Last Updated: 17/02/2023
Characterizing the longitudinal immune response to salivary antigens of Southeast Asian mosquito vectors of malaria, with a human challenge model
Objectives
To conduct a world-first controlled human biting challenge trial, in which volunteers are repeatedly bitten by predetermined numbers of three malaria vectors dominant in the GMS to help inform if this salivary antibody approach can be used as a marker of vector exposure in the Asia Pacific, and if this approach can be used to track changes in exposure over time.
Burnet Institute, Australia
University of Melbourne (UoM), Australia
Having sensitive and accurate tools to monitor changes in malaria transmission risk is important for achieving the goal of malaria elimination in the Asia Pacific. Conventional methods involve collecting mosquitoes at specific sites and dissecting them for detection of Plasmodium parasites. The logistical constraints of such collections, in addition to reduced sensitivity in low transmission areas, has seen the WHO call for innovative tools to measure malaria transmission risk and increase vector surveillance capacity. Humans mount an immune response to proteins in mosquito saliva (injected into the human as it feeds). Measurement of antibodies against these salivary proteins has the potential to serve as a proxy measure of levels of exposure to bites of malaria vectors at an individual- and population-level. Numerous African studies have explored using antibodies against the An. gambiae (the dominant African vector) Salivary Gland 6 (gSG6) protein as markers for transmission. However, as the SG6 gene shares only moderate (<~50%) sequence homology with other Anopheles, evidence for the appropriateness of this approach to surveil the wide vector diversity (>20 Anopheles species) in the Asia Pacific is limited. Furthermore, its ability to track changes in transmission over time is unknown, as the rate of SG6 antibody boosting and decay is yet to be quantified.
Participants were allocated using a block-randomised design to receive either a low (total 35) or high (total 305) dose of bites from An. minimus, An. maculatus or An. dirus, which are the dominant vectors of the GMS. Blood samples were collected weekly over a 16-week follow-up period, including two baseline visits prior to mosquito challenge, nine visits where participants were concurrently exposed to mosquito biting, and eight post-exposure follow-ups. A total of 77 participants were enrolled. While 15 participants have complete sampling (19 visits), many participants were unable to complete the sampling program due to COVID-19, with 11 participants having ≥17 visits (6-weeks post biting exposure), 10 having 15 visits (4-weeks post biting exposure), and 52 with 11 visits (complete biting exposure).
Nov 2021 — Oct 2023
$15,000
