Chemoprophylaxis and Plasmodium Falciparum NF54 Sporozoite Immunization Challenged by Heterologous Infection

Summary

Malaria, a disease caused by the parasite Plasmodium, is one of the world's major infectious diseases. With approximately 627.000 deaths a year, it is both a chief cause of morbidity and mortality as well as a significant contribution to ongoing poverty in endemic countries. Ultimately, the key to malaria control, and hopefully eradication, would be an effective vaccine. Though a number of vaccine-candidates have entered the pipeline of pre-clinical and clinical development, they have yet to achieve the level of efficacy necessary for effective malaria prevention. It has been shown previously that if healthy human volunteers taking chloroquine chemoprophylaxis are repeatedly exposed to Plasmodium parasites through the bites of infected mosquitoes, they are fully protected against a later challenge infection with a 'homologous' (genetically similar) Plasmodium parasite. This process is known as ChemoProphylaxis and Sporozoites, or CPS-immunization. One of the obstacles to developing an effective vaccine is the genetic heterogeneity of malaria parasites. To further consider the development of whole-parasite based vaccines against malaria and in order to better understand the protective immunity induced by CPS-immunization, it is essential to investigate whether heterologous protection against genetically diverse (heterologous) P. falciparum clones can be induced.

This is a single center, randomized, double-blind study to determine whether healthy volunteers immunized with P. falciparum NF54 parasites under chloroquine prophylaxis are protected against a challenge infection with the genetically distinct NF135.C10 or NF166.C8 P. falciparum clones.

Conditions

• Malaria

Interventions

BIOLOGICAL

CPS-immunization

Subjects will be exposed 3 times to bites from 15 NF54 Plasmodium infected mosquitoes during each immunization, while taking chloroquin prophylaxis.

BIOLOGICAL

malaria challenge infection, P. falciparum NF135.C10

Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites.

BIOLOGICAL

malaria challenge infection, P. falciparum NF166.C8

Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF166.C8 sporozoites.

BIOLOGICAL

malaria challenge infection, P. falciparum NF54

Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF54 sporozoites.

DRUG

atovaquone/proguanil

All participants will be treated with atovaquone/proguanil when they develop a malaria infection or on day 28 after malaria challenge infection.

Sponsors & Collaborators

• Bill and Melinda Gates Foundation

  collaborator OTHER

• Radboud University Medical Center

  lead OTHER

Principal Investigators

• Robert W Sauerwein, Prof · Radboud University Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

35 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2014-10-31

Primary Completion

2015-11-30

Completion

2015-11-30

Countries

• Netherlands

Study Locations