Avidity of anti-circumsporozoite antibodies following vaccination with RTS,S/AS01E in young children

The nature of protective immune responses elicited by immunization with the candidate malaria vaccine RTS,S is still incompletely understood. Antibody levels correlate with protection against malaria infection, but considerable variation in outcome is unexplained (e.g., children may experience malar...

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Bibliographic Details
Published in:PloS one 2014, Vol.9 (12), p.e115126-e115126
Main Authors: Olotu, Ally, Clement, Frederic, Jongert, Erik, Vekemans, Johan, Njuguna, Patricia, Ndungu, Francis M, Marsh, Kevin, Leroux-Roels, Geert, Bejon, Philip
Format: Article
Language:English
Subjects:
Antibodies
Antibodies, Protozoan - blood
Antibodies, Protozoan - immunology
Antibody Affinity
Avidity
Biology and Life Sciences
Case-Control Studies
Children
Circumsporozoite protein
Elution
Enzyme-linked immunosorbent assay
Erythrocytes
Exposure
Health risks
Humans
Immune response
Immunization
Immunoglobulins
Infant
Kenya
Malaria
Malaria Vaccines - immunology
Malaria, Falciparum - epidemiology
Malaria, Falciparum - immunology
Malaria, Falciparum - prevention & control
Measurement methods
Medicin och hälsovetenskap
Medicine and Health Sciences
Parasites
Protozoan Proteins - immunology
Risk
Studies
Subgroups
Vaccination
Vaccines
Variance analysis
Vector-borne diseases
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Summary:The nature of protective immune responses elicited by immunization with the candidate malaria vaccine RTS,S is still incompletely understood. Antibody levels correlate with protection against malaria infection, but considerable variation in outcome is unexplained (e.g., children may experience malaria despite high anti-circumsporozoite [CS] titers). We measured the avidity index (AI) of the anti-CS antibodies raised in subgroup of 5-17 month old children in Kenya who were vaccinated with three doses of RTS,S/AS01E between March and August 2007. We evaluated the association between the AI and the subsequent risk of clinical malaria. We selected 19 cases (i.e., with clinical malaria) and 42 controls (i.e., without clinical malaria), matching for anti-CS antibody levels and malaria exposure. We assessed their sera collected 1 month after the third dose of the vaccine, in March 2008 (range 4-10 months after the third vaccine), and at 12 months after the third vaccine dose. The mean AI was 45.2 (95% CI: 42.4 to 48.1), 45.3 (95% CI: 41.4 to 49.1) and 46.2 (95% CI; 43.2 to 49.3) at 1 month, in March 2008 (4-10 months), and at 12 months after the third vaccination, respectively (p = 0.9 by ANOVA test for variation over time). The AI was not associated with protection from clinical malaria (OR = 0.90; 95% CI: 0.49 to 1.66; p = 0.74). The AI was higher in children with high malaria exposure, as measured using the weighted local prevalence of malaria, compared to those with low malaria exposure at 1 month post dose 3 (p = 0.035). Our data suggest that in RTS,S/AS01E-vaccinated children residing in malaria endemic countries, the avidity of anti-circumsporozoite antibodies, as measured using an elution ELISA method, was not associated with protection from clinical malaria. Prior natural malaria exposure might have primed the response to RTS,S/AS01E vaccination.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0115126