Differential Patterns of IgG Subclass Responses to Plasmodium falciparum Antigens in Relation to Malaria Protection and RTS,S Vaccination

Carlota Dobaño, Rebeca Santano, Marta Vidal, Alfons Jiménez, Chenjerai Jairoce, Itziar Ubillos, David Dosoo, Ruth Aguilar, Nana Aba Williams, Núria Díez-Padrisa, Aintzane Ayestaran, Clarissa Valim, Kwaku Poku Asante, Seth Owusu-Agyei, David Lanar, Virander Chauhan, Chetan Chitnis, Sheetij Dutta, Evelina Angov, Benoit Gamain & 9 others Ross L. Coppel, James G. Beeson, Linda Reiling, Deepak Gaur, David Cavanagh, Ben Gyan, Augusto J. Nhabomba, Joseph J. Campo, Gemma Moncunill

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Abstract

Naturally acquired immunity (NAI) to Plasmodium falciparum malaria is mainly mediated by IgG antibodies but the subclasses, epitope targets and effector functions have not been unequivocally defined. Dissecting the type and specificity of antibody responses mediating NAI is a key step toward developing more effective vaccines to control the disease. We investigated the role of IgG subclasses to malaria antigens in protection against disease and the factors that affect their levels, including vaccination with RTS,S/AS01E. We analyzed plasma and serum samples at baseline and 1 month after primary vaccination with RTS,S or comparator in African children and infants participating in a phase 3 trial in two sites of different malaria transmission intensity: Kintampo in Ghana and Manhiça in Mozambique. We used quantitative suspension array technology (qSAT) to measure IgG1-4 responses to 35 P. falciparum pre-erythrocytic and blood stage antigens. Our results show that the pattern of IgG response is predominantly IgG1 or IgG3, with lower levels of IgG2 and IgG4. Age, site and RTS,S vaccination significantly affected antibody subclass levels to different antigens and susceptibility to clinical malaria. Univariable and multivariable analysis showed associations with protection mainly for cytophilic IgG3 levels to selected antigens, followed by IgG1 levels and, unexpectedly, also with IgG4 levels, mainly to antigens that increased upon RTS,S vaccination such as MSP5 and MSP1 block 2, among others. In contrast, IgG2 was associated with malaria risk. Stratified analysis in RTS,S vaccinees pointed to novel associations of IgG4 responses with immunity mainly involving pre-erythrocytic antigens upon RTS,S vaccination. Multi-marker analysis revealed a significant contribution of IgG3 responses to malaria protection and IgG2 responses to malaria risk. We propose that the pattern of cytophilic and non-cytophilic IgG antibodies is antigen-dependent and more complex than initially thought, and that mechanisms of both types of subclasses could be involved in protection. Our data also suggests that RTS,S efficacy is significantly affected by NAI, and indicates that RTS,S vaccination significantly alters NAI.

Original languageEnglish
Article number439
Number of pages19
JournalFrontiers in Immunology
Volume10
DOIs
Publication statusPublished - 15 Mar 2019

Keywords

  • antibody
  • children
  • IgG subclass
  • Malaria
  • naturally acquired immunity
  • Plasmodium falciparum
  • protection
  • vaccine

