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Title: Differential Patterns of IgG Subclass Responses to Plasmodium falciparum Antigens in Relation to Malaria Protection and RTS,S Vaccination
Author: Dobaño, Carlota, 1969-
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
Keywords: Malària
Plasmodium falciparum
Issue Date: 15-Mar-2019
Publisher: Frontiers Research Foundation
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.
Note: Reproducció del document publicat a:
It is part of: Frontiers in Immunology, 2019, vol. 10
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ISSN: 1664-3224
Appears in Collections:Articles publicats en revistes (ISGlobal)

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