RTS,S/AS01E immunization increases antibody responses to vaccine-unrelated Plasmodium falciparum antigens associated with protection against clinical malaria in African children: a case-control study

Carlota Dobaño; Itziar Ubillos; Chenjerai Jairoce; Ben Gyan; Marta Vidal; Alfons Jiménez; Rebeca Santano; David Dosoo; Augusto J. Nhabomba; Aintzane Ayestaran; Ruth Aguilar; Nana Aba Williams; Núria Díez-Padrisa; David Lanar; Virander Chauhan; Chetan Chitnis; Sheetij Dutta; Deepak Gaur; Evelina Angov; Kwaku Poku Asante; Seth Owusu-Agyei; Clarissa Valim; Benoit Gamain; Ross L. Coppel; David Cavanagh; James G. Beeson; Joseph J. Campo; Gemma Moncunill

doi:10.1186/s12916-019-1378-6

Table 1 Effect of IgG levels to Plasmodium falciparum antigens on malaria protection

From: RTS,S/AS01E immunization increases antibody responses to vaccine-unrelated Plasmodium falciparum antigens associated with protection against clinical malaria in African children: a case-control study

Antibody	Month 3 IgG levels		Age (5–17 months)		Site (Manhiça)		Baseline IgG levels		WAZ		Vaccine (RTS,S)
Antigen	OR	p	OR	p	OR	p	OR	p	OR	p	OR	p
Group i antigens
MSP1₄₂ 3D7	1.11 (0.7; 1.74)	0.65			0.18 (0.08; 0.39)	< 0.001	1.47 (0.96; 2.28)	0.08
MSP1₄₂ FVO	0.87 (0.57; 1.29)	0.48	0.5 (0.23; 1.04)	0.07	0.13 (0.05; 0.29)	< 0.001	1.47 (1.02;2.15)	0.04	0.78 (0.56; 1.08)	0.13	0.59 (0.28; 1.2)	0.15
EXP1	0.8 (0.47; 1.33)	0.39			0.19 (0.08; 0.43)	< 0.001	1.94 (1.24; 3.12)	0.005	0.75 (0.54; 1.05)	0.1	0.53 (0.25; 1.1)	0.09
AMA1 FVO	1.6 (1.15; 2.27)	0.006			0.13 (0.06; 0.25)	< 0.001
AMA1 3D7	0.98 (0.51; 1.83)	0.94			0.14 (0.07; 0.28)	< 0.001	1.54 (0.93; 2.67)	0.1	0.78 (0.56; 1.08)	0.14	0.56 (0.27; 1.15)	0.12
Group ii antigens
pTRAMP	1.01 (0.51; 2.03)	0.98	0.42 (0.2; 0.85)	0.02	0.12 (0.06; 0.25)	< 0.001	2.18 (1.16; 4.21)	0.02			0.54 (0.26; 1.11)	0.1
EBA175 R2(F2)	0.96 (0.56; 1.64)	0.89	0.49 (0.24; 0.98)	0.047	0.09 (0.04; 0.18)	< 0.001
PfRH1	1.58 (0.79; 3.19)	0.2	0.4 (0.18; 0.83)	0.02	0.11 (0.05; 0.23)	< 0.001			0.79 (0.56; 1.09)	0.15
MSP3 3D7	1.32 (0.77; 2.3)	0.32	0.51 (0.25; 1.02)	0.06	0.1 (0.05; 0.2)	< 0.001
Var2csa DBL3–4	1.03 (0.5;2.1)	0.94	0.5 (0.21; 1.13)	0.1	0.09 (0.04; 0.2)	< 0.001
p41	1.41 (0.64; 3.16)	0.4	0.46 (0.22; 0.94)	0.04	0.1 (0.05; 0.19)	< 0.001
MSP2 FL Dd2	0.89 (0.47; 1.61)	0.71			0.25 (0.11; 0.57)	0.001	2.15 (1.31; 3.67)	0.003	0.76 (0.54; 1.06)	0.11	0.52 (0.25; 1.07)	0.08
MSP2 FL CH150	1.02 (0.57; 1.83)	0.96			0.25 (0.11; 0.58)	0.001	2.05 (1.31; 3.29)	0.002	0.76 (0.54; 1.06)	0.11	0.44 (0.2; 0.92)	0.03
MSP1 Bl2 hybrid	1.11 (0.68; 1.83)	0.67	0.5 (0.24; 0.98)	0.049	0.09 (0.04; 0.19)	< 0.001
MSP3 3C	1.22 (0.74; 2.01)	0.43	0.41 (0.19; 0.84)	0.02	0.1 (0.05; 0.22)	< 0.001	1.67 (0.94; 2.99)	0.08			0.55 (0.27; 1.14)	0.11
PfRH2 b240	1.03 (0.49; 2.18)	0.94	0.49 (0.24; 0.98)	0.049	0.09 (0.04; 0.19)	< 0.001
