title: Phase 1 trial of the Plasmodium falciparum blood stage vaccine MSP1(42)-C1/Alhydrogel with and without CPG 7909 in malaria naïve adults.
abstract: BACKGROUND
  Merozoite surface protein 1(42) (MSP1(42)) is a leading blood stage malaria vaccine candidate. In order to induce immune responses that cover the major antigenic polymorphisms, FVO and 3D7 recombinant proteins of MSP1(42) were mixed (MSP1(42)-C1). To improve the level of antibody response, MSP1(42)-C1 was formulated with Alhydrogel plus the novel adjuvant CPG 7909.
  
  
  METHODS
  A Phase 1 clinical trial was conducted in healthy malaria-naïve adults at the Center for Immunization Research in Washington, D.C., to evaluate the safety and immunogenicity of MSP1(42)-C1/Alhydrogel +/- CPG 7909. Sixty volunteers were enrolled in dose escalating cohorts and randomized to receive three vaccinations of either 40 or 160 microg protein adsorbed to Alhydrogel +/- 560 microg CPG 7909 at 0, 1 and 2 months.
  
  
  RESULTS
  Vaccinations were well tolerated, with only one related adverse event graded as severe (Grade 3 injection site erythema) and all other vaccine related adverse events graded as either mild or moderate. Local adverse events were more frequent and severe in the groups receiving CPG. The addition of CPG enhanced anti-MSP1(42) antibody responses following vaccination by up to 49-fold two weeks after second immunization and 8-fold two weeks after the third immunization when compared to MSP1(42)-C1/Alhydrogel alone (p<0.0001). After the third immunization, functionality of the antibody was tested by an in vitro growth inhibition assay. Inhibition was a function of antibody titer, with an average of 3% (range -2 to 10%) in the non CPG groups versus 14% (3 to 32%) in the CPG groups.
  
  
  CONCLUSIONS
  The favorable safety profile and high antibody responses induced with MSP1(42)-C1/Alhydrogel + CPG 7909 are encouraging. MSP1(42)-C1/Alhydrogel is being combined with other blood stage antigens and will be taken forward in a formulation adjuvanted with CPG 7909.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier: NCT00320658.
authors.affiliation: Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases/National Institutes of Health, Rockville, Maryland, USA. ellisru@niaid.nih.gov
authors.forename: Ruth D
authors.initials: RD
authors.lastname: Ellis
authors.forename: Laura B
authors.initials: LB
authors.lastname: Martin
authors.forename: Donna
authors.initials: D
authors.lastname: Shaffer
authors.forename: Carole A
authors.initials: CA
authors.lastname: Long
authors.forename: Kazutoyo
authors.initials: K
authors.lastname: Miura
authors.forename: Michael P
authors.initials: MP
authors.lastname: Fay
authors.forename: David L
authors.initials: DL
authors.lastname: Narum
authors.forename: Daming
authors.initials: D
authors.lastname: Zhu
authors.forename: Gregory E D
authors.initials: GE
authors.lastname: Mullen
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Mahanty
authors.forename: Louis H
authors.initials: LH
authors.lastname: Miller
authors.forename: Anna P
authors.initials: AP
authors.lastname: Durbin
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D016778:Malaria, Falciparum / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D017780:Malaria Vaccines