Imperial College London
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ProfessorThomasChurcher

Faculty of Medicine, School of Public Health

Professor of Infectious Disease Dynamics
 
 
 
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Contact

 

thomas.churcher

 
 
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Location

 

G35Medical SchoolSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{de:2021:10.1038/s41541-021-00366-9,
author = {de, Jong RM and Meerstein-Kessel, L and Da, DF and Nsango, S and Challenger, JD and van, de Vegte-Bolmer M and van, Gemert G-J and Duarte, E and Teyssier, N and Sauerwein, RW and Churcher, TS and Dabire, RK and Morlais, I and Locke, E and Huynen, MA and Bousema, T and Jore, MM},
doi = {10.1038/s41541-021-00366-9},
journal = {npj Vaccines},
pages = {1--9},
title = {Monoclonal antibodies block transmission of genetically diverse Plasmodium falciparum strains to mosquitoes},
url = {http://dx.doi.org/10.1038/s41541-021-00366-9},
volume = {6},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Malaria parasite transmission to mosquitoes relies on the uptake of sexual stage parasites during a blood meal and subsequent formation of oocysts on the mosquito midgut wall. Transmission-blocking vaccines (TBVs) and monoclonal antibodies (mAbs) target sexual stage antigens to interrupt human-to-mosquito transmission and may form important tools for malaria elimination. Although most epitopes of these antigens are considered highly conserved, little is known about the impact of natural genetic diversity on the functional activity of transmission-blocking antibodies. Here we measured the efficacy of three mAbs against leading TBV candidates (Pfs48/45, Pfs25 and Pfs230) in transmission assays with parasites from naturally infected donors compared to their efficacy against the strain they were raised against (NF54). Transmission-reducing activity (TRA) was measured as reduction in mean oocyst intensity. mAb 45.1 (α-Pfs48/45) and mAb 4B7 (α-Pfs25) reduced transmission of field parasites from almost all donors with IC80 values similar to NF54. Sequencing of oocysts that survived high mAb concentrations did not suggest enrichment of escape genotypes. mAb 2A2 (α-Pfs230) only reduced transmission of parasites from a minority of the donors, suggesting that it targets a non-conserved epitope. Using six laboratory-adapted strains, we revealed that mutations in one Pfs230 domain correlate with mAb gamete surface binding and functional TRA. Our findings demonstrate that, despite the conserved nature of sexual stage antigens, minor sequence variation can significantly impact the efficacy of transmission-blocking mAbs. Since mAb 45.1 shows high potency against genetically diverse strains, our findings support its further clinical development and may inform Pfs48/45 vaccine design.
AU  - de,Jong RM
AU  - Meerstein-Kessel,L
AU  - Da,DF
AU  - Nsango,S
AU  - Challenger,JD
AU  - van,de Vegte-Bolmer M
AU  - van,Gemert G-J
AU  - Duarte,E
AU  - Teyssier,N
AU  - Sauerwein,RW
AU  - Churcher,TS
AU  - Dabire,RK
AU  - Morlais,I
AU  - Locke,E
AU  - Huynen,MA
AU  - Bousema,T
AU  - Jore,MM
DO  - 10.1038/s41541-021-00366-9
EP  - 9
PY  - 2021///
SN  - 2059-0105
SP  - 1
TI  - Monoclonal antibodies block transmission of genetically diverse Plasmodium falciparum strains to mosquitoes
T2  - npj Vaccines
UR  - http://dx.doi.org/10.1038/s41541-021-00366-9
UR  - https://www.nature.com/articles/s41541-021-00366-9
UR  - http://hdl.handle.net/10044/1/91051
VL  - 6
ER  -
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