Feasibility of direct venous inoculation of the radiation-attenuated Plasmodium falciparum whole sporozoite vaccine in children and infants in Siaya, western Kenya.

PfSPZ Vaccine, composed of radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum sporozoites, is administered by direct venous inoculation (DVI) for maximal efficacy against malaria. A critical issue for advancing vaccines that are administered intravenously is the ability to efficiently administer them across multiple age groups. As part of a pediatric safety, immunogenicity, and efficacy trial in western Kenya, we evaluated the feasibility and tolerability of DVI, including ease of venous access, injection time, and crying during the procedure across age groups. Part 1 was an age de-escalation, dose escalation trial in children aged 13 months-5 years and infants aged 5-12 months; part 2 was a vaccine efficacy trial including only infants, using the most skilled injectors from part 1. Injectors could use a vein viewer, if needed. A total of 1222 injections (target 0.5 mL) were initiated by DVI in 511 participants (36 were 5-9-year-olds, 65 were 13-59-month-olds, and 410 infants). The complete volume was injected in 1185/1222 (97.0%) vaccinations, 1083/1185 (91.4%) achieved with the first DVI. 474/511 (92.8%) participants received only complete injections, 27/511 (5.3%) received at least one partial injection (<0.5 mL), and in 10/511 (2.0%) venous access was not obtained. The rate of complete injections by single DVI for infants improved from 77.1% in part 1 to 92.8% in part 2. No crying occurred in 51/59 (86.4%) vaccinations in 5-9-year-olds, 25/86 (29.1%) vaccinations in 13-59-month-olds and 172/1067 (16.1%) vaccinations in infants. Mean administration time ranged from 2.6 to 4.6 minutes and was longer for younger age groups. These data show that vaccination by DVI was feasible and well tolerated in infants and children in this rural hospital in western Kenya, when performed by skilled injectors. We also report that shipping and storage in liquid nitrogen vapor phase was simple and efficient. (Clinicaltrials.gov NCT02687373).

Evidence for strain-specific protective immunity against blood-stage parasites of Plasmodium cynomolgi in toque monkey.

We have conducted experiments to test the induction of strain-specific protective immunity against Plasmodium cynomolgi infections in toque monkeys. Plasmodium cynomolgi is closely related biologically and genetically to the human malaria parasite, P. vivax. Two groups of monkeys were immunized against either of two strains of P. cynomolgi, namely PcCeylon and Pc746, by giving two successive drug-cured infections with asexual blood-stage parasites of one or the other strain, 12-weeks apart. To test for strain-specific protective immunity these infection-immunized monkeys were challenged 8 weeks later with a mixture of asexual blood-stage parasites of both strains. A pyrosequencing-based assay was used to quantify the proportion of parasites that survived in the challenge infections. The assay was based on a SNP within the P. cynomolgi Merozoite Surface Protein-1 gene. Compared to their behaviour in nonimmunized monkeys, the growth of parasites of the homologous (immunizing) strain in mixed-strain challenge infections in the immunized monkeys were reduced relative to that of the nonimmunizing strain. These results indicate the development of blood infection-induced strain-specific protective immunity against P. cynomolgi in toque monkeys. The work prepares for using genetic analysis to identify target antigens of strain-specific protective immunity in this host and malaria parasite combination.