Improving the Efficacy of Experimental Malaria Vaccine AMA1-C1/Alhydrogel® (Registered Trademark)
Condition: Healthy Volunteer; HV
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will evaluate the safety and efficacy of the experimental malaria vaccine
      AMA1-C1/Alhydrogel® (Registered Trademark) and determine whether a new, additional component
      of the vaccine may increase its effectiveness. Malaria is a debilitating and potentially
      fatal blood disease transmitted by a parasite found in certain mosquitoes. The AMA1-C1
      vaccine has been designed to create an immune response against the parasite and prevent the
      disease. The purpose of the study is to determine whether the additional component-protein
      pieces known as CpG- improves the immune response to the vaccine without causing problematic
      side effects.

      Volunteers must be healthy adults between 18 and 45 years old. Individuals who have had
      malaria in the past or have recently traveled to areas where malaria is endemic will be
      excluded from the study. Candidates will be screened with a physical examination, blood
      tests, and medical history.

      Participants will be involved in a three-stage study. In the first stage, a group of
      participants will receive either a high dose of the vaccine alone or a low dose combined with
      the CpG protein. In the second stage, a different group of participants will receive a high
      dose of the vaccine alone or a high dose combined with CpG. In the third stage, a larger
      group of participants will receive a high dose of the vaccine alone or a high dose combined
      with CpG. The vaccine will be injected into the muscle of the upper arm, and all participants
      will receive three doses of the vaccine with 28 days between doses to monitor possible
      reactions and side effects. Participants will be monitored for 30 minutes after each
      injection and will record any symptoms they experience over the six days after receiving
      their dose. In addition, participants will be examined over the course of six months during
      and after the trial with physical exams and blood and urine tests.
    

Detailed description: 
      Purpose: This study will evaluate the safety and immunogenicity of the experimental malaria
      vaccine AMA1-C1/Alhydrogel® (Registered Trademark), and the ability of the TLR-9 agonist CPG
      7909 oligodexoynucleotide (ODN) to augment antibody response to the vaccine and alter the
      Th1/Th2 bias. The vaccine preparations to be studied contain an equal mixture of AMA1 from
      two different clones of Plasmodium falciparum (FVO and 3D7), both produced separately as
      recombinant proteins expressed by Pichia pastoris (PpAMA-1 FVO and PpAMA-1 3D7). Bulk PpAMA-1
      antigens were purified from culture medium of transformed yeast grown in a 60L fermenter. The
      correctly folded PpAMA-1 was purified from this mixture by a combination of affinity, ionic,
      hydrophobic and gel filtration chromatography. Purified PpAMA-1 FVO and PpAMA-1 3D7 were
      subsequently mixed and adsorbed onto aluminum hydroxide gel (Alhydrogel® (Registered
      Trademark)). The CPG 7909 ODN formulation used in this study (CPG 7909) is manufactured by
      Coley Pharmaceutical Group. Subjects will be randomly assigned to receive Alhydrogel®
      (Registered Trademark) formulated vaccine with or without CPG 7909 in a point of use
      formulation.

      Research Environment: The study will be conducted at the University of Rochester Vaccine and
      Treatment Evaluation Unit (VTEU).

      Subjects: Subjects for this study will be healthy adults between the ages of 18 and 45 years
      with no history of malaria or of recent travel to malaria-endemic areas. Subjects will be
      enrolled in three consecutive dose-escalation cohorts with review by a Safety Monitoring
      Committee between cohorts.

      Subject participation: Subjects will receive three vaccinations with the AMA1-C1/Alhydrogel®
      (Registered Trademark) vaccine formulated in Alhydrogel® (Registered Trademark) with or
      without CPG 7909 adjuvant over 2 months (0, 1, 2 months) by intramuscular (IM) injection.
      Subjects will have multiple blood samples obtained over the next 6 months.

      Variables to be Investigated: Samples will be tested for binding antibody to AMA1 and for
      ability to inhibit the growth of plasmodia in vitro. In addition, antigen-specific activated
      B cells in peripheral blood will be enumerated, as well as the relative ratio of
      antigen-specific Th1-like and Th2-like T cells.

      Risk/Benefits: The risks of participating in this study are those associated with
      administration of AMA1-C1/Alhydrogel® (Registered Trademark) and of CPG 7909, and include
      local pain, systemic inflammatory responses including fever and influenza-like symptoms, and
      induction of autoimmune responses. As with any other investigational vaccine, there are
      unknown risks. Subjects may derive no benefit from participation in this study. Development
      of effective vaccines to prevent malaria is an important societal benefit.

      Confidentiality: Volunteers will have code numbers and will not be identified by name.
    

Intervention name(s): AMA1-C1/Alhydrogel + CpG 7909
Intervention type(s): Drug
Intervention MeSH terms: Aluminum Hydroxide
Primary purpose: Treatment
Keywords: Human; Clinical Trial; Mosquito; Healthy Volunteer; HV