The radiation-attenuated Plasmodium falciparum sporozoite (PfSPZ) vaccine 
provides protection against P. falciparum infection in malaria-naïve adults. 
Preclinical studies show that T cell-mediated immunity is required for 
protection and is readily induced in humans after vaccination. However, previous 
malaria exposure can limit immune responses and vaccine efficacy (VE) in adults. 
We hypothesized that infants with less previous exposure to malaria would have 
improved immunity and protection. We conducted a multi-arm, randomized, 
double-blind, placebo-controlled trial in 336 infants aged 5-12 months to 
determine the safety, tolerability, immunogenicity and efficacy of the PfSPZ 
Vaccine in infants in a high-transmission malaria setting in western Kenya ( 
NCT02687373 ). Groups of 84 infants each received 4.5 × 105, 9.0 × 105 or 
1.8 × 106 PfSPZ Vaccine or saline three times at 8-week intervals. The vaccine 
was well tolerated; 52 (20.6%) children in the vaccine groups and 20 (23.8%) in 
the placebo group experienced related solicited adverse events (AEs) within 28 d 
postvaccination and most were mild. There was 1 grade 3-related solicited AE in 
the vaccine group (0.4%) and 2 in the placebo group (2.4%). Seizures were more 
common in the highest-dose group (14.3%) compared to 6.0% of controls, with most 
being attributed to malaria. There was no significant protection against P. 
falciparum infection in any dose group at 6 months (VE in the 9.0 × 105 dose 
group = -6.5%, P = 0.598, the primary statistical end point of the study). VE 
against clinical malaria 3 months after the last dose in the highest-dose group 
was 45.8% (P = 0.027), an exploratory end point. There was a dose-dependent 
increase in antibody responses that correlated with VE at 6 months in the 
lowest- and highest-dose groups. T cell responses were undetectable across all 
dose groups. Detection of Vδ2+Vγ9+ T cells, which have been correlated with 
induction of PfSPZ Vaccine T cell immunity and protection in adults, were 
infrequent. These data suggest that PfSPZ Vaccine-induced T cell immunity is 
age-dependent and may be influenced by Vδ2+Vγ9+ T cell frequency. Since there 
was no significant VE at 6 months in these infants, these vaccine regimens will 
likely not be pursued further in this age group.