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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)