Testing Vaccines To Prevent Plasmodium vivax Infection Using a Human Challenge Model

A safe and reproducible Plasmodium vivax infectious challenge method is required to evaluate the efficacy of malaria vaccine candidates. Two phase II clinical trials have been successfully conducted at the Malaria Vaccine and Drug Development Center in Cali, Colombia to establish such a model. In a first trial 18 healthy adult, malaria-naïve volunteers were randomly allocated to Groups A–C and exposed to 3 ± 1, 6 ± 1, and 9 ± 1 bites of Anopheles albimanus mosquitoes infected with P. vivax , respectively. Seventeen volunteers developed signs and symptoms consistent with malaria, and geometric mean prepatent periods of 11.1 days (9.3–11) for Group A; 10.8 days (9.8–11.9) for Group B; and 10.6 days (8.7–12.4) for Group C, with no statistically significant difference among groups (Kruskal-Wallis, P = 0.70). One volunteer exposed to eight mosquito bites did not develop a parasitemia. No differences in parasite density were observed and all individuals successfully recovered after anti-malarial treatment. None of the volunteers developed parasite relapses within an 18-month follow-up. In the second trial 17 Duffy (+) and five Duffy (-) subjects were randomly allocated into three (A--C) groups and were exposed to the bites of 2--4 Anopheles mosquitoes infected with P. vivax derived from 3 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 malaria within 16 days after exposure.  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-naïve volunteers, suitable for assessing antimalarials and vaccine efficacy trials. In conclusion, malaria-naïve volunteers can be safely and reproducibly infected with bites of 2–10 An. albimanus mosquitoes carrying P. vivax sporozoites. This challenge method is suitable for anti-malarial drug testing as well as for vaccine testing, including P.vivax irradiated sporozoites.