Laboratory Evaluation of Pregnancy Malaria Vaccine Candidates/In-vitro Testing of Pregnancy Malaria Vaccine Candidates

Malaria Clinical Trial

Official title:

In-Vitro Testing of Pregnancy Malaria Vaccine Candidates

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02471378
• Other study ID #: 999915147
• Secondary ID: 15-I-N147
• Status: Recruiting
• Start date: July 28, 2015
• Est. completion date: June 30, 2024

Study information

• Verified date: November 2, 2023
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Michal Fried, Ph.D.
• Phone: (240) 747-7880
• Email: michal.fried[@]nih.gov
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Background:

• Malaria is a disease that affects many people in African countries. It is caused by germs that are spread by mosquito bites. It can be fatal if not diagnosed and treated right away. Children younger than 5 and pregnant women are most at risk to get malaria. Researchers want to create a vaccine that will prevent malaria infection during pregnancy.

Objectives:

• To create a vaccine that will prevent malaria infection during pregnancy. To assess possible vaccines using in-vitro tests with parasites taken from pregnant women.

Eligibility:

• Pregnant women ages 15 25

Design:

• The study site is an area in Mali, West Africa.

• Participants:

• Will have blood drawn.

• Will give consent for the blood sample to be used for future research.

• May have a physical exam.

• Participants who have malaria or anemia will get treatment.

Description:

Malaria caused by Plasmodium falciparum continues to be a global problem with devastating consequences. Pregnancy malaria is associated with low birth weight (LBW), maternal anemia, and gestational hypertension; and both inflammation and the fetal response to infection may contribute to these poor outcomes. Pregnancy malaria (PM) is caused by P. falciparum-infected erythrocytes that bind to the placental receptor chondroitin sulfate A (CSA) and sequester in the placenta, where they cause disease and death for the mother and her offspring. Women become resistant to pregnancy malaria as they acquire antibodies that target surface proteins of placental parasites. Malaria vaccine candidates targeting the parasite s liver stage or blood stage may not protect pregnant women and their unborn children. The primary hypothesis in this study is that antibodies raised in animals against recombinant pregnancy malaria vaccine candidates will have a similar functional activity as naturally acquired antibodies. Up to 1597 malaria-infected pregnant women will be recruited into a cross sectional study that will be conducted in Ouelessebougou and neighboring districts, Mali. Women presenting for antenatal visit at the health centers in Ouelessebougou District will be enrolled. Samples collected from the women will be used in in-vitro assays to assess the functional activity of immunoglobulin G (IgG) raised against pregnancy malaria vaccine candidates as the primary outcome of this study. For our secondary outcomes, we will examine functional activity of naturally acquired antibodies specific to the vaccine candidates. Functional activity by IgG to vaccine candidates will be compared to the activity obtained with control proteins using appropriate statistical methods, including adjustment for possible confounders such as parasite density in the assay, to determine if the candidates elicit the type of immune response observed in naturally exposed population.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 4791
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 15 Years to 25 Years

Eligibility

• INCLUSION CRITERIA:

A study participant must satisfy the following criteria to be enrolled in this study:

• Pregnant women aged 15-25 years

• Able to provide consent for self

• Malaria positive by rapid diagnostic test (RDT)

EXCLUSION CRITERIA:

• Severe anemia defined as HGB<7 gr/dL, that may be worsened by 10 mL phlebotomy

• Conditions that in the judgment of the investigator could increase the risk to the volunteer

• Prior enrollment to the study during the same pregnancy

Related Conditions & MeSH terms

• Malaria

Locations

Country	Name	City	State
Mali	Ouelessebougou Clinical Research Center	Bamako

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

Mali, 

References & Publications (3)

Bordbar B, Tuikue-Ndam N, Bigey P, Doritchamou J, Scherman D, Deloron P. Identification of Id1-DBL2X of VAR2CSA as a key domain inducing highly inhibitory and cross-reactive antibodies. Vaccine. 2012 Feb 8;30(7):1343-8. doi: 10.1016/j.vaccine.2011.12.065. Epub 2012 Jan 5. — View Citation

Fried M, Avril M, Chaturvedi R, Fernandez P, Lograsso J, Narum D, Nielsen MA, Oleinikov AV, Resende M, Salanti A, Saveria T, Williamson K, Dicko A, Scherf A, Smith JD, Theander TG, Duffy PE. Multilaboratory approach to preclinical evaluation of vaccine immunogens for placental malaria. Infect Immun. 2013 Feb;81(2):487-95. doi: 10.1128/IAI.01106-12. Epub 2012 Dec 3. — View Citation

Fried M, Nosten F, Brockman A, Brabin BJ, Duffy PE. Maternal antibodies block malaria. Nature. 1998 Oct 29;395(6705):851-2. doi: 10.1038/27570. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measure of functional activity of animal IgG against vaccine candidates to block binding of fresh pregnancy malaria isolates to the placental receptor CSA		Approximately 1 year