Markers of T Cell Suppression: Antimalarial Treatment and Vaccine Responses in Healthy Malian Adults

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 15-I-0044.

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 infected subjects.

• INCLUSION
• 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

EXCLUSION

• 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 protocol
• 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