title: Safety and reactogenicity of an MSP-1 malaria vaccine candidate: a randomized phase Ib dose-escalation trial in Kenyan children.
abstract: OBJECTIVE
  Our aim was to evaluate the safety, reactogenicity, and immunogenicity of an investigational malaria vaccine.
  
  
  METHODS
  This was an age-stratified phase Ib, double-blind, randomized, controlled, dose-escalation trial. Children were recruited into one of three cohorts (dosage groups) and randomized in 2:1 fashion to receive either the test product or a comparator.
  
  
  METHODS
  The study was conducted in a rural population in Kombewa Division, western Kenya.
  
  
  METHODS
  Subjects were 135 children, aged 12-47 mo.
  
  
  METHODS
  Subjects received 10, 25, or 50 microg of falciparum malaria protein 1 (FMP1) formulated in 100, 250, and 500 microL, respectively, of AS02A, or they received a comparator (Imovax (rabies vaccine).
  
  
  METHODS
  We performed safety and reactogenicity parameters and assessment of adverse events during solicited (7 d) and unsolicited (30 d) periods after each vaccination. Serious adverse events were monitored for 6 mo after the last vaccination.
  
  
  RESULTS
  Both vaccines were safe and well tolerated. FMP1/AS02A recipients experienced significantly more pain and injection-site swelling with a dose-effect relationship. Systemic reactogenicity was low at all dose levels. Hemoglobin levels remained stable and similar across arms. Baseline geometric mean titers were comparable in all groups. Anti-FMP1 antibody titers increased in a dose-dependent manner in subjects receiving FMP1/AS02A; no increase in anti-FMP1 titers occurred in subjects who received the comparator. By study end, subjects who received either 25 or 50 microg of FMP1 had similar antibody levels, which remained significantly higher than that of those who received the comparator or 10 microg of FMP1. A longitudinal mixed effects model showed a statistically significant effect of dosage level on immune response (F(3,1047) = 10.78, or F(3, 995) = 11.22, p < 0.001); however, the comparison of 25 microg and 50 microg recipients indicated no significant difference (F(1,1047) = 0.05; p = 0.82).
  
  
  CONCLUSIONS
  The FMP1/AS02A vaccine was safe and immunogenic in malaria-exposed 12- to 47-mo-old children and the magnitude of immune response of the 25 and 50 microg doses was superior to that of the 10 microg dose.
authors.affiliation: United States Army Medical Research Unit-Kenya, Nairobi, Kenya. mwithers@us.army.mil
authors.forename: Mark R
authors.initials: MR
authors.lastname: Withers
authors.forename: Denise
authors.initials: D
authors.lastname: McKinney
authors.forename: Bernhards R
authors.initials: BR
authors.lastname: Ogutu
authors.forename: John N
authors.initials: JN
authors.lastname: Waitumbi
authors.forename: Jessica B
authors.initials: JB
authors.lastname: Milman
authors.forename: Odika J
authors.initials: OJ
authors.lastname: Apollo
authors.forename: Otieno G
authors.initials: OG
authors.lastname: Allen
authors.forename: Kathryn
authors.initials: K
authors.lastname: Tucker
authors.forename: Lorraine A
authors.initials: LA
authors.lastname: Soisson
authors.forename: Carter
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authors.lastname: Diggs
authors.forename: Amanda
authors.initials: A
authors.lastname: Leach
authors.forename: Janet
authors.initials: J
authors.lastname: Wittes
authors.forename: Filip
authors.initials: F
authors.lastname: Dubovsky
authors.forename: V Ann
authors.initials: VA
authors.lastname: Stewart
authors.forename: Shon A
authors.initials: SA
authors.lastname: Remich
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: W Ripley
authors.initials: WR
authors.lastname: Ballou
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Holland
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Lyon
authors.forename: Evelina
authors.initials: E
authors.lastname: Angov
authors.forename: José A
authors.initials: JA
authors.lastname: Stoute
authors.forename: Samuel K
authors.initials: SK
authors.lastname: Martin
authors.forename: D Gray
authors.initials: DG
authors.lastname: Heppner