Steinhardt LC, Richie TL, Yego R, et al. - Given the reports of safety, tolerablilty, and feasibility of direct venous inoculation (DVI) with Plasmodium falciparum sporozoite (PfSPZ) vaccine for malaria prevention in adults, researchers sought to gain safety data for children and infants via performing an age de-escalation, dose-escalation randomized controlled trial in Siaya County, western Kenya. They enrolled children and infants (aged 5–9 years, 13–59 months, and 5–12 months) into 13 age-dose cohorts of 12 participants and randomized them to vaccine or normal saline placebo in escalating doses: 1.35 × 10⁵, 2.7 × 10⁵, 4.5 × 10⁵, 9.0 × 10⁵, and 1.8 × 10⁶ PfSPZ, with the 2 highest doses given twice, 8 weeks apart. Vaccinees and controls had similar rates of AEs for solicited (35.7% vs 41.5%) and unsolicited (83.9% vs 92.5%) AEs, respectively. Based on outcomes, infants and children could be administered PfSPZ vaccine in doses as high as 1.8 × 10⁶ by DVI, as it was safe, well tolerated, and immunogenic.