title: Impact of exposure to mosquito transmission-blocking antibodies on Plasmodium falciparum population genetic structure.
abstract: 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 FISand multiplicity of infection. Treatments also resulted in significant decrease in FISas 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.
authors: UMR MIVEGEC, IRD 224-CNRS 5290-UM, Institut de Recherche pour le Développement, 911 avenue Agropolis, 34394 Montpellier, France; Laboratoire d'entomologie médicale, Organisation de Coordination et de Coopération pour la Lutte Contre les Grandes Endémies en Afrique Centrale, Yaoundé, Cameroon. Electronic address: marcel.sandeu@ird.fr.
authors: Maurice M
authors: MM
authors: Sandeu
authors: UMR MIVEGEC, IRD 224-CNRS 5290-UM, Institut de Recherche pour le Développement, 911 avenue Agropolis, 34394 Montpellier, France. Electronic address: luc.abate@ird.fr.
authors: Luc
authors: L
authors: Abate
authors: UMR MIVEGEC, IRD 224-CNRS 5290-UM, Institut de Recherche pour le Développement, 911 avenue Agropolis, 34394 Montpellier, France. Electronic address: majoline.tchioffo@ird.fr.
authors: Majoline T
authors: MT
authors: Tchioffo
authors: Laboratoire d'entomologie médicale, Organisation de Coordination et de Coopération pour la Lutte Contre les Grandes Endémies en Afrique Centrale, Yaoundé, Cameroon. Electronic address: nganobayi@gmail.com.
authors: Albert N
authors: AN
authors: Bayibéki
authors: Laboratoire d'entomologie médicale, Organisation de Coordination et de Coopération pour la Lutte Contre les Grandes Endémies en Afrique Centrale, Yaoundé, Cameroon. Electronic address: hpaawono@yahoo.fr.
authors: Parfait H
authors: PH
authors: Awono-Ambéné
authors: Laboratoire d'entomologie médicale, Organisation de Coordination et de Coopération pour la Lutte Contre les Grandes Endémies en Afrique Centrale, Yaoundé, Cameroon; Université de Douala, Faculté de Médecine et des Sciences Pharmaceutiques, BP 2701, Douala, Cameroon. Electronic address: nsango2013@yahoo.fr.
authors: Sandrine E
authors: SE
authors: Nsango
authors: UMI TransVIHMI 233, IRD 233-INSERM 1175-UM, Institut de Recherche pour le Développement, 911 avenue Agropolis, 34394 Montpellier, France. Electronic address: cedric.chesnais@ird.fr.
authors: Cédric B
authors: CB
authors: Chesnais
authors: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Emerging Pathogens Institute, Department of Infectious Diseases and Pathology, University of Florida, Gainesville, FL, USA. Electronic address: rdinglasan@epi.ufl.edu.
authors: Rhoel R
authors: RR
authors: Dinglasan
authors: UMR 177 IRD-CIRAD INTERTRYP, TA A-17/G, Campus International de Baillarguet, 34398 Montpellier Cedex5, France. Electronic address: thierry.demeeus@ird.fr.
authors: Thierry
authors: T
authors: de Meeûs
authors: UMR MIVEGEC, IRD 224-CNRS 5290-UM, Institut de Recherche pour le Développement, 911 avenue Agropolis, 34394 Montpellier, France; Laboratoire d'entomologie médicale, Organisation de Coordination et de Coopération pour la Lutte Contre les Grandes Endémies en Afrique Centrale, Yaoundé, Cameroon. Electronic address: isabelle.morlais@ird.fr.
authors: Isabelle
authors: I
authors: Morlais
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology*; D019138:Antibodies, Blocking / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005828:Genetics, Population; D006801:Humans; D017780:Malaria Vaccines; D016778:Malaria, Falciparum / Q000517:prevention & control* / Q000635:transmission*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D017780:Malaria Vaccines
keywords: Anopheles coluzzii; Anti-AnAPN1 antibodies; Genetic structure; Multiplicity of infection; Plasmodium falciparum; Sib-mating