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Development of high affinity antibodies to Plasmodium falciparum merozoite and sporozoite antigens during infancy and adulthood

Lugaajju, Allan ; Idro, Richard ; Kiwuwa, Stephen ; Beeson, James G. ; Drew, Damien R. ; Mortazavi, Susanne E. LU orcid ; Linse, Sara LU and Persson, Kristina E.M. LU (2025) In Frontiers in Immunology 16.
Abstract

Antibodies are important for protection against malaria. For optimal protective activity, it is thought that antibodies need to have high affinity. A longitudinal study conducted in Uganda followed newborn infants and their mothers for nine months. The study found that antibody affinity (here measured as dissociation rate constant, kd) against the merozoite antigens AMA1 and MSP2 decreased from birth to six months in the infants, then gradually increased to 9 months, but not reaching the level observed in the mothers. In contrast, affinity against the sporozoite antigen CSP, did not change throughout the study period. Among mothers, no significant changes in antibody affinity were observed for any antigen, which is consistent... (More)

Antibodies are important for protection against malaria. For optimal protective activity, it is thought that antibodies need to have high affinity. A longitudinal study conducted in Uganda followed newborn infants and their mothers for nine months. The study found that antibody affinity (here measured as dissociation rate constant, kd) against the merozoite antigens AMA1 and MSP2 decreased from birth to six months in the infants, then gradually increased to 9 months, but not reaching the level observed in the mothers. In contrast, affinity against the sporozoite antigen CSP, did not change throughout the study period. Among mothers, no significant changes in antibody affinity were observed for any antigen, which is consistent with expectations for adults in an endemic area. Comparing specific antibody affinities to total antibody levels revealed almost no correlations, indicating that antibody magnitude and affinity evolve differently during immune development. Significant correlations were observed between antibody affinities and some atypical memory B cells. In conclusion, our study shows that development of naturally acquired slowly dissociating (high affinity) antibodies against malaria can evolve separately across different antigens. This is important information for future vaccine development studies.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
affinity, AMA1, antibodies, CSP, falciparum, malaria, MSP2
in
Frontiers in Immunology
volume
16
article number
1562671
publisher
Frontiers Media S. A.
external identifiers
  • scopus:105010922940
  • pmid:40672955
ISSN
1664-3224
DOI
10.3389/fimmu.2025.1562671
language
English
LU publication?
yes
additional info
Publisher Copyright: Copyright © 2025 Lugaajju, Idro, Kiwuwa, Beeson, Drew, Mortazavi, Linse and Persson.
id
151b6885-8c9b-41d5-941e-5e08295fd46f
date added to LUP
2026-01-08 14:56:04
date last changed
2026-01-09 03:00:08
@article{151b6885-8c9b-41d5-941e-5e08295fd46f,
  abstract     = {{<p>Antibodies are important for protection against malaria. For optimal protective activity, it is thought that antibodies need to have high affinity. A longitudinal study conducted in Uganda followed newborn infants and their mothers for nine months. The study found that antibody affinity (here measured as dissociation rate constant, k<sub>d</sub>) against the merozoite antigens AMA1 and MSP2 decreased from birth to six months in the infants, then gradually increased to 9 months, but not reaching the level observed in the mothers. In contrast, affinity against the sporozoite antigen CSP, did not change throughout the study period. Among mothers, no significant changes in antibody affinity were observed for any antigen, which is consistent with expectations for adults in an endemic area. Comparing specific antibody affinities to total antibody levels revealed almost no correlations, indicating that antibody magnitude and affinity evolve differently during immune development. Significant correlations were observed between antibody affinities and some atypical memory B cells. In conclusion, our study shows that development of naturally acquired slowly dissociating (high affinity) antibodies against malaria can evolve separately across different antigens. This is important information for future vaccine development studies.</p>}},
  author       = {{Lugaajju, Allan and Idro, Richard and Kiwuwa, Stephen and Beeson, James G. and Drew, Damien R. and Mortazavi, Susanne E. and Linse, Sara and Persson, Kristina E.M.}},
  issn         = {{1664-3224}},
  keywords     = {{affinity; AMA1; antibodies; CSP; falciparum; malaria; MSP2}},
  language     = {{eng}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Immunology}},
  title        = {{Development of high affinity antibodies to Plasmodium falciparum merozoite and sporozoite antigens during infancy and adulthood}},
  url          = {{http://dx.doi.org/10.3389/fimmu.2025.1562671}},
  doi          = {{10.3389/fimmu.2025.1562671}},
  volume       = {{16}},
  year         = {{2025}},
}