Consistent Safety and Infectivity in Sporozoite Challenge Model of Plasmodium vivax in Malaria-Naive Human Volunteers

Abstract

Abstract. A safe and reproducible Plasmodium vivax infectious challenge method is required to evaluate the efficacy of malaria vaccine candidates. Seventeen healthy Duffy (+) and five Duffy (−) subjects were randomly allocated into three (A-C) groups and were exposed to the bites of 2-4 Anopheles albimanus mosquitoes infected with Plasmodium vivax derived from three donors. Duffy (−) subjects were included as controls for each group. Clinical manifestations of malaria and parasitemia were monitored beginning 7 days post-challenge. All Duffy (+) volunteers developed patent malaria infection within 16 days after challenge. Prepatent period determined by thick smear, was longer for Group A (median 14.5 d) than for Groups B and C (median 10 d/each). Infected volunteers recovered rapidly after treatment with no serious adverse events. The bite of as low as two P. vivax -infected mosquitoes provides safe and reliable infections in malaria-naive volunteers, suitable for assessing antimalarial and vaccine efficacy trials.

Plasmodium vivax Sporozoite Production in Anopheles albimanus Mosquitoes for Vaccine Clinical Trials

“…22 The second trial was to determine if infection was dependent on the P. vivax strain used for mosquito feeding, using doses of 3 ± 1 mosquitoes shown to be capable of reproducibly infecting humans. 30 All four batches produced infection in virtually all volunteers.…”

“…22 For the second trial a total of 18 mosquito batches were infected over a similar time period. 30 Eleven batches were discarded because parasite donors presented infectious diseases (Hepatitis, Syphilis, and human T-lymphotrophic virus [HTLV]) ( Table 4 ).…”

“…More than 100 mosquito batches were infected and used to optimize the infection conditions to conduct human sporozoite challenge trials. 22,30 During this process, biosafety measures were established and implemented to minimize volunteer exposure to mosquito bites and the potential for infection by other blood-borne pathogens. Furthermore, conditions for mosquito infection by artificial membrane feeding and mosquito biting of human volunteers were optimized.…”

“…Mosquito infections were variable; nevertheless, a significant number of mosquito batches (50%) developed infections with > 50% of mosquitoes sporozoites positive and thereby suitable for use in human challenge trials. 22,30 Although mosquito infections in this study were highly variable, the process can be considered reliable and reproducible taking into account that multiple confounding factors, including the genetic polymorphism of the P. vivax strain used for mosquito feeding, variability in gametocytemia levels, and degree of gametocyte maturation. Success of infections did not seem to depend on the level of parasitemia or gametocytemia, which is in agreement with previous studies using An.…”

Development of vaccines for Plasmodium vivax malaria

“…Herrera et al have demonstrated the robustness and reproducibility of the P. vivax sporozoite challenge model [80,81], which should allow evaluation of efficacy of both pre-erythrocytic and blood stage P. vivax vaccines. A P. vivax blood stage challenge model that establishes experimental blood stage infection in human subjects by transfer of cryopreserved P. vivax patient isolates [82] could also be used to evaluate efficacy of blood stage P. vivax vaccines.…”