Cite this

Dobaño, Carlota ; Santano, Rebeca ; Vidal, Marta ; Jiménez, Alfons ; Jairoce, Chenjerai ; Ubillos, Itziar ; Dosoo, David ; Aguilar, Ruth ; Williams, Nana Aba ; Díez-Padrisa, Núria ; Ayestaran, Aintzane ; Valim, Clarissa ; Asante, Kwaku Poku ; Owusu-Agyei, Seth ; Lanar, David ; Chauhan, Virander ; Chitnis, Chetan ; Dutta, Sheetij ; Angov, Evelina ; Gamain, Benoit ; Coppel, Ross L. ; Beeson, James G. ; Reiling, Linda ; Gaur, Deepak ; Cavanagh, David ; Gyan, Ben ; Nhabomba, Augusto J. ; Campo, Joseph J. ; Moncunill, Gemma. / Differential Patterns of IgG Subclass Responses to Plasmodium falciparum Antigens in Relation to Malaria Protection and RTS,S Vaccination. In: Frontiers in Immunology. 2019 ; Vol. 10.
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abstract = "Naturally acquired immunity (NAI) to Plasmodium falciparum malaria is mainly mediated by IgG antibodies but the subclasses, epitope targets and effector functions have not been unequivocally defined. Dissecting the type and specificity of antibody responses mediating NAI is a key step toward developing more effective vaccines to control the disease. We investigated the role of IgG subclasses to malaria antigens in protection against disease and the factors that affect their levels, including vaccination with RTS,S/AS01E. We analyzed plasma and serum samples at baseline and 1 month after primary vaccination with RTS,S or comparator in African children and infants participating in a phase 3 trial in two sites of different malaria transmission intensity: Kintampo in Ghana and Manhi{\cc}a in Mozambique. We used quantitative suspension array technology (qSAT) to measure IgG1-4 responses to 35 P. falciparum pre-erythrocytic and blood stage antigens. Our results show that the pattern of IgG response is predominantly IgG1 or IgG3, with lower levels of IgG2 and IgG4. Age, site and RTS,S vaccination significantly affected antibody subclass levels to different antigens and susceptibility to clinical malaria. Univariable and multivariable analysis showed associations with protection mainly for cytophilic IgG3 levels to selected antigens, followed by IgG1 levels and, unexpectedly, also with IgG4 levels, mainly to antigens that increased upon RTS,S vaccination such as MSP5 and MSP1 block 2, among others. In contrast, IgG2 was associated with malaria risk. Stratified analysis in RTS,S vaccinees pointed to novel associations of IgG4 responses with immunity mainly involving pre-erythrocytic antigens upon RTS,S vaccination. Multi-marker analysis revealed a significant contribution of IgG3 responses to malaria protection and IgG2 responses to malaria risk. We propose that the pattern of cytophilic and non-cytophilic IgG antibodies is antigen-dependent and more complex than initially thought, and that mechanisms of both types of subclasses could be involved in protection. Our data also suggests that RTS,S efficacy is significantly affected by NAI, and indicates that RTS,S vaccination significantly alters NAI.",
keywords = "antibody, children, IgG subclass, Malaria, naturally acquired immunity, Plasmodium falciparum, protection, vaccine",
author = "Carlota Doba{\~n}o and Rebeca Santano and Marta Vidal and Alfons Jim{\'e}nez and Chenjerai Jairoce and Itziar Ubillos and David Dosoo and Ruth Aguilar and Williams, {Nana Aba} and N{\'u}ria D{\'i}ez-Padrisa and Aintzane Ayestaran and Clarissa Valim and Asante, {Kwaku Poku} and Seth Owusu-Agyei and David Lanar and Virander Chauhan and Chetan Chitnis and Sheetij Dutta and Evelina Angov and Benoit Gamain and Coppel, {Ross L.} and Beeson, {James G.} and Linda Reiling and Deepak Gaur and David Cavanagh and Ben Gyan and Nhabomba, {Augusto J.} and Campo, {Joseph J.} and Gemma Moncunill",
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month = "3",
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Dobaño, C, Santano, R, Vidal, M, Jiménez, A, Jairoce, C, Ubillos, I, Dosoo, D, Aguilar, R, Williams, NA, Díez-Padrisa, N, Ayestaran, A, Valim, C, Asante, KP, Owusu-Agyei, S, Lanar, D, Chauhan, V, Chitnis, C, Dutta, S, Angov, E, Gamain, B, Coppel, RL, Beeson, JG, Reiling, L, Gaur, D, Cavanagh, D, Gyan, B, Nhabomba, AJ, Campo, JJ & Moncunill, G 2019, 'Differential Patterns of IgG Subclass Responses to Plasmodium falciparum Antigens in Relation to Malaria Protection and RTS,S Vaccination', Frontiers in Immunology, vol. 10, 439. https://doi.org/10.3389/fimmu.2019.00439

Differential Patterns of IgG Subclass Responses to Plasmodium falciparum Antigens in Relation to Malaria Protection and RTS,S Vaccination. / Dobaño, Carlota; Santano, Rebeca; Vidal, Marta; Jiménez, Alfons; Jairoce, Chenjerai; Ubillos, Itziar; Dosoo, David; Aguilar, Ruth; Williams, Nana Aba; Díez-Padrisa, Núria; Ayestaran, Aintzane; Valim, Clarissa; Asante, Kwaku Poku; Owusu-Agyei, Seth; Lanar, David; Chauhan, Virander; Chitnis, Chetan; Dutta, Sheetij; Angov, Evelina; Gamain, Benoit; Coppel, Ross L.; Beeson, James G.; Reiling, Linda; Gaur, Deepak; Cavanagh, David; Gyan, Ben; Nhabomba, Augusto J.; Campo, Joseph J.; Moncunill, Gemma.

In: Frontiers in Immunology, Vol. 10, 439, 15.03.2019.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Differential Patterns of IgG Subclass Responses to Plasmodium falciparum Antigens in Relation to Malaria Protection and RTS,S Vaccination

AU - Dobaño, Carlota

AU - Santano, Rebeca

AU - Vidal, Marta

AU - Jiménez, Alfons

AU - Jairoce, Chenjerai

AU - Ubillos, Itziar

AU - Dosoo, David

AU - Aguilar, Ruth

AU - Williams, Nana Aba

AU - Díez-Padrisa, Núria

AU - Ayestaran, Aintzane

AU - Valim, Clarissa

AU - Asante, Kwaku Poku

AU - Owusu-Agyei, Seth

AU - Lanar, David

AU - Chauhan, Virander

AU - Chitnis, Chetan

AU - Dutta, Sheetij

AU - Angov, Evelina

AU - Gamain, Benoit

AU - Coppel, Ross L.

