Last Updated: 26/06/2020

Repeat direct venous inoculation of Plasmodium falciparum sporozoites, strain NF54 and clone 7G8, in healthy adult volunteers naturally exposed to malaria in Gabon: a randomized open-label study LaCHMI-2 (L2)

Objectives

 The overall gold of this project is to investigate if repeat controlled human malaria infections (CHMI) with Plasmodium falciparum sporozoites (PfSPZ) challenge (NF54) improves immunity against homologous (PfSPZ Challenge (NF54)) and heterologous (PfSPZ Challenge (7G8)) CHMI. The outcome thereof should help to develop more efficacious immunization regimens against malaria.

Principal Investigators / Focal Persons

Matthew McCall

Rationale and Abstract

Malaria is the most important parasitic disease worldwide and a major cause of paediatric morbidity and mortality in sub-Saharan Africa. An efficacious vaccine will be essential to control and eliminate malaria as well as to contain drug-resistant parasite strains. However, the development thereof is hindered in part by our incomplete understanding of protective immunity against this disease. Controlled human malaria infections (CHMI) are a valuable tool for studying anti-malarial immunity. The development by Sanaria Inc. of viable, aseptic, purified, vialed, cryopreserved Plasmodium falciparum (Pf) sporozoites (SPZ) for direct intravenous inoculation (DVI), has allowed for the first time the conduct of CHMIs in endemic populations (under otherwise resource-poor settings) to study naturally-acquired immunity. Two different products are available: PfSPZ Challenge (NF54) and PfSPZ Challenge (7G8), containing respectively the NF54 strain and 7G8 clone of P. falciparum. At the Centre de Recherches Médicales de Lambaréné (CERMEL) in Gabon, an area of high malaria endemicity, two CHMI studies have previously been performed in lifelong-exposed adults using 3,200 PfSPZ Challenge (NF54), a dose that consistently leads to malaria in naïve individuals. Amongst Gabonese adults, three levels of naturally-acquired anti-parasitic immunity could be distinguished: 1. Protection (no parasitemia, no symptoms, no antimalarial therapy required) 2. Control (parasitemia, no symptoms, no antimalarial therapy required) 3. Malaria (parasitemia, symptoms, antimalarial therapy required). However, it is unclear if the level of naturally-acquired immunity in any given individual is constant or can be improved.

Date

Mar 2019 — Nov 2020

Project Site

Gabon

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