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The effect of immunization schedule with the malaria vaccine candidate RTS,S/AS01E on protective efficacy and anti-circumsporozoite protein antibody avidity in African infants

Ajua, Anthony and Lell, Bertrand and Agnandji, Selidji Todagbe and Asante, Kwaku Poku and Owusu-Agyei, Seth and Mwangoka, Grace and Mpina, Maxmilliam and Salim, Nahya and Tanner, Marcel and Abdulla, Salim and Vekemans, Johan and Jongert, Erik and Lievens, Marc and Cambron, Pierre and Ockenhouse, Chris F. and Kremsner, Peter G. and Mordmüller, Benjamin. (2015) The effect of immunization schedule with the malaria vaccine candidate RTS,S/AS01E on protective efficacy and anti-circumsporozoite protein antibody avidity in African infants. Malaria journal, Vol. 14 , 72.

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Abstract

The malaria vaccine RTS,S induces antibodies against the Plasmodium falciparum circumsporozoite protein (CSP) and the concentration of Immunoglobulin G (IgG) against the repeat region of CSP following vaccination is associated with protection from P. falciparum malaria. So far, only the quantity of anti-CSP IgG has been measured and used to predict vaccination success, although quality (measured as avidity) of the antigen-antibody interaction shall be important since only a few sporozoites circulate for a short time after an infectious mosquito bite, likely requiring fast and strong binding.; Quantity and avidity of anti-CSP IgG in African infants who received RTS,S/AS01E in a 0-1-2-month or a 0-1-7-month schedule in a phase 2 clinical trial were measured by enzyme-linked immunosorbent assay. Antibody avidity was defined as the proportion of IgG able to bind in the presence of a chaotropic agent (avidity index). The effect of CSP-specific IgG concentration and avidity on protective efficacy was modelled using Cox proportional hazards.; After the third dose, quantity and avidity were similar between the two vaccination schedules. IgG avidity after the last vaccine injection was not associated with protection, whereas the change in avidity following second and third RTS,S/AS01E injection was associated with a 54% risk reduction of getting malaria (hazard ratio: 0.46; 95% confidence interval (CI): 0.22-0.99) in those participants with a change in avidity above the median. The change in anti-CSP IgG concentration following second and third injection was associated with a 77% risk reduction of getting malaria (hazard ratio: 0.23, 95% CI: 0.11-0.51).; Change in IgG response between vaccine doses merits further evaluation as a surrogate marker for RTS,S efficacy.; ClinicalTrials.gov Identifier NCT00436007.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin > Malaria Vaccines (Tanner)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Former Units within Swiss TPH > Malaria Vaccines (Tanner)
UniBasel Contributors:Tanner, Marcel
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:BioMed Central
ISSN:1475-2875
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:31 Dec 2015 10:58
Deposited On:03 Jul 2015 08:53

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