Safety, tolerability, and Plasmodium falciparum transmission-reducing activity of monoclonal antibody TB31F: a single-centre, open-label, first-in-human, dose-escalation, phase 1 trial in healthy malaria-naive adults

Combatting seasonal malaria transmission using a highly potent Plasmodium falciparum transmission-blocking monoclonal antibody

“…TB31F targets Pfs48/45, which has limited genetic variation, a shared advantage of many transmission-blocking vaccine candidates (11). The potency of TB31F has been demonstrated against two genetically distant parasite lines (15); the original rat mAb 85RF45.1 that formed the basis for TB31F has been tested against genetically diverse gametocyte isolates from Cameroon and Burkina Faso, further demonstrating universal activity and no indications for escape mutants (47).…”

“…Overview of the pharmaco-epidemiological modelling workflow. (A) We used data from the first-in-human trial of TB31F (15) for pharmacokinetic-pharmacodynamic modelling. (B) The final pharmacokinetic model consisted of three disposition compartments and an absorption compartment for subcutaneously administered doses.…”

“…We used data from a first-in-human, dose escalation study of TB31F that was performed in 25 healthy adult malaria naïve volunteers (15). There were five study arms (n=5 per arm) with escalating TB31F dose: four groups received intravenous TB31F at 0.1 mg/kg, 1 mg/kg, 3 mg/kg and 10 mg/kg; a fifth group received 100 mg TB31F subcutaneously.…”

“…This level of TRA, historically used as threshold for potency of transmission-blocking vaccines (30), was used for dose selection. Given available data on the safety and efficacy of intravenous administration (15), we used this route of administration for our further analyses. We extrapolated the pharmacokinetic model to children and explored weight-based dosing, aiming to reach an equivalent duration >80% TRA in children as observed with 10 mg/kg in adults.…”

“…It targets a highly conserved epitope on Pfs48/45, which is expressed on Plasmodium falciparum mature gametocytes and gametes. In a recent first-in-human study, a single intravenous dose up to 10 mg/kg was well-tolerated in adult study participants with minimal to no side-effects (15). In the highest dose group, serum from trial participants fully prevented transmission to mosquitoes in ex-vivo assays throughout 84 days of follow-up.…”