Differential Patterns of IgG Subclass Responses to Plasmodium falciparum Antigens in Relation to Malaria Protection and RTS,S Vaccination
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 develop...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.00439/full |
| _version_ | 1819315475395379200 |
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| author | Carlota Dobaño Carlota Dobaño Rebeca Santano Marta Vidal Alfons Jiménez Alfons Jiménez Chenjerai Jairoce Itziar Ubillos David Dosoo Ruth Aguilar Nana Aba Williams Núria Díez-Padrisa Aintzane Ayestaran Clarissa Valim Clarissa Valim Kwaku Poku Asante Seth Owusu-Agyei Seth Owusu-Agyei David Lanar Virander Chauhan Chetan Chitnis Sheetij Dutta Evelina Angov Benoit Gamain Ross L. Coppel James G. Beeson Linda Reiling Deepak Gaur Deepak Gaur David Cavanagh Ben Gyan Ben Gyan Augusto J. Nhabomba Joseph J. Campo Joseph J. Campo Gemma Moncunill Gemma Moncunill |
| author_facet | Carlota Dobaño Carlota Dobaño Rebeca Santano Marta Vidal Alfons Jiménez Alfons Jiménez Chenjerai Jairoce Itziar Ubillos David Dosoo Ruth Aguilar Nana Aba Williams Núria Díez-Padrisa Aintzane Ayestaran Clarissa Valim Clarissa Valim Kwaku Poku Asante Seth Owusu-Agyei Seth Owusu-Agyei David Lanar Virander Chauhan Chetan Chitnis Sheetij Dutta Evelina Angov Benoit Gamain Ross L. Coppel James G. Beeson Linda Reiling Deepak Gaur Deepak Gaur David Cavanagh Ben Gyan Ben Gyan Augusto J. Nhabomba Joseph J. Campo Joseph J. Campo Gemma Moncunill Gemma Moncunill |
| author_sort | Carlota Dobaño |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-24T10:00:42Z |
| format | Article |
| id | doaj.art-32aa5029682c4bfd9b0f38f363686bb5 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-24T10:00:42Z |
| publishDate | 2019-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-32aa5029682c4bfd9b0f38f363686bb52022-12-21T17:01:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-03-011010.3389/fimmu.2019.00439433511Differential Patterns of IgG Subclass Responses to Plasmodium falciparum Antigens in Relation to Malaria Protection and RTS,S VaccinationCarlota Dobaño0Carlota Dobaño1Rebeca Santano2Marta Vidal3Alfons Jiménez4Alfons Jiménez5Chenjerai Jairoce6Itziar Ubillos7David Dosoo8Ruth Aguilar9Nana Aba Williams10Núria Díez-Padrisa11Aintzane Ayestaran12Clarissa Valim13Clarissa Valim14Kwaku Poku Asante15Seth Owusu-Agyei16Seth Owusu-Agyei17David Lanar18Virander Chauhan19Chetan Chitnis20Sheetij Dutta21Evelina Angov22Benoit Gamain23Ross L. Coppel24James G. Beeson25Linda Reiling26Deepak Gaur27Deepak Gaur28David Cavanagh29Ben Gyan30Ben Gyan31Augusto J. Nhabomba32Joseph J. Campo33Joseph J. Campo34Gemma Moncunill35Gemma Moncunill36ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, SpainCentro de Investigação em Saúde de Manhiça (CISM), Manhiça, MozambiqueISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, SpainISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, SpainISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, SpainSpanish Consortium for Research in Epidemiology and Public Health (CIBERESP), Barcelona, SpainCentro de Investigação em Saúde de Manhiça (CISM), Manhiça, MozambiqueISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, SpainKintampo Health Research Centre, Kintampo, GhanaISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, SpainISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, SpainISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, SpainISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, SpainDepartment of Osteopathic Medical Specialties, Michigan State University, East Lansing, MI, United StatesDepartment of Immunology and Infectious Diseases, Harvard T.H. Chen School of Public Health, Boston, MA, United StatesKintampo Health Research Centre, Kintampo, GhanaKintampo Health Research Centre, Kintampo, GhanaDisease Control Department, London School of Hygiene and Tropical Medicine, London, United KingdomMalaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, MD, United StatesMalaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, IndiaMalaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, IndiaMalaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, MD, United StatesMalaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, MD, United States0Unité Biologie Intégrée du Globule Rouge, Laboratoire d'Excellence GR-Ex, UMR_S1134, Inserm, INTS, Université Sorbonne Paris Cité, Université Paris Diderot, Paris, France1Infection and Immunity Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Melbourne, VIC, Australia2Burnet Institute, Melbourne, VIC, Australia2Burnet Institute, Melbourne, VIC, AustraliaMalaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India3Laboratory of Malaria and Vaccine Research, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India4Ashworth Laboratories, Centre for Immunity, Infection and Evolution, School of Biological Sciences, Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United KingdomKintampo Health Research Centre, Kintampo, Ghana5Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, GhanaCentro de Investigação em Saúde de Manhiça (CISM), Manhiça, MozambiqueISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, SpainCentro de Investigação em Saúde de Manhiça (CISM), Manhiça, MozambiqueISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, SpainCentro de Investigação em Saúde de Manhiça (CISM), Manhiça, MozambiqueNaturally 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.00439/fullMalariaPlasmodium falciparumantibodyIgG subclassnaturally acquired immunityprotection |
| spellingShingle | Carlota Dobaño Carlota Dobaño Rebeca Santano Marta Vidal Alfons Jiménez Alfons Jiménez Chenjerai Jairoce Itziar Ubillos David Dosoo Ruth Aguilar Nana Aba Williams Núria Díez-Padrisa Aintzane Ayestaran Clarissa Valim Clarissa Valim Kwaku Poku Asante Seth Owusu-Agyei Seth Owusu-Agyei David Lanar Virander Chauhan Chetan Chitnis Sheetij Dutta Evelina Angov Benoit Gamain Ross L. Coppel James G. Beeson Linda Reiling Deepak Gaur Deepak Gaur David Cavanagh Ben Gyan Ben Gyan Augusto J. Nhabomba Joseph J. Campo Joseph J. Campo Gemma Moncunill Gemma Moncunill Differential Patterns of IgG Subclass Responses to Plasmodium falciparum Antigens in Relation to Malaria Protection and RTS,S Vaccination Frontiers in Immunology Malaria Plasmodium falciparum antibody IgG subclass naturally acquired immunity protection |
| title | Differential Patterns of IgG Subclass Responses to Plasmodium falciparum Antigens in Relation to Malaria Protection and RTS,S Vaccination |
| title_full | Differential Patterns of IgG Subclass Responses to Plasmodium falciparum Antigens in Relation to Malaria Protection and RTS,S Vaccination |
| title_fullStr | Differential Patterns of IgG Subclass Responses to Plasmodium falciparum Antigens in Relation to Malaria Protection and RTS,S Vaccination |
| title_full_unstemmed | Differential Patterns of IgG Subclass Responses to Plasmodium falciparum Antigens in Relation to Malaria Protection and RTS,S Vaccination |
| title_short | Differential Patterns of IgG Subclass Responses to Plasmodium falciparum Antigens in Relation to Malaria Protection and RTS,S Vaccination |
| title_sort | differential patterns of igg subclass responses to plasmodium falciparum antigens in relation to malaria protection and rts s vaccination |
| topic | Malaria Plasmodium falciparum antibody IgG subclass naturally acquired immunity protection |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.00439/full |
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