Efficacy model for antibody-mediated pre-erythrocytic malaria vaccines

Abstract

Antibodies to the pre-erythrocytic antigens, circumsporozoite protein (CSP), thrombospondin-related adhesive protein (TRAP) and liver-stage antigen 1, have been measured in field studies of semiimmune adults and shown to correlate with protection from Plasmodium falciparum infection. A mathematical model is formulated to estimate the probability of sporozoite infection as a function of antibody titres to multiple pre-erythrocytic antigens. The variation in antibody titres from field data was used to estimate the relationship between the probability of P. falciparum infection per infectious mosquito bite and antibody titre. Using this relationship, we predict the effect of vaccinations that boost baseline CSP or TRAP antibody titres. Assuming the estimated relationship applies to vaccineinduced antibody titres, then single-component CSP or TRAP antibody-mediated pre-erythrocytic vaccines are likely to provide partial protection from infection, with vaccine efficacy of approximately 50 per cent depending on the magnitude of the vaccine-induced boost to antibody titres. It is possible that the addition of a TRAP component to a CSP-based vaccine such as RTS,S would provide an increase in infection-blocking efficacy of approximately 25 per cent should the problem of immunological interference between antigens be overcome.

Adjuvant-like Effect of Vaccinia Virus 14K Protein: A Case Study with Malaria Vaccine Based on the Circumsporozoite Protein

“…Protective immunity against malaria associates with circulating IgG Abs against CS (47). Previous studies have also shown the ability of fusion proteins to induce strong humoral responses based on their ability to form large molecular mass aggregates (20).…”

A combined analysis of immunogenicity, antibody kinetics and vaccine efficacy from phase 2 trials of the RTS,S malaria vaccine

“…We used the model-predicted anti-CSP antibody titres over time to estimate a dose–response curve for the relationship between antibody levels and protection from infection and disease using survival analysis methods [[21],[22]]. Vaccine efficacy against infection V ( t ) is estimated from antibody titre CSP ( t ) according to the following dose–response curve:$\mathit{V}\left(\mathrm{italict}\right)={\mathrm{italicV}}_{\text{max}}\left(1-\frac{1}{1+{\left(\frac{\mathrm{italicCSP}\left(\mathit{t}\right)}{\mathit{\beta }}\right)}^{\mathrm{italic\alpha }}}\right)$where α and β are shape parameters to be estimated, and V max is the maximum efficacy against infection [[21]].…”

Virus-Like Particle (VLP) Plus Microcrystalline Tyrosine (MCT) Adjuvants Enhance Vaccine Efficacy Improving T and B Cell Immunogenicity and Protection against Plasmodium berghei/vivax

“…TRAP has been reported to be a target for T cell-based vaccines, but some studies have also shown the importance of antibodies against TRAP as protective effector molecules against malaria [9,10,11]. …”