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

Read more

Summary

Introduction

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]

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call