AU - Beeson, James G.

AU - Reiling, Linda

AU - Gaur, Deepak

AU - Cavanagh, David

AU - Gyan, Ben

AU - Nhabomba, Augusto J.

AU - Campo, Joseph J.

AU - Moncunill, Gemma

PY - 2019/3/15

Y1 - 2019/3/15

N2 - Naturally acquired immunity (NAI) to Plasmodium falciparum malaria is mainly mediated by IgG antibodies but the subclasses, epitope targets and effector functions have not been unequivocally defined. Dissecting the type and specificity of antibody responses mediating NAI is a key step toward developing more effective vaccines to control the disease. We investigated the role of IgG subclasses to malaria antigens in protection against disease and the factors that affect their levels, including vaccination with RTS,S/AS01E. We analyzed plasma and serum samples at baseline and 1 month after primary vaccination with RTS,S or comparator in African children and infants participating in a phase 3 trial in two sites of different malaria transmission intensity: Kintampo in Ghana and Manhiça in Mozambique. We used quantitative suspension array technology (qSAT) to measure IgG1-4 responses to 35 P. falciparum pre-erythrocytic and blood stage antigens. Our results show that the pattern of IgG response is predominantly IgG1 or IgG3, with lower levels of IgG2 and IgG4. Age, site and RTS,S vaccination significantly affected antibody subclass levels to different antigens and susceptibility to clinical malaria. Univariable and multivariable analysis showed associations with protection mainly for cytophilic IgG3 levels to selected antigens, followed by IgG1 levels and, unexpectedly, also with IgG4 levels, mainly to antigens that increased upon RTS,S vaccination such as MSP5 and MSP1 block 2, among others. In contrast, IgG2 was associated with malaria risk. Stratified analysis in RTS,S vaccinees pointed to novel associations of IgG4 responses with immunity mainly involving pre-erythrocytic antigens upon RTS,S vaccination. Multi-marker analysis revealed a significant contribution of IgG3 responses to malaria protection and IgG2 responses to malaria risk. We propose that the pattern of cytophilic and non-cytophilic IgG antibodies is antigen-dependent and more complex than initially thought, and that mechanisms of both types of subclasses could be involved in protection. Our data also suggests that RTS,S efficacy is significantly affected by NAI, and indicates that RTS,S vaccination significantly alters NAI.

AB - Naturally acquired immunity (NAI) to Plasmodium falciparum malaria is mainly mediated by IgG antibodies but the subclasses, epitope targets and effector functions have not been unequivocally defined. Dissecting the type and specificity of antibody responses mediating NAI is a key step toward developing more effective vaccines to control the disease. We investigated the role of IgG subclasses to malaria antigens in protection against disease and the factors that affect their levels, including vaccination with RTS,S/AS01E. We analyzed plasma and serum samples at baseline and 1 month after primary vaccination with RTS,S or comparator in African children and infants participating in a phase 3 trial in two sites of different malaria transmission intensity: Kintampo in Ghana and Manhiça in Mozambique. We used quantitative suspension array technology (qSAT) to measure IgG1-4 responses to 35 P. falciparum pre-erythrocytic and blood stage antigens. Our results show that the pattern of IgG response is predominantly IgG1 or IgG3, with lower levels of IgG2 and IgG4. Age, site and RTS,S vaccination significantly affected antibody subclass levels to different antigens and susceptibility to clinical malaria. Univariable and multivariable analysis showed associations with protection mainly for cytophilic IgG3 levels to selected antigens, followed by IgG1 levels and, unexpectedly, also with IgG4 levels, mainly to antigens that increased upon RTS,S vaccination such as MSP5 and MSP1 block 2, among others. In contrast, IgG2 was associated with malaria risk. Stratified analysis in RTS,S vaccinees pointed to novel associations of IgG4 responses with immunity mainly involving pre-erythrocytic antigens upon RTS,S vaccination. Multi-marker analysis revealed a significant contribution of IgG3 responses to malaria protection and IgG2 responses to malaria risk. We propose that the pattern of cytophilic and non-cytophilic IgG antibodies is antigen-dependent and more complex than initially thought, and that mechanisms of both types of subclasses could be involved in protection. Our data also suggests that RTS,S efficacy is significantly affected by NAI, and indicates that RTS,S vaccination significantly alters NAI.

KW - antibody

KW - children

KW - IgG subclass

KW - Malaria

KW - naturally acquired immunity

KW - Plasmodium falciparum

KW - protection

KW - vaccine

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U2 - 10.3389/fimmu.2019.00439

DO - 10.3389/fimmu.2019.00439

M3 - Article

VL - 10

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

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