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Table 2 Association between RTS,S-induced antibody responses and protection against clinical malaria

From: Baseline exposure, antibody subclass, and hepatitis B response differentially affect malaria protective immunity following RTS,S/AS01E vaccination in African children

   Univariate
All subjects
Multivariable
All subjects
Multivariable
Subjects age < 10 months
Antibody Antigen OR 95%CI p OR 95%CI p Covariates* OR 95%CI P Covariates**
IgG M3 CSP FL 0.74 0.41; 1.23 0.25     Age, site, exposure     Age, site, exposure
CSP C-term 0.58 0.28; 1.05 0.21 0.6 0.26; 1.18 0.17 Age, site, M0, exposure     Age, site, M0, exposure
CSP NANP 0.67 0.37; 1.08 0.21     Age, site, M0     Age, site
HBsAg 0.50 0.29; 0.82 0.02 0.38 0.2; 0.7 0.002 Site, exposure 0.42 0.18; 0.9 0.03 Site, M0, exposure, maternal
IgM M3 CSP FL 0.94 0.5; 1.75 1     Age, site, exposure     Age, site, M0
CSP C-term 1.09 0.49; 2.44 1     Age, site, exposure     Age, site, M0
CSP NANP 0.79 0.43; 1.44 1     Age, site, exposure     Age, site, M0
HBsAg 0.46 0.25; 0.82 0.03     Site, M0, exposure     Site, M0, exposure
IgG1 M3 CSP FL 0.86 0.52; 1.36 0.54     Age, site, exposure     Age, site, exposure
CSP C-term 0.60 0.34; 0.97 0.09 0.64 0.36; 1.06 0.1 Age, site, exposure     Age, site, M0, exposure
CSP NANP 0.83 0.53; 1.25 0.48     Age, site, M0, exposure     Age, site, M0, exposure
HBsAg 0.58 0.35; 0.92 0.057 0.49 0.27; 0.85 0.01 Site, exposure     Age, site, exposure
IgG2 M3 CSP FL 4.38 1.75; 12.29 0.006     Age, site     Site, maternal
CSP C-term 4.08 2.07; 8.79 <0.001 2.62 1.18; 6.11 0.02 Site, sex 2.69 1.09; 7.32 0.04 Maternal, site, sex
CSP NANP 2.63 1.2; 6.25 0.049     Age, site     Maternal, site
HBsAg 0.76 0.37; 1.49 0.49     Age, site     Maternal, site
IgG3 M3 CSP FL 0.88 0.56; 1.35 0.54     Age, site, exposure     Age, site, exposure
CSP C-term 0.75 0.44; 1.26 0.46     Age, site, exposure     Age, site, exposure
CSP NANP 0.81 0.53; 1.21 0.46 0.63 0.38; 1.02 0.07 Age, site, exposure     Age, site, exposure
HBsAg 0.19 0.06; 0.51 0.004 0.1 0.02; 0.34 <0.001 Site, exposure 0.26 0.06; 0.92 0.05 Site, maternal, exposure
IgG4 M3 CSP FL 2.15 1.31; 3.66 0.009     Age, site, exposure     Age, site, exposure
CSP C-term 1.27 0.79; 2.04 0.46 1.63 0.92; 3 0.1 Age, site     Age, site, exposure
CSP NANP 1.27 0.74; 2.24 0.48     Age, site, M0, exposure     Age, site, exposure
HBsAg 0.11 0.01; 1.51 0.20     Age, site, exposure     Age, site, exposure
IgG M3–M0 CSP FL 0.47 0.27; 0.73 0.001     Age, site, exposure     Age, site, exposure
CSP C-term 0.36 0.18; 0.65 0.001 0.51 0.26; 0.88 0.03 Age, site, exposure     Age, site, exposure
CSP NANP 0.55 0.35; 0.8 0.003 0.72 0.46; 1.06 0.11 Age, site, exposure     Age, site, exposure
HBsAg 0.73 0.49; 1.07 0.11     Age, site, exposure     Age, site, exposure
IgM M3–M0 CSP FL 0.72 0.43; 1.18 0.38     Age, site, exposure     Age, site, exposure
CSP C-term 0.64 0.36; 1.11 0.35     Age, site, exposure     Site, maternal
