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http://hdl.handle.net/2445/121174
Title: | Identifying Immune Correlates of Protection Against Plasmodium falciparum Through a Novel Approach to Account for Heterogeneity in Malaria Exposure |
Author: | Valmaseda, Aida Macete, Eusebio Víctor Nhabomba, Augusto J. Guinovart, Caterina Aide, Pedro Carlos Paulino Bardají, Azucena Bassat Orellana, Quique Nhampossa, Tacilta Maculuve, Sónia Amós Casellas, Aina Quintó, Llorenç Sanz, Sergi Jiménez, Alfons Feng, Gaoqian Langer, Christine Reiling, Linda Reddy, K. Sony Pandey, Alok Kumar Chitnis, Chetan E. Chauhan, Virander Singh Aguilar, Ruth Aponte, John J. Dobaño, Carlota, 1969- Beeson, James G. Gaur, Deepak Menéndez, Clara Alonso, Pedro Mayor Aparicio, Alfredo Gabriel |
Keywords: | Plasmodium falciparum Vacunes Plasmodium falciparum Vaccines |
Issue Date: | 18-Sep-2017 |
Publisher: | Oxford University Press |
Abstract: | Background: A main criterion to identify malaria vaccine candidates is the proof that acquired immunity against them is associated with protection from disease. The age of the studied individuals, heterogeneous malaria exposure, and assumption of the maintenance of a baseline immune response can confound these associations. Methods: Immunoglobulin G/immunoglobulin M (IgG/ IgM) levels were measured by Luminex(R) in Mozambican children monitored for clinical malaria from birth until 3 years of age, together with functional antibodies. Studied candidates were pre-erythrocytic and erythrocytic antigens, including EBAs/PfRhs, MSPs, DBLs, and novel antigens merely or not previously studied in malaria-exposed populations. Cox regression models were estimated at 9 and 24 months of age, accounting for heterogeneous malaria exposure or limiting follow-up according to the antibody's decay. Results: Associations of antibody responses with higher clinical malaria risk were avoided when accounting for heterogeneous malaria exposure or when limiting the follow-up time in the analyses. Associations with reduced risk of clinical malaria were found only at 24 months old, but not younger children, for IgG breadth and levels of IgG targeting EBA140III-V, CyRPA, DBL5epsilon and DBL3x, together with C1q-fixation activity by antibodies targeting MSP119. Conclusions: Malaria protection correlates were identified, only in children aged 24 months old when accounting for heterogeneous malaria exposure. These results highlight the relevance of considering age and malaria exposure, as well as the importance of not assuming the maintenance of a baseline immune response throughout the follow-up. Results may be misleading if these factors are not considered. |
Note: | Versió postprint del document publicat a: http://dx.doi.org/10.1093/cid/cix837 |
It is part of: | Clinical Infectious Diseases, 2018, vol. 66, num. 4, p. 586-593 |
URI: | http://hdl.handle.net/2445/121174 |
Related resource: | http://dx.doi.org/10.1093/cid/cix837 |
ISSN: | 1058-4838 |
Appears in Collections: | Articles publicats en revistes (ISGlobal) |
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valmaseda2018_2905.pdf | 199.39 kB | Adobe PDF | View/Open |
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