Abstract
Immunization of volunteers under chloroquine prophylaxis by bites of Plasmodium falciparum sporozoite (PfSPZ)–infected mosquitoes induces > 90% protection against controlled human malaria infection (CHMI). We studied intradermal immunization with cryopreserved, infectious PfSPZ in volunteers taking chloroquine (PfSPZ chemoprophylaxis vaccine [CVac]). Vaccine groups 1 and 3 received 3× monthly immunizations with 7.5 × 104 PfSPZ. Control groups 2 and 4 received normal saline. Groups 1 and 2 underwent CHMI (#1) by mosquito bite 60 days after the third immunization. Groups 3 and 4 were boosted 168 days after the third immunization and underwent CHMI (#2) 137 days later. Vaccinees (11/20, 55%) and controls (6/10, 60%) had the same percentage of mild to moderate solicited adverse events. After CHMI #1, 8/10 vaccinees (group 1) and 5/5 controls (group 2) became parasitemic by microscopy; the two negatives were positive by quantitative real-time polymerase chain reaction (qPCR). After CHMI #2, all vaccinees in group 3 and controls in group 4 were parasitemic by qPCR. Vaccinees showed weak antibody and no detectable cellular immune responses. Intradermal immunization with up to 3 × 105 PfSPZ-CVac was safe, but induced only minimal immune responses and no sterile protection against Pf CHMI.
Highlights
Malaria accounted for an estimated 198 million clinical cases and 584,000 deaths in 2013, with children under 5 years of age in sub-Saharan Africa most severely affected.[1]
We have previously shown that healthy malarianaive volunteers can be fully protected against a controlled human malaria infection (CHMI) by mosquito bite with a homologous Pf strain for more than 2 years after three immunizations under chloroquine prophylaxis by bites from 12 to 15 Plasmodium falciparum sporozoite (PfSPZ)-infected mosquitoes
One subject in vaccine group 3 received tetanus vaccination after the third immunization session and was later excluded based on the safety procedures adopted for CHMI #2, because of the serious AE (SAE) after CHMI #1
Summary
Malaria accounted for an estimated 198 million clinical cases and 584,000 deaths in 2013, with children under 5 years of age in sub-Saharan Africa most severely affected.[1]. Progress in the clinical development of efficient immunization strategies as a forerunner of an effective malaria vaccine has been facilitated by controlled human malaria infections (CHMIs). CHMIs involve small groups of malaria-naive volunteers exposed to the bites of Plasmodium falciparum sporozoite (PfSPZ)–infected laboratory-reared anopheline mosquitoes. We have previously shown that healthy malarianaive volunteers can be fully protected against a CHMI by mosquito bite with a homologous Pf strain for more than 2 years after three immunizations under chloroquine prophylaxis by bites from 12 to 15 PfSPZ-infected mosquitoes at monthly intervals (chemoprophylaxis and sporozoites [CPS]).[5,6] Chloroquine kills disease-associated blood stages but does not affect pre-erythrocytic (sporozoite or liver) stages, which are exposed to the host’s immune system. CPSinduced protection is mediated by immunity against preerythrocytic stages.[7]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have