, respectively. These epitopes were generated from ORF1ab regions that are evolutionary stable as reflected by zero Shannon’s entropy and are presented by 56 human leukocyte antigen (HLA) Class I and 22 HLA Class II, ensuring good coverage for the Indonesian and world population. Having fulfilled other criteria such as immunogenicity, IFNγ inducing ability, and non-homology to human and microbiome peptides, the epitopes were assembled into a vaccine construct (VC) together with β-defensin as adjuvant and appropriate linkers. The VC was shown to have good physicochemical characteristics and capability of inducing CTL as well as HTL responses, which stem from the engagement of the vaccine with toll-like receptor 4 (TLR4) as revealed by docking simulations. The most promiscuous peptide ⁸⁹⁹WSMATYYLF⁹⁰⁷ was shown via docking simulation to interact well with HLA-A*24:07, the most predominant allele in Indonesia. The data presented here will contribute to the in vitro study of T-cell epitope mapping and vaccine design in Indonesia.

Reports on T-cell cross-reactivity against SARS-CoV-2 epitopes in unexposed individuals have been linked with prior exposure to the human common cold coronaviruses (HCCCs). Several studies suggested that cross-reactive T-cells response to live attenuated vaccines (LAVs) such as BCG (Bacillus Calmette–Guérin), OPV (Oral Polio Vaccine), and MMR (measles, mumps, and rubella) can limit the development and severity of COVID-19. This study aims to identify potential cross-reactivity between SARS-CoV-2, HCCCs, and LAVs in the context of T-cell epitopes peptides presented by HLA (Human Leukocyte Antigen) alleles of the Indonesian population. SARS-CoV-2 derived T-cell epitopes were predicted using immunoinformatics tools and assessed for their conservancy, variability, and population coverage. Two fully conserved epitopes with 100% similarity and nine heterologous epitopes with identical T-cell receptor (TCR) contact residues were identified from the ORF1ab fragment of SARS-CoV-2 and all HCCCs. Cross-reactive epitopes from various proteins of SARS-CoV-2 and LAVs were also identified (15 epitopes from BCG, 7 epitopes from MMR, but none from OPV). A majority of the identified epitopes were observed to belong to ORF1ab, further suggesting the vital role of ORF1ab in the coronaviruses family and suggesting it as a candidate for a potential universal coronavirus vaccine that protects against severe disease by inducing cell mediated immunity.

Objective: The aim of this paper is to identify the list of microRNA (miRNA) which can regulate the aberrant expression of IQGAP in liver cancer formation. The aberrant expression of IQ motif-containing GTPase-activating protein (IQGAP) family which consists of IQGAP1, IQGAP2, and IQGAP3 has been linked to carcinogenesis in human cancers. The reciprocal expression of IQGAP family in human cancer has been studied to act as oncogenes or tumor suppressor genes. A growing number of studies suggest that upregulated or downregulated expression of IQGAP family triggers cancer development.Methods: A correlation study was performed to construct a pathway to inhibit or activate IQGAP family between miRNAs and IQGAPs. A pre-processing step was conducted to download, filter and process the dataset from TCGA. It yields miRNA and IQGAP gene expression matrix. Then, correlation computation was computed using MATLAB. Moreover, this study linked the results to the MiRTarBase to validate the prediction result with the wet lab experimental result.Results: This study identified significantly inversely correlation in 51 miRNAs-IQGAP1, 169 miRNAs-IQGAP2, and 33 miRNAs-IQGAP3, respectively, which may potentially play a role in a liver cancer formation. Some of the results also can be found in miRTarBase. It supports the precision of those miRNA and IQGAP interaction between dry lab and wet lab study. IQGAP1 and IQGAP2 mostly has been identified as an oncogene in cancer but IQGAP2 has been discovered as tumor suppressor gene. The list of miRNA in the result of this study can become a potential therapy to target the aberrant expression of IQGAP family.Conclusion: miRNA function is known as an oncogene or tumor suppressor gene in cancer development. Therefore, it can be one of the important molecular biology which may target the aberrant expression of IQGAP in liver cancer.