GavaghanCommunications | Snippets of science by GC by GC||Issue 10: 13.10 - 19.10.10.

Item 1:P.falciparum, preerythrocyte antigens, vaccine efficacy statistical model.

Mathematical model that predicts efficacy of 0.75 for a vaccine working in combination against two hepatic merozoite antigens also gives tool for discussing biology of other P. falciparum's antigens during the parasite's life cycle using antibody titre field data from 2001 and observations from the literature.

Michael T. White at al created comparatively simple probability models to reanalyse relationships in data collected in 2001 from 68 Kenyans living in an area where Malaria is endemic but where the population has a degree of natural immunity. The models also predict theoretical vaccine efficacies of 0.75 for a combined vaccine against preerythrocytic antigens circumsporozoite protein and thrombospondin-related adhesive protein.

Immunogenic interference between the two IgG antibodies would need to be overcome in such a vaccine, and how marked the actual efficacy would be would depend on the natural immunity background against which the vaccine's boost to immunity was evaluated.

The authors reference work on TRAP (thrombospondin-related adhesive protein), writing "...there is some evidence to suggest that TRAP antibodies do not inhibit sporozoite infectivity in vivo.

The model reported by the Proceedings of the Royal Society Biology focuses on sporozoites and assumes that the biology of the situation is that each natural preerythrocytic antibody and cell-mediated response is independent one of the other and also that each sporozoite acts independently.

Value ranges for the models' parameters reported October 2010 were determined by fitting model predictions to observed times to reinfection taken from the 2001 study published in the American Journal of Tropical Medicine and Hygiene in 2005. Models of the immune response as a whole compared with an immune response for preerythrocytic antigens alone gave a less close fit with the observed data.

That data, from the 2001 field study, comprised blood samples taken each week for 14 weeks from each participant after treatment to clear parasitaemia. Data ceased to be included in the study if an individual did not turn up for two consecutive weeks, but was included up to that point. Six different immunoglobulin G antibody titres (titre in this context means how much antibody is in the blood) to six different antigens of P. falciparum at different stages in its life cycle and in its parasitic relationship with humans were analysed by Michael T. White et al.

Two types of dose response curve for IgG (convex and threshold) were modeled in this theoretical reanalysis to identify the likelihood of a sporozoite evading the immunoglobulin G response, and the models do not take account of probabilities subsequent to the end of data collected from an individual but within the 14 week data collection period nor probabilities consequential to reasons for ceasing.

The researchers assert, "For an infectious bite to progress to blood-stage malaria, just one sporozoite must evade the pre-erythrocytic immune response."

The researchers draw attention to phase II and III malaria vaccine clinical trials. RTS,S/AS correction "o" in the first edition ought to have been "O"1, ie RTS,S/ASo1 is the closest to possible licensing, and Michael T White et al report that their data support the view of the phase II RTS,S trial data that sporozoite vaccine efficacy rests on boosting the CSP antibody titre.

The above named vaccination on trial ought to be designated with all capitalised letters, as it appears in the journal on which this item is based. If this had become the paying, searchable database it is my intent to create this correction would already have been circulated by email.

Based on a paper in The Proceedings of the Royal SocietyB: Efficacy for antibody-mediated preerythrocyte malaria vaccines by Michael White et al.DOI:10.1098/rspb.2010.1697.

The following text is still useful reference reading for both current information and as a text against which to evaluate bibliographic references in the current literature.:
Encyclopaedia of Molecular Biology, Blackwell, 1994, Ed-in-chief Sir John Kendrew.


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