Plasmodium falciparum-Specific Memory B-Cell and Antibody Responses Are Associated With Immunity in Children Living in an Endemic Area of Kenya Peter Jahnmatz 1,2 * , Diana Nyabundi 3 , Christopher Sundling 1,4 , Linnea Widman 5 , Jedidah Mwacharo 3 , Jennifer Musyoki 3 , Edward Otieno 3 , Niklas Ahlborg 2,6 , Philip Bejon 3 , Francis M. Ndungu 3,1,7 * † and Anna Färnert 1,4 * † 1 Division of Infectious Diseases, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden, 2 Mabtech AB, Nacka Strand, Sweden, 3 KEMRI - Wellcome Research Programme/Centre for Geographical Medicine Research (Coast), Kilifi, Kenya, 4 Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden, 5 Division of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, 6 Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden, 7 Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, United Kingdom Identifying the mechanism of naturally acquired immunity against Plasmodium falciparum malaria could contribute to the design of effective malaria vaccines. Using a recently developed multiplexed FluoroSpot assay, we assessed cross-sectional pre-existing memory B-cells (MBCs) and antibody responses against six well known P. falciparum antigens (MSP-1 19 , MSP-2 (3D7), MSP-2 (FC27), MSP-3, AMA-1 and CSP) and measured their associations with previous infections and time to clinical malaria in the ensuing malaria season in Kenyan children. These children were under active weekly surveillance for malaria as part of a long-term longitudinal malaria immunology cohort study, where they are recruited from birth. After performing Cox regression analysis, we found that children with a breadth of three or more antigen-specific MBC or antibody responses at the baseline had a reduced risk for malaria in the ensuing P. falciparum transmission season. Specifically, MBC responses against AMA-1, MSP-2 (3D7) and MSP-3, as well as antibody responses to MSP-2 (3D7) and MSP-3 were prospectively associated with a reduced risk for malaria. The magnitude or breadth of MBC responses were however not correlated with the cumulative number of malaria episodes since birth. We conclude that increased breadth for merozoite antigen-specific MBC and antibody responses is associated with protection against malaria. Keywords: P.falciparum malaria, recombinant antigens, memory B-cells, antibodies, FluoroSpot Frontiers in Immunology | www.frontiersin.org March 2022 | Volume 13 | Article 799306 1 Edited by: Leonardo Jose de Moura Carvalho, Oswaldo Cruz Foundation (Fiocruz), Brazil Reviewed by: Lisa Ioannidis, Walter and Eliza Hall Institute of Medical Research, Australia Issiaka SOULAMA, Research Institute for Health Sciences (IRSS), Burkina Faso *Correspondence: Francis M. Ndungu FNdungu@kemri-wellcome.org Anna Färnert anna.farnert@ki.se Peter Jahnmatz peter.jahnmatz@ki.se † These authors have contributed equally to this work Specialty section: This article was submitted to Parasite Immunology, a section of the journal Frontiers in Immunology Received: 21 October 2021 Accepted: 16 February 2022 Published: 09 March 2022 Citation: Jahnmatz P, Nyabundi D, Sundling C, Widman L, Mwacharo J, Musyoki J, Otieno E, Ahlborg N, Bejon P, Ndungu FM and Färnert A (2022) Plasmodium falciparum-Specific Memory B-Cell and Antibody Responses Are Associated With Immunity in Children Living in an Endemic Area of Kenya. Front. Immunol. 13:799306. doi: 10.3389/fimmu.2022.799306 ORIGINAL RESEARCH published: 09 March 2022 doi: 10.3389/fimmu.2022.799306