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The antimalarial monoclonal antibody TB31F was found to be highly potent in preventing the transmission of Plasmodium falciparum parasites from humans to mosquitoes. These findings were published in The Lancet Infectious Diseases.
To evaluate the efficacy of the humanized monoclonal antibody TB31F in preventing the transmission of P falciparum parasites, researchers conducted a single-center, open-label, dose-escalation, phase 1 trial in the Netherlands between 2020 and 2021. All included participants (N=25) were healthy adults with no history of malaria. Participants first received 1000 mg of oral acetaminophen and 2 mg of intravenous (IV) clemastine and were then assigned to receive either 0.1 (n=5; group 1), 1.0 (n=5; group 2), 3.0 (n=5; group 3), or 10.0 (n=5; group 4) mg/kg of IV TB31F, or 100 mg of subcutaneous TB31F (n=5; group 5). The primary outcomes were the rate and severity of adverse events, as well as the occurrence of clinically significant laboratory abnormalities; secondary outcomes were the pharmacokinetics and functional transmission-reducing activity (TRA) of TB31F.
Among participants included in the analysis, 52% were women, the mean age was 23.5 (range, 19.0-34.0) years, and the mean BMI was 24.1 (range, 19.5-29.5) kg/m2.
After the administration of TB31F, fatigue was reported by participants in groups 1 (100%), 2 (40%), 3 (20%), 4 (60%), and 5 (40%); headache by groups 1 (20%), 2 (20%), and 4 (60%); injection site pain by groups 3 (20%) and 5 (80%); injection site erythema by group 2 (20%); fever by group 4 (20%); and myalgia by group 1 (20%). All reported adverse events were of mild to moderate severity. In addition, no clinically significant abnormalities were noted in laboratory analyses.
The researchers found that TB31F had dose-dependent peak concentrations and dose-independent terminal half-life patterns. Among participants in groups 1, 2, 3, and 4 who received IV TB31F, the geometric mean maximum plasma concentration (Cmax) was 2.94, 28.3, 80.8, and 255 µg/mL. Of participants who received subcutaneous TB31F (group 5), the geometric mean Cmax was 9.28 µg/mL at day 4.3, with a bioavailability of 52%. Overall, the estimated terminal half-life was 32.2 days.
Among all participants, TB31F was detectable in serum through day 84, with the exception of 1 participant in group 5.
A standard membrane feeding assay was used to determine the TRA of TB31F following administration. Results showed that a TRA of more than 80% against the West African P falciparum strain NF54 was observed for 28 days or more among participants in group 2, for 56 days or more among those in group 3, and for 84 days or more among those in group 4. Of the 5 participants who received subcutaneous TB31F (group 5), a TRA of more than 80% for a duration of 28 days or more was observed in 4.
After further analysis, the serum concentration of TB31F required to achieve a TRA of 80% was found to be 2.1 µg/mL. Owing to this finding, the researchers estimated that a single injection of TB31F at a dose of 10 mg/kg was sufficient to protect against malaria transmission, resulting in a TRA of 80% or more for 160 days.
Limitations include potential human error in regard to the preparation and administration of TB31F, as well as the inclusion of only healthy adults with no history malaria.
According to the researchers, “[these] findings support further development of TB31F as a promising cointervention tool to be studied in malaria-endemic populations…”
Reference
van der Boor SC, Smit MJ, van Beek SW, et al. 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. Lancet Infect Dis. 2022;S1473-3099(22)00428-5. doi:10.1016/S1473-3099(22)00428-5
