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Dobaño, Carlota; Sanz, Hèctor; Sorgho, Hermann; Dosoo, David; Mpina, Maximilian; Ubillos, Itziar; Aguilar, Ruth; Ford, Tom; Díez-Padrisa, Núria; Williams, Nana Aba; Ayestaran, Aintzane; Traore, Ousmane; Nhabomba, Augusto J; Jairoce, Chenjerai; Waitumbi, John; Agnandji, Selidji Todagbe; Kariuki, Simon; Abdulla, Salim; Aponte, John J; Mordmüller, Benjamin; Asante, Kwaku Poku; Owusu-Agyei, Seth; Tinto, Halidou; Campo, Joseph J; Moncunill, Gemma; Gyan, Ben; Valim, Clarissa; Daubenberger, Claudia
Nature communications, 05/2019, Volume: 10, Issue: 1Journal Article
RTS,S/AS01E has been tested in a phase 3 malaria vaccine study with partial efficacy in African children and infants. In a cohort of 1028 subjects from one low (Bagomoyo) and two high (Nanoro, Kintampo) malaria transmission sites, we analysed IgG plasma/serum concentration and avidity to CSP (NANP-repeat and C-terminal domains) after a 3-dose vaccination against time to clinical malaria events during 12-months. Here we report that RTS,S/AS01E induces substantial increases in IgG levels from pre- to post-vaccination (p < 0.001), higher in NANP than C-terminus (2855 vs 1297 proportional change between means), and higher concentrations and avidities in children than infants (p < 0.001). Baseline CSP IgG levels are elevated in malaria cases than controls (p < 0.001). Both, IgG magnitude to NANP (hazard ratio 95% confidence interval 0.61 0.48-0.76) and avidity to C-terminus (0.07 0.05-0.90) post-vaccination are significantly associated with vaccine efficacy. IgG avidity to the C-terminus emerges as a significant contributor to RTS,S/AS01E-mediated protection.
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