LSA1	0.88 (0.51; 1.49)	0.64	0.5 (0.24; 0.99)	0.051	0.09 (0.04; 0.18)	< 0.001
MSP1 Bl2 PA17	0.96 (0.53; 1.7)	0.89	0.5 (0.24; 0.98)	0.048	0.09 (0.04; 0.18)	< 0.001
Var2csa DBL1–2	0.9 (0.37; 2.27)	0.82			0.14 (0.07; 0.29)	< 0.001	2.06 (1.01; 4.26)	0.047			0.57 (0.28; 1.16)	0.12
CyRPA	1.81 (0.76; 4.43)	0.18	0.4 (0.18; 0.82)	0.02	0.1 (0.04; 0.19)	< 0.001			0.79 (0.57; 1.09)	0.15	0.57 (0.28; 1.17)	0.13
CelTOS	1.55 (0.77; 3.13)	0.22	0.41 (0.19; 0.85)	0.02	0.1 (0.05; 0.2)	< 0.001			0.79 (0.57; 1.09)	0.16	0.58 (0.28; 1.18)	0.13
RH4.9	0.62 (0.3; 1.26)	0.19	0.53 (0.26; 1.05)	0.07	0.08 (0.04; 0.16)	< 0.001
Group iii antigens
DBL-α	1.35 (0.62; 2.91)	0.44	0.45 (0.21;0.92)	0.03	0.12 (0.05; 0.24)	< 0.001	1.9 (0.88; 4.22)	0.11
RH5	1.93 (0.98; 4.01)	0.07	0.38 (0.17; 0.79)	0.01	0.11 (0.05; 0.21)	< 0.001			0.78 (0.56; 1.08)	0.15	0.51 (0.24; 1.07)	0.08
SSP2 (TRAP)	0.52 (0.26; 0.98)	0.05			0.11 (0.05; 0.23)	< 0.001	2.29 (1.14; 4.8)	0.02
MSP1 Bl2 Mad20	0.61 (0.13; 2.7)	0.52	0.55 (0.26; 1.13)	0.11	0.14 (0.07; 0.3)	< 0.001	5.91 (1.5; 29.52)	0.02	0.79 (0.57; 1.09)	0.15
MSP6	1.19 (0.56; 2.61)	0.65	0.47 (0.21; 0.98)	0.05	0.14 (0.06; 0.3)	< 0.001	1.63 (0.89; 3.01)	0.12	0.78 (0.56; 1.07)	0.12	0.51 (0.23; 1.09)	0.08
RH2 (2030)	1.37 (0.72; 2.65)	0.35	0.51 (0.25; 1.01)	0.059	0.1 (0.04; 0.19)	< 0.001					0.55 (0.26; 1.16)	0.12
EBA175 R3–5	1.17 (0.71; 1.96)	0.54	0.45 (0.21; 0.91)	0.03	0.1 (0.05; 0.2)	< 0.001			0.79 (0.57; 1.09)	0.16	0.55 (0.25; 1.18)	0.13
MSP5	0.78 (0.48; 1.25)	0.3	0.49 (0.23; 1)	0.056	0.12 (0.06; 0.24)	< 0.001	2.06 (1.26; 3.45)	0.005
EBA140 R3–5	1.21 (0.69; 2.14)	0.5	0.47 (0.22; 0.94)	0.04	0.09 (0.04; 0.18)	< 0.001					0.54 (0.24; 1.19)	0.13
MSP1 Bl2 RO33	0.53 (0.3; 0.93)	0.03	0.53 (0.25; 1.07)	0.08	0.1 (0.04; 0.21)	< 0.001	1.64 (0.93; 3.03)	0.1
MSP1 Bl2 Well	0.55 (0.3; 0.99)	0.05	0.51 (0.23; 1.07)	0.08	0.1 (0.05; 0.2)	< 0.001	2.06 (0.95; 4.72)	0.08
MSP1 Bl2 3D7	0.63 (0.39; 1)	0.054	0.47 (0.22; 0.96)	0.042	0.08 (0.04; 0.17)	< 0.001			0.79 (0.56; 1.09)	0.16
RH4.2	0.85 (0.52; 1.38)	0.51	0.53 (0.25; 1.06)	0.08	0.09 (0.04; 0.18)	< 0.001

Each line shows the multivariable logistic regression model’s results with IgG levels to each antigen (expressed as log₁₀ of the median fluorescence intensity measured by quantitative suspension array technology) at month 3 as predictors and clinical malaria as outcome, adjusted by covariates. Columns show the odds ratio (OR) with 95% confidence intervals and p values (significant in italics) of the month 3 IgG levels and the covariables retained in the models for some antigens (in parenthesis the category that is compared to the reference). Variables that were not significant or did not improve the multivariable model are not shown. WAZ weight-for-age Z-score, FL full length, Bl2 block 2

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