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

**Authors:** Allan Lugaajju, Richard Idro, Stephen Kiwuwa, James G. Beeson, Damien R. Drew, Susanne E. Mortazavi, Sara Linse, Kristina E. M. Persson

PMC · DOI: 10.3389/fimmu.2025.1562671 · Frontiers in Immunology · 2025-07-02

## TL;DR

This study shows how antibody affinity against malaria antigens changes in infants and adults, with implications for vaccine development.

## Contribution

The study reveals distinct developmental patterns of antibody affinity against different malaria antigens in infants.

## Key findings

- Infant antibody affinity against AMA1 and MSP2 decreases initially but recovers by 9 months.
- Antibody affinity against CSP remains stable in infants during the study period.
- Antibody affinity correlates with atypical memory B cells but not with total antibody levels.

## 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 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.

## Linked entities

- **Proteins:** ama-1 (DNA-directed RNA polymerase II subunit RPB1), MSP2 (microspore-specific promoter 2), DNAJC5 (DnaJ heat shock protein family (Hsp40) member C5)
- **Diseases:** malaria (MONDO:0005136)
- **Species:** Plasmodium falciparum (taxon 5833)

## Full-text entities

- **Genes:** DNAJC5 (DnaJ heat shock protein family (Hsp40) member C5) [NCBI Gene 80331] {aka CLN4, CLN4B, CSP, DNAJC5A, mir-941-2, mir-941-3}
- **Diseases:** malaria (MESH:D008288)
- **Species:** Plasmodium falciparum (malaria parasite P. falciparum, species) [taxon 5833]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12263619/full.md

## References

93 references — full list in the complete paper: https://tomesphere.com/paper/PMC12263619/full.md

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Source: https://tomesphere.com/paper/PMC12263619