Abstract: 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.
Relation: https://edoc.unibas.ch/70517/1/20190517105913_5cde77e12b934.pdf; Dobaño, Carlota and Sanz, Hèctor and Sorgho, Hermann and Dosoo, David and Mpina, Maximilian and Ubillos, Itziar and Aguilar, Ruth and Ford, Tom and Díez-Padrisa, Núria and Williams, Nana Aba and Ayestaran, Aintzane and Traore, Ousmane and Nhabomba, Augusto J. and Jairoce, Chenjerai and Waitumbi, John and Agnandji, Selidji Todagbe and Kariuki, Simon and Abdulla, Salim and Aponte, John J. and Mordmüller, Benjamin and Asante, Kwaku Poku and Owusu-Agyei, Seth and Tinto, Halidou and Campo, Joseph J. and Moncunill, Gemma and Gyan, Ben and Valim, Clarissa and Daubenberger, Claudia. (2019) Concentration and avidity of antibodies to different circumsporozoite epitopes correlate with RTS,S/AS01E malaria vaccine efficacy. Nature Communications, 10. p. 2174.; info:pmid/31092823; urn:ISSN:2041-1723
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