Effect of controlled human Plasmodium falciparum infection on B cell subsets in individuals with different levels of malaria immunity
Year: 2025
Type: article
Abstract: Continuous exposure to Plasmodium falciparum (Pf) has been associated with alterations in B cells. We investigated the effect of controlled human malaria infection (CHMI) on B cell phenotypes in individuals with different Pf immunity status: malaria-naïve, immunized with PfSPZ-CVac and semi-immune (lifelong-exposed) volunteers. Compared to naïve, semi-immune but not vaccinated individuals, had increased baseline frequencies of immature B cells (CD19+CD10+), active naive (IgD+CD27−CD21−) B cells, active atypical (IgD−CD27−CD21−) memory B cells (MBCs), active classical (IgD−CD27+CD21−) MBCs and CD1c+-B cells but lower frequencies of some IgG+-B cells. The frequencies of CD1c+ active atypical MBCs correlated positively with anti-Pf antibodies and negatively with circulating eotaxin levels, while the opposite was observed for IgG+ resting atypical MBCs. During early blood-stage infection (day 11 after CHMI), there was an expansion of resting classical (IgD−CD27+CD21+) MBCs in all three groups. Vaccination, compared to placebo, altered the effect of CHMI on B cells, showing a positive association with resting classical MBCs (β = 0.190, 95%CI 0.011–0.368) and active naïve-PD1+ (β = 0.637, 95%CI 0.058–1.217) frequencies, and a negative one with CD1c+ resting atypical MBCs (β=-0.328, 95%CI -0.621–-0.032). In addition, the sickle cell trait in semi-immune subjects altered the effect of CHMI on several B cells. In conclusion, lifelong but not vaccine exposure to malaria was associated with increased frequencies of multiple B cell subsets, with higher and lower percentages of CD1c and IgG expressing-cells, respectively. A single infection (CHMI) induces changes in B cell frequencies and is modulated by sickle cell trait and malaria-immunity status. Clinical Trials Registration. NCT01624961, NCT02115516, and NCT02237586.
Authors: Pilar Requena, Gloria Patricia Gómez-Pérez, Matthew B. B. McCall, Diana Barrios, Ruth Aguilar, Julia Fernández-Morata, Marta Vidal, Joseph J. Campo, Carla Sanchez, Maria Yazdabankhsh, B. Kim Lee Sim, Stephen L. Hoffman, Peter Kremsner, Bertrand Lell, Benjamin Mordmüller, Carlota Dobaño, Gemma Moncunill
Institutions: Universidad de Granada, Instituto de Investigación Biosanitaria de Granada, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Barcelona Institute for Global Health, Universitat de Barcelona, Radboud University Nijmegen, Erasmus MC, Radboud University Medical Center, Antigen Discovery (United States), Leiden University, Leiden University Medical Center, Sanaria, Centre de Recherche Médicales de Lambaréné, German Center for Infection Research, University of Tübingen, Medical University of Vienna, Centro de Investigación Biomédica en Red Enfermedades Infecciosas
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,090
OpenAlex ID: W4414570655