Published Research Papers

Background: Malaria caused by Plasmodium vivax affects more than eight million individuals annually and remains without a licensed vaccine. PvRBP3 — a 2,797 amino-acid reticulocyte-binding invasion ligand — constitutes an essential mediator of blood-stage infection and a high-priority vaccine antigen target. Methods: We applied the Rami Five-Checkpoint Framework (R5CF) — a mathematically rigorous, systems-level in-silico pipeline — to rationally design a multi-epitope mRNA vaccine targeting PvRBP3 (GenBank: QDH08878.1). Five sequential optimization checkpoints address antigen selection, codon optimization, RNA structural validation, immunogenicity assessment, and manufacturing feasibility. Key Results: Epitope prediction identified 549 strong MHC-I binders and 102 strong MHC-II binders. Twelve MHC-I and eight MHC-II epitopes were selected (all IC50 < 85 nM). The final 1,253-nucleotide mRNA construct achieves 95.0% estimated global HLA population coverage, incorporates N1-methylpseudouridine modification, and is designed for LNP delivery using ALC-0315 or SM-102 ionizable lipid platforms. Checkpoint 5 scores C5 = 0.72, confirming manufacturing feasibility at industrial scale. Global composite score F(S) = 0.837. Significance: This document presents the first systematic application of the Rami Five-Checkpoint Framework to a blood-stage malaria antigen, providing a complete computational vaccine design with fully reproducible sequences, code, protocols, and manufacturing guidance. All findings are theoretical and require experimental validation.

Background: Coronary artery disease (CAD) represents the leading cause of mortality globally, with disproportionate burden in South Asian populations. While genome-wide association studies (GWAS) have identified 50+ CAD susceptibility loci, predominantly in European-ancestry cohorts, generalizability to other populations remains unclear. Population-specific genetic studies are essential for the equitable implementation of precision medicine. Objective: To assess the association of six well-validated CAD-associated SNPs with disease in an Indian case-control cohort, evaluate population-specific effect sizes, develop a population-optimized polygenic risk score (PRS), and examine transferability of European-derived loci. Methods: Case-control study design with 1,000 CAD cases and 1,000 controls. Genotyping of six SNPs (rs1333049, rs10757278, rs2075291, rs4977574, rs9349379, rs7173743) using targeted platforms. Logistic regression modeling with prespecified clinical covariates. Population-optimized PRS development with internal cross-validation. Expected Results: Three to four SNPs demonstrating significant association with CAD after multiple-testing correction. Population-optimized PRS with AUC 0.62-0.68 in cross-validation. Effect sizes comparable to or distinct from European estimates. Clear evidence regarding locus transferability and allele-frequency effects. Projected Impact (Planned Study): This study is designed to generate population-specific genetic evidence for CAD risk in South Asian populations, supporting precision health implementation and addressing health equity gaps in genetic research. Results are expected to clarify whether European-derived CAD loci apply universally or require population-specific calibration. Study Status: This record is a study protocol/proposal. The results described under 'Expected Results' are anticipated findings, not measured outcomes.