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Spatiotemporal Dynamic of the RTS,S/AS01 Malaria Vaccine Target Antigens in Senegal

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  • 1 Department of Parasitology and Mycology, Cheikh Anta Diop University, Dakar, Senegal;
  • | 2 Aristide Le Dantec University Hospital, Dakar, Senegal;
  • | 3 Aix Marseille University, IRD, AP-HM, SSA, VITROME, Marseille, France;
  • | 4 IHU Méditerranée Infection, Marseille, France;
  • | 5 National Malaria Control Program (NMCP), Dakar, Senegal

ABSTRACT.

The RTS,S/AS01 malaria vaccine confers only moderate protection against malaria. Evidence suggests that the effectiveness of the RTS,S/AS01 vaccine depends upon the parasite population genetics, specifically regarding the circumsporozoite protein haplotypes in the population. We investigated Plasmodium falciparum circumsporozoite protein (PfCSP) gene sequences from two endemic sites in 2018 in Senegal. The PfCSP sequences were compared with those retrieved from the Pf3k genome database. In the central repeat region of PfCSP, the distribution of haplotypes differed significantly between the two study sites (Fisher’s exact test, P < 0.001). No 3D7 vaccine strain haplotype was observed in this locus. In the C-terminal region, there was no significant difference in haplotypes distribution between Kedougou and Diourbel (Fischer’s exact test, P = 0.122). The 3D7 haplotype frequency was 8.4% in early samples (2001–2011), but then it contracted in the subsequent years. The extensive plasticity of the P. falciparum genes coding the RTS,S/AS01 vaccine target antigens may influence the immune responses to circulating alleles. Monitoring the genetic diversity baseline and its dynamics over time and space would be instrumental in rationally improving the malaria RTS,S/AS01 vaccine and/or its implementation schedule.

Author Notes

Address correspondence to Mamadou Alpha Diallo, Department of Parasitology and Mycology, Cheikh Anta Diop University, Dakar, Senegal. E-mail: mamadoualpha.diallo@ucad.edu.sn

Financial support: Funding for this TES was provided by the US President's Malaria Initiative. Partial support also came from a PhD fellowship granted by the French Ministry or Foreign affairs (Ministère des Affaires Etrangères). PCR and sequencing were supported by the French Government under the Investissements d'Avenir (Investments for the Future) program managed by the Agence Nationale de la Recherche (ANR, fr: National Agency for Research), (reference: Méditerranée Infection 10-IAHU-03), the IHU-Méditerranée Infection Foundation.

Authors’ addresses: Mamadou Alpha Diallo, Khadim Diongue, Aida Sadikh Badiane, Mouhamad Sy, Mame Cheikh Seck, Mouhamadou Ndiaye, and Daouda Ndiaye, Department of Parasitology and Mycology, Cheikh Anta Diop University, Dakar, Senegal, and Aristide Le Dantec University Hospital, Dakar, Senegal, E-mails: mamadoualpha.diallo@ucad.edu.sn, khadimase@gmail.com, asbadiane@gmail.com, symouhamad92@gmail.com, mcseck203@yahoo.fr, mouhamadou.ndiaye@ucad.edu.sn, and daouda.ndiaye@ucad.edu.sn. Aly Kodio, Aix Marseille University, IRD, AP-HM, SSA, VITROME, Marseille, France, and IHU Méditerranée Infection, Marseille, France, E-mail: alkodio@icermali.org. Mamadou Lamine Tall, Aix Marseille University, IRD, AP-HM, SSA, VITROME, Marseille, France, E-mail: laminetall30@gmail.com. Doudou Sene, IHU Méditerranée Infection, Marseille, France, E-mail: drdocsene@yahoo.fr. Fatou Ba Fall, National Malaria Control Program (NMCP), Dakar, Senegal, E-mail: fall1fatou@yahoo.fr. Stéphane Ranque, Aix Marseille University, IRD, AP-HM, SSA, VITROME, Marseille, France, and IHU Méditerranée Infection, Marseille, France, E-mail: Stephane.RANQUE@ap-hm.fr.

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