Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Background: A highly effective vaccine for malaria remains an elusive target, at least in part due to the under-appreciated natural parasite variation. This study aimed to investigate genetic and structural variation, and immune selection of leading malaria vaccine candidates across the Plasmodium falciparum's life cycle.
Methods: We analysed 325 P. falciparum whole genome sequences from Zambia, in addition to 791 genomes from five other African countries available in the MalariaGEN Pf3k Database. Ten vaccine antigens spanning three life-history stages were examined for genetic and structural variations, using population genetics measures, haplotype network analysis, and 3D structure selection analysis.
Findings: Among the ten antigens analysed, only three in the transmission-blocking vaccine category display P. falciparum 3D7 as the dominant haplotype. The antigens AMA1, CSP, MSP1 and CelTOS, are much more diverse than the other antigens, and their epitope regions are under moderate to strong balancing selection. In contrast, Rh5, a blood stage antigen, displays low diversity yet slightly stronger immune selection in the merozoite-blocking epitope region. Except for CelTOS, the transmission-blocking antigens Pfs25, Pfs48/45, Pfs230, Pfs47, and Pfs28 exhibit minimal diversity and no immune selection in epitopes that induce strain-transcending antibodies, suggesting potential effectiveness of 3D7-based vaccines in blocking transmission.
Interpretation: These findings offer valuable insights into the selection of optimal vaccine candidates against P. falciparum. Based on our results, we recommend prioritising conserved merozoite antigens and transmission-blocking antigens. Combining these antigens in multi-stage approaches may be particularly promising for malaria vaccine development initiatives.
Funding: Purdue Department of Biological Sciences; Puskas Memorial Fellowship; National Institute of Allergy and Infectious Diseases (U19AI089680).
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663769 | PMC |
| http://dx.doi.org/10.1016/j.ebiom.2024.105227 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Designing a multi-epitope vaccine against the midgut-specific fibrinogen-related protein 1(FREP1) of Anopheles stephensi to enhance protection against the malaria parasite: a step beyond traditional vaccine development approaches.
Biotechnol Lett
September 2025
Department of Genetics, Maharshi Dayanand University, Rohtak, Haryana, 124001, India.
Malaria has been a prominent health burden for decades globally. The complex life cycle of Plasmodium made numerous challenges in finding an effective candidate for developing a potent transmission-blocking vaccine (TBV) against malaria. A wide variety of genes of Anopheles mosquitoes' midgut and salivary gland play a pivotal role in the Plasmodium invasion and transmission inside the mosquito body.
View Article and Find Full Text PDFA combined designed CSP and Pfs48/45 infection and transmission blocking vaccine for malaria.
NPJ Vaccines
September 2025
Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
The multiple stages of the malaria parasite life cycle hampers vaccine development. Combining a pre-erythrocytic antigen with a transmission-blocking antigen would target two independent stages of the life cycle for disease control, resulting in a multistage vaccine that can prevent infection and disease transmission simultaneously. Here, we generated a self-assembled ferritin nanoparticle vaccine that simultaneously presents designed immunogens CSPj5c and 17-4 from the infection-blocking circumsporozoite and the transmission-blocking Pfs48/45 antigens.
View Article and Find Full Text PDFWhy the Jenner/Pasteur paradigm is insufficient for controlling vector-borne diseases and the role of microbiota-mediated interactions.
Curr Res Parasitol Vector Borne Dis
July 2025
Anses, INRAE, Ecole Nationale Vétérinaire d'Alfort, UMR BIPAR, Laboratoire de Santé Animale, Maisons-Alfort, F-94700, France.
Vaccination campaigns have profoundly influenced the dynamics of infectious diseases, acting as one of the largest ecological experiments in history. By vaccinating billions across decades, we have imposed powerful selective pressures on pathogens, illuminating their ability to adapt, evade, or persist. Rooted in the Jenner/Pasteur paradigm - where exposure to an antigen induces protective immunity - vaccines have revealed how pathogens differ in their ecological susceptibility to immunity.
View Article and Find Full Text PDFPriming or Boosting P. falciparum Transmission Blocking Responses with Recombinant Vaccines or Gametocyte Extract.
J Infect Dis
June 2025
Department of Biomedical Engineering, State University of New York at Buffalo, Buffalo, NY 14260, USA.
P. falciparum infection can induce antibody responses to the parasitic, gametocyte-expressed antigens Pfs48/45 and Pfs230. Retrospective analysis of healthy individuals from malaria-endemic Mali showed increasing prevalence of antibodies to these antigens from infancy to age 17, an expected response to malaria exposure.
View Article and Find Full Text PDFStructural elucidation of full-length Pfs48/45 in complex with potent monoclonal antibodies isolated from a naturally exposed individual.
Nat Struct Mol Biol
August 2025
Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
Biomedical interventions that block the transmission of Plasmodium falciparum (Pf) from humans to mosquitoes may be critical for malaria elimination. Pfs48/45, a gamete-surface protein essential for Pf development in the mosquito midgut, is a target of clinical-stage transmission-blocking vaccines and monoclonal antibodies (mAbs) that disrupt Pf transmission to mosquitoes. Antibodies directed to domain 3 of Pfs48/45 have been structurally and functionally described; however, in-depth information about other inhibitory epitopes on Pfs48/45 is currently limited.
View Article and Find Full Text PDF