title: Phase 1 trial of malaria transmission blocking vaccine candidates Pfs25 and Pvs25 formulated with montanide ISA 51.
abstract: BACKGROUND
  Pfs25 and Pvs25, surface proteins of mosquito stage of the malaria parasites P. falciparum and P. vivax, respectively, are leading candidates for vaccines preventing malaria transmission by mosquitoes. This single blinded, dose escalating, controlled Phase 1 study assessed the safety and immunogenicity of recombinant Pfs25 and Pvs25 formulated with Montanide ISA 51, a water-in-oil emulsion.
  
  
  RESULTS
  The trial was conducted at The Johns Hopkins Center for Immunization Research, Washington DC, USA, between May 16, 2005-April 30, 2007. The trial was designed to enroll 72 healthy male and non-pregnant female volunteers into 1 group to receive adjuvant control and 6 groups to receive escalating doses of the vaccines. Due to unexpected reactogenicity, the vaccination was halted and only 36 volunteers were enrolled into 4 groups: 3 groups of 10 volunteers each were immunized with 5 microg of Pfs25/ISA 51, 5 microg of Pvs25/ISA 51, or 20 microg of Pvs25/ISA 51, respectively. A fourth group of 6 volunteers received adjuvant control (PBS/ISA 51). Frequent local reactogenicity was observed. Systemic adverse events included two cases of erythema nodosum considered to be probably related to the combination of the antigen and the adjuvant. Significant antibody responses were detected in volunteers who completed the lowest scheduled doses of Pfs25/ISA 51. Serum anti-Pfs25 levels correlated with transmission blocking activity.
  
  
  CONCLUSIONS
  It is feasible to induce transmission blocking immunity in humans using the Pfs25/ISA 51 vaccine, but these vaccines are unexpectedly reactogenic for further development. This is the first report that the formulation is associated with systemic adverse events including erythema nodosum.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00295581.
authors.affiliation: Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases, Rockville, Maryland, United States of America. yiwu@niaid.nih.gov
authors.forename: Yimin
authors.initials: Y
authors.lastname: Wu
authors.forename: Ruth D
authors.initials: RD
authors.lastname: Ellis
authors.forename: Donna
authors.initials: D
authors.lastname: Shaffer
authors.forename: Erica
authors.initials: E
authors.lastname: Fontes
authors.forename: Elissa M
authors.initials: EM
authors.lastname: Malkin
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Mahanty
authors.forename: Michael P
authors.initials: MP
authors.lastname: Fay
authors.forename: David
authors.initials: D
authors.lastname: Narum
authors.forename: Kelly
authors.initials: K
authors.lastname: Rausch
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Miles
authors.forename: Joan
authors.initials: J
authors.lastname: Aebig
authors.forename: Andrew
authors.initials: A
authors.lastname: Orcutt
authors.forename: Olga
authors.initials: O
authors.lastname: Muratova
authors.forename: Guanhong
authors.initials: G
authors.lastname: Song
authors.forename: Lynn
authors.initials: L
authors.lastname: Lambert
authors.forename: Daming
authors.initials: D
authors.lastname: Zhu
authors.forename: Kazutoyo
authors.initials: K
authors.lastname: Miura
authors.forename: Carole
authors.initials: C
authors.lastname: Long
authors.forename: Allan
authors.initials: A
authors.lastname: Saul
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; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology*; D000954:Antigens, Surface / Q000737:chemistry / Q000276:immunology*; D018562:Disease Transmission, Infectious; D005260:Female; D006801:Humans; D017780:Malaria Vaccines / Q000009:adverse effects* / Q000737:chemistry / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control / Q000635:transmission; D016780:Malaria, Vivax / Q000517:prevention & control / Q000635:transmission; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D008875:Middle Aged; D009829:Oleic Acids / Q000008:administration & dosage* / Q000737:chemistry; D010963:Plasmodium falciparum / Q000276:immunology; D010966:Plasmodium vivax / Q000276:immunology; D015800:Protozoan Proteins / Q000009:adverse effects* / Q000737:chemistry / Q000276:immunology*; D011994:Recombinant Proteins / Q000009:adverse effects* / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D000953:Antigens, Protozoan; D000954:Antigens, Surface; D017780:Malaria Vaccines; D009829:Oleic Acids; C071284:Pfs25 protein, Plasmodium falciparum; D015800:Protozoan Proteins; C121473:Pvs25 protein, P vivax; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; C477385:montanide ISA 51; C099774:transmission-Blocking Vaccine based on Pfs25; D008353:Mannitol