Epitope-specific competitive ELISA predicts malaria transmission-blocking vaccine Pfs230D1 activity measured in standard membrane feeding assay

TL;DR

A new ELISA test predicts how well a malaria vaccine candidate prevents mosquito infections, potentially replacing a more complex assay.

Contribution

An epitope-specific competitive ELISA platform (P230Compete) is developed to predict vaccine activity against malaria transmission.

Findings

EUF and IgG1F strongly correlate and predict TRA with high accuracy.

Combining EUF and IgG1F improves predictive performance for TRA.

P230Compete shows promise as a scalable alternative to SMFA for vaccine trials.

Abstract

Functional antibody responses to malaria transmission-blocking vaccines (TBVs) are assessed using the standard membrane feeding assay (SMFA). This assay quantifies the percentage reduction of oocyst levels in mosquitoes fed gametocytes mixed with antisera/antibodies, referred to as transmission-reducing activity (TRA). As TBVs advance to large clinical trials, new scalable assays are needed to characterize vaccine responses. Here, we developed an epitope-specific competitive ELISA platform (P230Compete) for TBV candidate Pfs230D1, based on single-chain variable fragments against epitopes recognized by human monoclonal antibodies with high TRA. We quantified functional epitope-specific antibody responses (F) in phase I Pfs230D1-EPA/AS01 vaccine trial participants, using 171 serum samples collected at 2 postvaccination time points. Five antibody features were examined by P230Compete, including total IgG (reported as ELISA units, EUF), IgG subclasses (IgG1F, IgG3F, IgG4F), and bound complement factor C1q (C1qF). EUF and IgG1F demonstrated strong correlation and excellent prediction of TRA (≥80%) in logistic regression analysis (AUC of 0.81 for both assays after dose 3, and 0.80 and 0.76 after dose 4). Furthermore, combining EUF and IgG1F showed even better predictive performance at each time point. P230Compete offers a promising proxy assay to replace SMFA in late-stage Pfs230D1 trials.

A novel epitope-specific competitive ELISA for leading malaria transmission-blocking vaccine Pfs230D1 predicts serum activity to reduce mosquito infections measured in standard membrane feeding assays.

Figures