Immunoinformatics Analysis of Citrullinated Antigen as Potential Multi-peptide Lung Cancer Vaccine Candidates for Indonesian Population.

Non-small-cell lung cancer (NSCLC) is the most common lung cancer which has the highest mortality rate in Indonesia. One of the trends in treating cancer is by utilizing peptide vaccines, an immunotherapeutic approach that aims to stimulate the cell-mediated adaptive immune system to recognize cancer-associated peptides. Currently, no peptide vaccines are available in the market for NSCLC treatment. Therefore, this project aims to develop a multi-epitope peptide-based vaccine for NSCLC utilizing citrullinated peptides. Citrullination is a post-translational modification that occurs in cancer cells during autophagy that functions to induce immune responses towards modified self-epitopes such as tumor cells, through activation of PAD enzymes within the APC and target cells. It was found that introducing a common citrullinated neo-antigen peptide such as vimentin and enolase to the immune system could stimulate a higher specific CD4+ T cell response against NSCLC. Moreover, carcinoembryonic antigen (CEA), an antigen that is highly expressed in cancer cells, is also added to increase the vaccine's specificity and to mobilize both CD4+ and CD8+ T cells. These antigens bind strongly to the MHC Class II alleles such as HLA-DRB1*07:01 and HLA-DRB*11:01, which are predominant alleles in Indonesian populations. Through in silico approach, the peptides generated from CEA, citrullinated vimentin and enolase, were analyzed for their MHC binding strength, immunogenicity, ability to induce IFNγ response, and population coverage. It is expected that the immunodominant antigens presentation is able to induce a potent immune response in NSCLC patients in Indonesia, resulting in tumor eradication.

Immunoinformatics Identification of the Conserved and Cross-Reactive T-Cell Epitopes of SARS-CoV-2 with Human Common Cold Coronaviruses, SARS-CoV, MERS-CoV and Live Attenuated Vaccines Presented by HLA Alleles of Indonesian Population.

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.