Fig. 5
Effect of CSP antibody concentration on protection against multiple malaria episodes. Association between continuous anti-CSP IgG responses and the hazard of recurrent clinical malaria events within a 12-month follow-up period. a One unit increase in IgG NANP protects from clinical malaria and is significant (95% confidence interval [CI] excludes 1) in RTS,S/AS01E vaccinees in the beginning of the follow-up period. As times progresses, increased NANP IgG is less protective and becomes not significant (95% CI includes 1) at approximately 120 post-vaccination days. b The hazard ratio (HR) of C-terminus (C-term) IgG and recurrent clinical malaria episodes is shown suggesting that increased C-term IgG is significantly protective from clinical malaria until day 90 in RTS,S/AS01E vaccinees. c Increased avidity index (AI) to NANP and, in d increased AI to C-term, is constantly and significantly associated with a lower risk of clinical malaria in RTS,S/AS01E vaccinees. HRs were estimated in a time-varying proportional hazard model with a HR exponentially varying over time (p-value of Schonfeld residual tests for NANP and C-term IgG was <0.001, thus, rejecting a constant HR). Models for IgG concentrations and AIs also included study sites and age cohort with the following HRs: NANP IgG—HRKintampo = 25 [14,46], HRNanoro = 31 [17,57], HR612 weeks, <180 days = 2.40 (1.39; 4.14) * [0.99 (0.99; 0.99)]Days; HR612 weeks, >180 days = 0.05 (0.02; 0.11) * [1.01 (1.00; 1.01)]Days; C-term IgG—HRKintampo = 20 [11, 35], HRNanoro = 25 [14, 43], HR612 weeks, <180 days = 3.21 (1.90; 5.41) * [0.99 (0.98; 0.99)]Days, HR612 weeks, >180 days = 0.06 (0.03; 0.14) * [1.01 (1.01; 1.01)]Days; NANP AI - HRKintampo = 29 [16, 52], HRNanoro = 37 [21, 68], HR612 weeks = 1.03 [0.91, 1.18]; C-term AI—HRKintampo = 23 [14, 40], HRNanoro = 31 [18, 52], HR612 weeks = 0.98 [0.85, 1.13]
