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

Research

Nahya Salim¹  Maxmilliam Mpina¹  Grace Mwangoka¹  Salim Abdulla¹  Marcel Tanner²  Selidji Todagbe Agnandji³  Anthony Ajua⁴  Benjamin Mordmüller⁵  Bertrand Lell⁵  Peter G Kremsner⁵  Marc Lievens⁶  Erik Jongert⁶  Pierre Cambron⁶  Johan Vekemans⁶  Kwaku Poku Asante⁷  Seth Owusu-Agyei⁸  Chris F Ockenhouse⁹ 

[1] Bagamoyo Research and Training Centre of Ifakara Health Institute, PO Box 78373, Bagamoyo, 360 Kiko Avenue, Mikocheni, Dar es Salaam, Tanzania;Bagamoyo Research and Training Centre of Ifakara Health Institute, PO Box 78373, Bagamoyo, 360 Kiko Avenue, Mikocheni, Dar es Salaam, Tanzania;Swiss Tropical and Public Health Institute, Basel, Switzerland;Centre de Recherches Médicales de Lambaréné (CERMEL), BP118, Lambaréné, Gabon;Eberhard Karls Universität Tübingen, Institut für Tropenmedizin, Wilhelmstraße 27, 72074, Tübingen, Germany;Eberhard Karls Universität Tübingen, Institut für Tropenmedizin, Wilhelmstraße 27, 72074, Tübingen, Germany;Centre de Recherches Médicales de Lambaréné (CERMEL), BP118, Lambaréné, Gabon;GlaxoSmithKline Biologicals, Rixensart, Belgium;Kintampo Health Research Centre, PO Box 200, Kintampo, Ghana;Kintampo Health Research Centre, PO Box 200, Kintampo, Ghana;Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, WC1E 7HT, London, UK;PATH Malaria Vaccine Initiative, 455 Massachusetts Avenue NW, Suite 1000, 20001, Washington, DC, USA;

关键词: Malaria;    RTS,S;    Vaccine;    Plasmodium falciparum;    Antibody;    Avidity;    Correlate of protection;   

DOI  :  10.1186/s12936-015-0605-7

 received in 2014-10-09, accepted in 2015-02-02,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsQuantity 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.ResultsAfter 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).ConclusionsChange in IgG response between vaccine doses merits further evaluation as a surrogate marker for RTS,S efficacy.Trial registrationClinicalTrials.gov Identifier NCT00436007.

【 授权许可】

Unknown   
© Ajua et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.