CSP NANP 0.62 0.38; 0.97 0.14     Age, site, exposure     Age, site, exposure
HBsAg 0.79 0.42; 1.41 0.42     Age, site, exposure     Age, site, exposure
IgG1 M3–M0 CSP FL 0.52 0.33; 0.76 0.007     Age, site, exposure     Age, site, exposure
CSP C-term 0.54 0.33; 0.81 0.01 0.63 0.39; 0.96 0.04 Age, site, exposure 0.66 0.4; 1.02 0.07 Age, site, exposure
CSP NANP 0.63 0.44; 0.86 0.01 0.75 0.52; 1.03 0.08 Age, site, exposure 0.78 0.54; 1.08 0.14 Age, site, exposure
HBsAg 0.73 0.51; 1.05 0.19     Age, site, exposure     Age, site, exposure
IgG2 M3–M0 CSP FL 0.72 0.41; 1.21 0.34     Age, site     Site, maternal
CSP C-term 2.30 1.29; 4.33 0.02 1.86 0.95; 3.81 0.08 Site, sex 2.46 1.1; 6.13 0.04 Site, maternal, sex
CSP NANP 0.86 0.52; 1.43 0.60     Age, site     Site, maternal
HBsAg 1.32 0.65; 2.73 0.56     Age, site     Site, maternal
IgG3 M3–M0 CSP FL 0.65 0.45; 0.91 0.03 0.77 0.52; 1.11 0.16 Age, site, exposure     Age, site, exposure
CSP C-term 0.79 0.53; 1.17 0.35     Age, site, exposure     Age, site, exposure
CSP NANP 0.72 0.53; 0.97 0.07 0.73 0.52; 1.02 0.07 Age, site, exposure     Age, site, exposure
HBsAg 0.76 0.48; 1.16 0.34     Age, site, exposure     Age, site, exposure
IgG4 M3–M0 CSP FL 1.67 1.08; 2.66 0.053     Age, site, exposure     Age, site, exposure
CSP C-term 1.15 0.78; 1.71 0.56 1.44 0.9; 2.37 0.14 Age, site     Age, site, exposure
CSP NANP 1.19 0.75; 1.9 0.56     Age, site, exposure     Age, site, exposure
HBsAg 0.78 0.08; 7.09 0.82     Age, site, exposure 18.1 0.57;967 0.11 Age, site, exposure
IgG1 + IgG3/IgG2 + IgG4 M3 CSP FL 0.01 0; 0.12 <0.001 0.11 0.01; 1.9 0.13 Age, site     Site, maternal
CSP C-term 0.03 0; 0.22 0.002 0.03 0; 0.35 0.007 Site, sex 0.04 0; 0.79 0.04 Site, maternal, sex
CSP NANP 0.06 0; 0.82 0.07 0.06 0; 1.26 0.07 Age, site, exposure     Site, maternal
HBsAg 0.07 0; 1.14 0.07 0 0; 0.15 0.004 Site, exposure     Site, maternal
  1. Logistic regression models of the association between (i) levels of antibodies (log10MFI) at month (M) 3, (ii) increments from M0 to M3 antibodies (iii), ratio of cytophilic to non-cytophilic antibodies at M3, and clinical malaria (yes/no), in RTS,S/AS01E vaccinees, expressed as odds ratio (OR), 95% confidence interval (CI), and p values (corrected for multiple comparisons, see the “Methods” section). The associations between predictors and outcome shown here were not found in comparator vaccines at month 3 (data not shown). Multivariable analysis models were done with the minimum Akaike information criterion (AIC); statistically significant variables are marked in italics. A combination of backward and forward stepwise algorithms was used to obtain the model with the minimum AIC.
  2. *Variables that were statistically significant (italics) or improved the multivariable model. Exposure = malaria exposure antibody index, age in weeks; M0 = baseline antibody levels to the respective antigen/Ig
  3. **Analyses included also antimalarial maternal antibody index (maternal)