Abstract
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.
Highlights
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
In this study IgG avidity against the repeat region of CSP was measured after the second and third injection of RTS,S/AS01E in infants that received the vaccine as part of a phase IIb clinical trial to assess safety and efficacy of RTS,S/AS01E in the age-group targeted by the expanded programme on immunization (EPI) [5,12]
As reported earlier [5], high anti-CSP IgG titres after three vaccine injections were associated with a reduction in subsequent incidence of clinical malaria: the hazard ratio of a ten-fold increase in anti-CSP IgG was 0.52, which corresponds to a 48% risk reduction
Summary
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. The exact mechanism of RTS,S-mediated protection is not known, Immunoglobulin G antibodies (IgG) against the CSP repeat region are likely to play an important role since the concentration of anti-CSP IgG partly explains protection in most studies that assessed efficacy of RTS,S in African children [4,5,6]. In this study IgG avidity against the repeat region of CSP was measured after the second and third injection of RTS,S/AS01E in infants that received the vaccine as part of a phase IIb clinical trial to assess safety and efficacy of RTS,S/AS01E in the age-group targeted by the expanded programme on immunization (EPI) [5,12]
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