Target Antigens Induced by Plasmodium Falciparum Sporozoite Immunization Under Chemoprophylaxis

• Status: Completed
• Trial end date: 2015-07-01
• Target enrollment: 0
• Participant gender: All

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, there is desperate need for an effective vaccine. Though a number of vaccine-candidates have been developed, they have yet to achieve the level of efficacy necessary to eliminate malaria. It has been shown previously that healthy human volunteers bitten by malaria-infected mosquitoes while taking chloroquine, medicine that prevents malaria, are fully protected against a subsequent malaria challenge. This is called CPS-immunization. The unprecedented effectiveness of CPS-immunization makes it a good model to identify what immune responses protect against malaria, to further guide vaccine development. In this study we will use CPS-immunization to induce protection against malaria in healthy subjects and then analyse their immune response to a malaria challenge infection.

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Radboud University
• Collaborator: Bill and Melinda Gates Foundation
• Treatments: Atovaquone; Atovaquone, proguanil drug combination; Chloroquine; Chloroquine diphosphate; Proguanil; Vaccines

Criteria

Inclusion Criteria:

1. Subject is aged ≥ 18 and ≤ 35 years and in good health.

2. Subject has adequate understanding of the procedures of the study and agrees to abide thereby.

3. Subject is able to communicate well with the investigator, is available to attend all study visits, lives in proximity to the trial centre or is willing to stay in a hotel close to the trial centre during part of the study (day 5 post-infection until three days post-treatment). The subject will remain within the Netherlands during the challenge period, not travel to a malaria-endemic area during the study period, and is reachable (24/7) by mobile telephone throughout the entire study period.

4. Subject agrees to inform his/her general practitioner (GP) about participation in the study and to sign a request to release by the GP any relevant medical information concerning possible contra-indications for participation.

5. Subject agrees to refrain from blood donation to Sanquin or for other purposes throughout the study period and for a defined period thereafter according to Sanquin guidelines.

6. For female subjects: agrees to use adequate contraception and not to breastfeed for the duration of study.

7. Subject has signed informed consent.

Exclusion Criteria:

1. Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions, which could compromise the health of the volunteer during the study or interfere with the interpretation of the study results. These include, but are not limited to, any of the following:

1.1 Body weight <50 kg or Body Mass Index (BMI) <18.0 or >30.0 kg/m2 at screening.

1.2 A heightened risk of cardiovascular disease, as determined by: an estimated ten year risk of fatal cardiovascular disease of ≥5% at screening, as determined by the Systematic Coronary Risk Evaluation; history, or evidence at screening, of clinically significant arrhythmia's, prolonged QT-interval or other clinically relevant ECG abnormalities; or a positive family history of cardiac events in 1st or 2nd degree relatives <50 years old.

1.3 Functional asplenia, sickle cell trait/disease, thalassaemia trait/disease or G6PD deficiency.

1.4 History of epilepsy in the period of five years prior to study onset. 1.5 Positive Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) screening tests.

1.6 Chronic use of i) immunosuppressive drugs, ii) antibiotics, iii) or immune modifying drugs within three months prior to study onset (inhaled and topical corticosteroids and oral anti-histamines exempted) or expected use of such during the study period.

1.7 History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, in the past 5 years.

1.8 Any history of treatment for severe psychiatric disease in the past year. 1.9 History of drug or alcohol abuse one year prior to study onset, or positive urine toxicology test for cocaine or amphetamines at screening or prior to infection.

2. Females: positive urine pregnancy test at screening or prior to infection.

3. Any history of malaria, positive serology for P. falciparum, or previous participation in any malaria study.

4. Known hypersensitivity to or contra-indications to any antimalarials, or history of severe reactions to mosquito bites.

5. Receipt of any vaccinations in the 3 months prior to the start of the study or plans to receive any other vaccinations during the study period or up to 8 weeks thereafter.

6. Participation in any other clinical study in the 30 days prior to the start of the study or during the study period.

7. Being an employee or student of the department of Medical Microbiology of the Radboudumc or the department of Internal Medicine.

8. Any other condition or situation that would, in the opinion of the investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.