Markers of T Cell Suppression: Antimalarial Treatment and Vaccine Responses in Healthy Malian Adults
Condition: Malaria
MeSH terms: Malaria
Study type: Observational

Summary: 
      Background:

      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.

      Objectives:

      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.

      Eligibility:

      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

      Design:

      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
      random.

      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.

      ...
    

Detailed description: 
      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.
    

Observational model: Cohort
Time perspective: Prospective
Keywords: Immune; Parasitemia; Menactra; Polymerase Chain Reaction (PCR); Coartem