Protective near-germline antibodies to malaria elicited by RTS,S/AS01E vaccination in African infants
- 1ISGlobal, Barcelona, Spain
Abstract
Malaria is a leading cause of childhood mortality, yet infant immune responses to vaccination remain poorly understood. Here, we characterize 88 monoclonal antibodies (mAbs) directed against the Plasmodium falciparum circumsporozoite protein cloned from African infants immunized with the RTS,S/AS01E malaria vaccine, identifying potent antiparasitic mAbs exhibiting molecular features resembling those observed in adults and minimal somatic hypermutation. Importantly, germline-reverted variants of four mAbs inducing sterile protection in vivo maintained high binding affinity and Fab-dependent parasite killing. Structural analyses revealed that a few amino acid replacements drive homotypic helical assemblies, fine-tuning parasite inhibition and protective efficacy. Thus, despite maturational constraints of early life, infants can generate potent antimalarial antibodies in a near-germline configuration, informing next-generation vaccine development for this vulnerable group.
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BibTeX
@misc{bloch2026protective,
title = {{Protective near-germline antibodies to malaria elicited by RTS,S/AS01E vaccination in African infants}},
author = {E. Bloch and F. Devys and F. Cannac and M. Jain and K. Broadbent and C. Sanchez and W.-H. Lee and C. Jairoce and P. Aide and J. J. Campo and D. Macia and C. Carolis and I. A. Wilson and A. B. Ward and R. Amino and G. Moncunill and C. Dobano and L. M. Molinos-Albert},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.01.755937},
url = {https://www.biorxiv.org/content/10.64898/2026.10.01.755937v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Protective near-germline antibodies to malaria elicited by RTS,S/AS01E vaccination in African infants
AU - E. Bloch
AU - F. Devys
AU - F. Cannac
AU - M. Jain
AU - K. Broadbent
AU - C. Sanchez
AU - W.-H. Lee
AU - C. Jairoce
AU - P. Aide
AU - J. J. Campo
AU - D. Macia
AU - C. Carolis
AU - I. A. Wilson
AU - A. B. Ward
AU - R. Amino
AU - G. Moncunill
AU - C. Dobano
AU - L. M. Molinos-Albert
PY - 2026
DA - 2026/10/01
PB - bioRxiv
DO - 10.64898/2026.10.01.755937
UR - https://www.biorxiv.org/content/10.64898/2026.10.01.755937v1
AB - Malaria is a leading cause of childhood mortality, yet infant immune responses to vaccination remain poorly understood. Here, we characterize 88 monoclonal antibodies (mAbs) directed against the Plasmodium falciparum circumsporozoite protein cloned from African infants immunized with the RTS,S/AS01E malaria vaccine, identifying potent antiparasitic mAbs exhibiting molecular features resembling those observed in adults and minimal somatic hypermutation. Importantly, germline-reverted variants of four mAbs inducing sterile protection in vivo maintained high binding affinity and Fab-dependent parasite killing. Structural analyses revealed that a few amino acid replacements drive homotypic helical assemblies, fine-tuning parasite inhibition and protective efficacy. Thus, despite maturational constraints of early life, infants can generate potent antimalarial antibodies in a near-germline configuration, informing next-generation vaccine development for this vulnerable group.
ER -