We used a quantitative proteomics pipeline to systematically investigate plasma host and parasite proteome alterations in falciparum and vivax malaria patients. Proteomic analysis of human plasma and parasite lysates from P. vivax patients identified five parasite proteins—PVX_090265, PVX_083555, PVX_094303, PVX_003545, and PVX_101520—expressed in human plasma and the parasite proteome. Bioinformatics analysis confirmed these candidates as specific for P. vivax. Further validation through targeted proteomics (multiple reaction monitoring; MRM) suggested their potential as biomarkers for next-generation rapid diagnostic kits for P. vivax infection. Comprehensive proteomics analysis of severe falciparum malaria revealed significant modulations in critical physiological pathways, including lipid metabolism, cytokine signaling, complement cascades, platelet degranulation, and coagulation cascades. Key blood markers—Leucine-rich glycoprotein, Ceruloplasmin, Histidine-rich glycoprotein, Zinc-alpha-2 glycoprotein, Alpha-2HS glycoprotein, and Alpha-1 antichymotrypsin—were identified as effective in defining different complications of severe falciparum malaria, such as cerebral syndromes and severe anemia. These findings could lead to the development of clinical tests for monitoring malaria severity and understanding its pathobiology.
For COVID-19, we used FTIR and high-resolution MS-based proteomics on swab and plasma samples from over 200 patients, identifying host peptides that correlated with viral load, indicating their potential as prognostic biomarkers. We further employed SARS-CoV-2 Proteome microarray, containing ~5000 peptides representing the viral proteome and mutant peptides, to study IgA and IgG responses in COVID-19 patients. Data analysis identified 204 and 676 peptides for IgA and IgG, respectively, with 6 and 443 peptides showing discriminatory potential based on disease severity. Notably, we discovered 5 (IgA) and 10 (IgG) peptides with mutations from B1.1.7, 501.V2, and P.1 eliciting immunogenic responses, particularly an increased response against the N501Y mutation in Spike and decreased response against K417T and D138Y mutations. These findings present novel IgA and IgG epitopes with disease severity discriminatory potential and altered immune responses against mutant viral epitopes. We are currently developing assays for clinical translation of these findings, aiming for efficient diagnosis and elimination of malaria, as well as improved prognosis for COVID-19.