TY - JOUR
T1 - Impact of exposure to mosquito transmission-blocking antibodies on Plasmodium falciparum population genetic structure
AU - Sandeu, Maurice M.
AU - Abate, Luc
AU - Tchioffo, Majoline T.
AU - Bayibéki, Albert N.
AU - Awono-Ambéné, Parfait H.
AU - Nsango, Sandrine E.
AU - Chesnais, Cédric B.
AU - Dinglasan, Rhoel R.
AU - de Meeûs, Thierry
AU - Morlais, Isabelle
N1 - Funding Information:
This work was supported by funds from the Institut de Recherche pour le Développement (IRD) and the UE-ERC Malares (grant agreement 260918 ). We are grateful to volunteers from Mfou primary schools and their parents or guardians for participating in this study, to the medical team from the Mfou Hospital for assistance in the field and to the technician staff from the IRD-OCEAC laboratory for P. falciparum infections and mosquito dissections. MMS was supported by a fellowship from the IRD.
Publisher Copyright:
© 2016
PY - 2016/11/1
Y1 - 2016/11/1
N2 - Progress in malaria control has led to a significant reduction of the malaria burden. Interventions that interrupt transmission are now needed to achieve the elimination goal. Transmission-blocking vaccines (TBV) that aim to prevent mosquito infections represent promising tools and several vaccine candidates targeting different stages of the parasite's lifecycle are currently under development. A mosquito-midgut antigen, the anopheline alanyl aminopeptidase (AnAPN1) is one of the lead TBV candidates; antibodies against AnAPN1 prevent ookinete invasion. In this study, we explored the transmission dynamics of Plasmodium falciparum in mosquitoes fed with anti-AnAPN1 monoclonal antibodies (mAbs) vs. untreated controls, and investigated whether the parasite genetic content affects or is affected by antibody treatment. Exposure to anti-AnAPN1 mAbs was efficient at blocking parasite transmission and the effect was dose-dependent. Genetic analysis revealed a significant sib-mating within P. falciparum infra-populations infecting one host, as measured by the strong correlation between Wright's FIS and multiplicity of infection. Treatments also resulted in significant decrease in FIS as a by-product of drop in infra-population genetic diversity and concomitant increase of apparent panmictic genotyping proportions. Genetic differentiation analyses indicated that mosquitoes fed on a same donor randomly sampled blood-circulating gametocytes. We did not detect trace of selection, as the genetic differentiation between different donors did not decrease with increasing mAb concentration and was not significant between treatments for each gametocyte donor. Thus, there is apparently no specific genotype associated with the loss of diversity under mAb treatment. Finally, the anti-AnAPN1 mAbs were effective at reducing mosquito infection and a vaccine aiming at eliciting anti-AnAPN1 mAbs has a strong potential to decrease the burden of malaria in transmission-blocking interventions without any apparent selective pressure on the parasite population.
AB - Progress in malaria control has led to a significant reduction of the malaria burden. Interventions that interrupt transmission are now needed to achieve the elimination goal. Transmission-blocking vaccines (TBV) that aim to prevent mosquito infections represent promising tools and several vaccine candidates targeting different stages of the parasite's lifecycle are currently under development. A mosquito-midgut antigen, the anopheline alanyl aminopeptidase (AnAPN1) is one of the lead TBV candidates; antibodies against AnAPN1 prevent ookinete invasion. In this study, we explored the transmission dynamics of Plasmodium falciparum in mosquitoes fed with anti-AnAPN1 monoclonal antibodies (mAbs) vs. untreated controls, and investigated whether the parasite genetic content affects or is affected by antibody treatment. Exposure to anti-AnAPN1 mAbs was efficient at blocking parasite transmission and the effect was dose-dependent. Genetic analysis revealed a significant sib-mating within P. falciparum infra-populations infecting one host, as measured by the strong correlation between Wright's FIS and multiplicity of infection. Treatments also resulted in significant decrease in FIS as a by-product of drop in infra-population genetic diversity and concomitant increase of apparent panmictic genotyping proportions. Genetic differentiation analyses indicated that mosquitoes fed on a same donor randomly sampled blood-circulating gametocytes. We did not detect trace of selection, as the genetic differentiation between different donors did not decrease with increasing mAb concentration and was not significant between treatments for each gametocyte donor. Thus, there is apparently no specific genotype associated with the loss of diversity under mAb treatment. Finally, the anti-AnAPN1 mAbs were effective at reducing mosquito infection and a vaccine aiming at eliciting anti-AnAPN1 mAbs has a strong potential to decrease the burden of malaria in transmission-blocking interventions without any apparent selective pressure on the parasite population.
KW - Anopheles coluzzii
KW - Anti-AnAPN1 antibodies
KW - Genetic structure
KW - Multiplicity of infection
KW - Plasmodium falciparum
KW - Sib-mating
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U2 - 10.1016/j.meegid.2016.08.025
DO - 10.1016/j.meegid.2016.08.025
M3 - Article
C2 - 27566334
AN - SCOPUS:84985006615
SN - 1567-1348
VL - 45
SP - 138
EP - 144
JO - Infection, Genetics and Evolution
JF - Infection, Genetics and Evolution
ER -