People with malaria often show altered immune responses to many illnesses and vaccines. This
means that the malaria might cause immune suppression. It is not clear how or which vaccines
are impacted by malaria. It is also not clear if the impacts are such that people should be
preemptively treated before they get vaccinations. Researchers want to see if there is a link
between taking an antimalaria drug prior to getting vaccines and the immune response to those
vaccines. To do this, they will study people who are taking part in certain NIAID studies.
To compare the proportion of PD1+ CD4 T cells among all T cells in vaccine immune responses
in adults who have or have not received antimalarials prior to getting a Menactra vaccine.
Healthy Malian adults who:
Were previously enrolled in NIAID Protocol 13-I-N109 or 15-I-0044
Reside in Bancoumana and neighboring villages
Are not pregnant
Participants will be screened with a physical exam.
Participants will get the vaccines listed below as part of Protocol 13-I-N109 or 15-I-0044.
This study will follow their schedule.
At each visit, participants will give a blood sample. They will also have a physical exam.
Each visit will last 1 to 2 hours.
At visit 1, participants will get a hepatitis vaccine.
Two weeks later, participants may get the antimalarial drug Coartem . They will be chosen at
Two weeks later, participants will get Menactra .
Participants will have 5 follow-up visits after they get Menactra .
The study will last up to 4 months.
Malaria patients often show altered immune responses, not only to malaria parasites but also
to unrelated pathogens (eg, HIV, EBV, salmonella, helminthes) and antigens, including routine
vaccines, suggesting that there is an active immune suppression or more accurately perhaps,
immunomodulation, occurring during the course of malaria infection. How and which vaccines
are impacted by clinical malaria or asymptomatic parasitemia is not completely clear and nor
is whether the impacts are significant enough to recommend delaying or pre-emptively treating
individuals prior to vaccinations.
Up to 75 adults will be recruited from volunteers enrolled in NIAID protocol 13-I-N109 and
NIAID protocol 15-I-0044 who after unblinding have opted to receive or complete the
comparator vaccine series: Euvax (Hepatitis B) or TWINRIX (Hepatitis B) and Menactra
(Meningococcal). This longitudinal study will be conducted in Bancoumana and neighboring
villages in Mali. In September 2015, up to 50 adults presenting for their Vaccination #3 of
Euvax will be enrolled from NIAID protocol 13-I-N109. In October 2015, up to 25 adults
presenting for their Study Day 168 will be enrolled following unblinding from NIAID protocol
Following receipt of their Euvax B or TWINRIX vaccination, subjects will be randomized to
receive or not receive a course of Coartem (artemether-lumefantrine) 2 weeks prior to their
scheduled Menactra vaccination. They will then be followed for approximately 3 months post
receipt of Menactra . Samples will be collected from the adults at the time of prior to and
following receipt of both vaccinations and assessed in ex vivo assays for markers of T-cell
suppression as the primary outcome of this study. For our secondary outcomes, we will examine
levels of regulatory T cells, measure T cell responses in stimulation assays, and survey
parasitemia by blood smear and by polymerase chain reaction assays. We expect that levels of
T-cell suppression and regulatory T cells will be similar between groups before antimalarial
treatment or malaria infection, but after treatment or in those subjects that remain
uninfected these levels will be significantly lower as compared to the untreated and or
|Condition or disease
|First Submitted Date||September 05, 2015|
|Last Update Posted Date||February 22, 2018|
|Start Date||September 04, 2015|
|Actual Completion Date||August 11, 2017|
|Primary Completion Date||September 04, 2015|
|Results First Submitted Date||N/A|
|Received Results Disposit Date||N/A|
Current Primary Outcome Measures
Proportion of T cells expressing PD-1 among all T cells on Study Day 42
[Time Frame: Study Day 42]
Original Primary Outcome Measures
Current Secondary Outcome Measures
Original Secondary Outcome Measures
|Brief Title||Markers of T Cell Suppression: Antimalarial Treatment and Vaccine Responses in Healthy Malian Adults|
|Official Title||Markers of T Cell Suppression: Antimalarial Treatment and Vaccine Responses in Healthy Malian Adults|
|Target Follow-Up Duration|| N/A|
|Completion Date||August 11, 2017|
- Enrolled, completed unblinding, and have opted to receive the comparator vaccines in
either NIAID Protocol 13-I-N109 or 15-I-0044
- In good general health and without any clinically significant medical history
- Willing to have blood samples stored for future research
- Known resident of Bancoumana or surrounding area
- Known to be pregnant (by history)
- Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine,
rheumatologic, autoimmune, hematological, oncologic, psychiatric, or renal disease by
history and/or physical examination
- Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator
affects the ability of the participant to understand and comply with the study
- Prior to Study Day 0, receipt of a live vaccine within the past 4 weeks or a killed
vaccine within the past 2 weeks
- Use of chronic (greater than or equal to 14 days) oral or intravenous corticosteroids
(excluding topical or nasal) at immunosuppressive doses (eg, prednisone > 10 mg/day)
or immunosuppressive drugs within 30 days of Study Day 0
- Known allergies or contraindications to study treatment (Coartem
[artemether//lumefantrine]) or vaccines (Euvax B or TWINRIX and Menactra )
- Other condition that in the opinion of the investigator would jeopardize the safety or
rights of a participant participating in the trial, interfere with the evaluation of
the study objectives, or would render the subject unable to comply with the protocol
|Age||18 Years to 50 Years|
|Accepts Healthy Volunteers||Accepts Healthy Volunteers|
|Listed Location Countries
|Other Study ID Numbers
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
|IPD Sharing Statement
|Responsible Party||, |
Sara A Healy, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)