Identification and biophysical characterization of Plasmodium peptide binding by common African HLAs

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 12, 2025

Human Leukocyte Antigens (HLA) are immunoreceptors that present peptide antigens at the cell surface to T cells as a primary mechanism of immune surveillance. Malaria, disease associated with Plasmodium parasite, claims > 600,000 lives per year globally most deaths occurring in Africa. Development efficacious prophylactic vaccines or therapeutic treatments for malaria has been hindered by lack basic understanding role HLA-mediated antigen presentation during infection. In particular, there is (i) little which presented HLAs context malaria, and (ii) structural insights into HLAs, underpins peptide/HLA stability, specificity, cross-presentation across HLA alleles, recognition receptors. To begin address these knowledge gaps, we identify characterize candidate derived from falciparum potential common class I alleles. We computationally screen nine proteins P. proteome predict eight peptides alleles African populations, HLA-A*02:01 HLA-B*08:01. then validate predictions producing recombinant complex identified vitro refolding. evaluate folding thermal stability resulting sixteen complexes CD spectroscopy nanoDSF. silico modeling informs plausible basis mechanisms HLA-B*08:01 Finally, expand our cover broader range endemic populations experimental validation provided HLA-C*07:01 HLA-E*01:03. Together, results step forward towards deeper multi-allele malaria. These further inform future development multivalent vaccine strategies targeting profiles populations.

Language: Английский

Enhancing malaria elimination in high-transmission settings: the synergy of concurrent vector control and chemotherapy

Malaria Journal, Journal Year: 2025, Volume and Issue: 24(1)

Published: April 1, 2025

Malaria elimination, defined as interrupting local transmission and reducing cases to zero, is a critical public health goal. While dual parasite-vector approach essential, the path elimination complex marked by both progress setbacks. Despite renewed commitment initiatives like "High Burden High Impact" approach, challenges persist, particularly in sub-Saharan Africa. These include shifting epidemiological profiles, weak systems, drug insecticide resistance, emerging global issues. Effective therefore, requires multi-pronged scaling-up package of interventions tailored intensity, including prompt treatment with ACT, IPTp for pregnant women, vector control measures IRS LLINs, robust community engagement. Ultimately, combination contextually appropriate strategies, implemented synergistically, will be crucial breaking cycle achieving sustained malaria elimination. This report aims review available evidence on strategies deployment current tools targeting vectors parasites resource-limited settings, focusing Combining can create synergistic effect, where combined impact greater than sum individual interventions. For example, simulations show benefits from combining MDA IRS, vaccines bed nets, or RTS,S vaccine perennial chemotherapy. However, effects are not always guaranteed; some combinations, LLINs may provide additional benefit. Conversely, MDA, SMC seasonal vaccination, has demonstrated increased protective effects. Therefore, successful efforts depend country-specific factors burden, political commitment, system capacity. significant biological operational remain, which necessitate approaches achieve Synergistic intervention crucial, but implementation context paramount. highly effective, all combinations yield equal results. Thus, tailoring specific dynamics essential maximizing impact. Moreover, heavily reliant systems understanding challenges. Consequently, adaptable, evidence-based required overcome these obstacles lasting toward

Language: Английский