2026/04/21 by Maria Lara-Escandell, Lina Sánchez, Dídac Macià +24 · 1 voice
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · Medicine · #Blood disorders and treatments #Immune Response and Inflammation #Multiple Sclerosis Research Studies
paper · doi:10.1016/s1473-3099(26)00081-2
openalex publication_date 2026/04/21 · openalex created_date 2026/04/22 · openalex updated_date 2026/07/27
Background The RTS,S/AS01 E malaria vaccine provides partial protection against Plasmodium falciparum , largely mediated by antibodies targeting the circumsporozoite protein. Correlates of protection remain incompletely defined and have focused mainly on peak IgG responses to the immunodominant NANP-repeats, with less known about antibody durability or responses to the C-terminus of circumsporozoite protein. Methods In this observational study, we evaluated IgG responses to NANP-repeat, C-terminus, and full-length circumsporozoite protein constructs at five timepoints before and after primary and booster vaccination, in children aged 5–17 months from six African countries enrolled in the RTS,S/AS01 E phase 3 trial (NCT00866619, 2009–11). Antibody kinetics were analysed with linear regressions, and associations with clinical malaria risk over 1 year with Cox models. Findings Between May 25, 2009, to March 5, 2010, 1292 children were recruited and included for analysis in this study. IgG levels declined more slowly for C-terminus than for NANP-repeat over 17 months after primary vaccination (geometric mean fold change 0·099 [95% CI 0·089–0·110] vs 0·055 [0·048–0·062]; p<0·0001). The booster significantly enhanced C-terminal IgG, exceeding post-primary peak levels (geometric mean fold change 1·98 [95% CI 1·77–2·21]), whereas NANP-repeat responses were restored but remained below post-primary levels (geometric mean fold changes 0·57 [95% CI 0·51–0·63]). Higher circumsporozoite protein IgG levels correlated with reduced malaria risk, particularly during maintenance phases, with stronger associations for C-terminus, which remained independently protective after adjustment for NANP-repeat antibodies (hazard ratio 0·60, 95% CI 0·43–0·83; p=0·0021). After boosting, maintenance but not peak IgG levels correlated with reduced malaria risk. Interpretation IgG to circumsporozoite protein C-terminus are more durable than those to the NANP-repeats. Antibody maintenance emerges as a stronger predictor of RTS,S/AS01 E vaccine efficacy than peak responses. Funding USA National Institute of Allergy and Infectious Diseases, National Institutes of Health; PATH and Malaria Vaccine Initiative; Spanish Ministerio de Economía y Competitividad; Instituto de Salud Carlos III; CERCA programme; and Secretaria d'Universitats i Recerca del Departament d'Empresa i Coneixement, Generalitat de Catalunya.