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Concentration and avidity of antibodies to different circumsporozoite epitopes correlate with RTS,S/AS01E malaria vaccine efficacy

2019; Nature Portfolio; Volume: 10; Issue: 1 Linguagem: Inglês

10.1038/s41467-019-10195-z

2041-1723

Carlota Dobaño, Héctor Sanz, Hermann Sorgho, David Dosoo, Maximilian Mpina, Itziar Ubillos, Ruth Aguilar, Tom Ford, Núria Díez‐Padrisa, Nana Aba Williams, Aintzane Ayestaran, Ousmane Traoré, Augusto Nhabomba, Chenjerai Jairoce, John Waitumbi, Selidji Todagbé Agnandji, Simon Kariuki, Salim Abdulla, John J. Aponte, Benjamin Mordmüller, Kwaku Poku Asante, Seth Owusu‐Agyei, Halidou Tinto, Joseph J. Campo, Gemma Moncunill, Ben Gyan, Clarissa Valim, Claudia Daubenberger,

Hepatitis Viruses Studies and Epidemiology

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.