title: Satisfactory safety and immunogenicity of MSP3 malaria vaccine candidate in Tanzanian children aged 12-24 months.
abstract: BACKGROUND
  Development and deployment of an effective malaria vaccine would complement existing malaria control measures. A blood stage malaria vaccine candidate, Merozoite Surface Protein-3 (MSP3), produced as a long synthetic peptide, has been shown to be safe in non-immune and semi-immune adults. A phase Ib dose-escalating study was conducted to assess the vaccine's safety and immunogenicity in children aged 12 to 24 months in Korogwe, Tanzania (ClinicalTrials.gov number: NCT00469651).
  
  
  METHODS
  This was a double-blind, randomized, controlled, dose escalation phase Ib trial, in which children were given one of two different doses of the MSP3 antigen (15 microg or 30 microg) or a control vaccine (Engerix B). Children were randomly allocated either to the MSP3 candidate malaria vaccine or the control vaccine administered at a schedule of 0, 1, and 2 months. Immunization with lower and higher doses was staggered for safety reasons starting with the lower dose. The primary endpoint was safety and reactogenicity within 28 days post-vaccination. Blood samples were obtained at different time points to measure immunological responses. Results are presented up to 84 days post-vaccination.
  
  
  RESULTS
  A total of 45 children were enrolled, 15 in each of the two MSP3 dose groups and 15 in the Engerix B group. There were no important differences in reactogenicity between the two MSP3 groups and Engerix B. Grade 3 adverse events were infrequent; only five were detected throughout the study, all of which were transient and resolved without sequelae. No serious adverse event reported was considered to be related to MSP3 vaccine. Both MSP3 dose regimens elicited strong cytophilic IgG responses (subclasses IgG1 and IgG3), the isotypes involved in the monocyte-dependant mechanism of Plasmodium falciparum parasite-killing. The titers reached are similar to those from African adults having reached a state of premunition. Furthermore, vaccination induced seroconversion in all vaccinees.
  
  
  CONCLUSIONS
  The MSP3 malaria vaccine candidate was safe, well tolerated and immunogenic in children aged 12-24 months living in a malaria endemic community. Given the vaccine's safety and its induction of cytophilic IgG responses, its efficacy against P. falciparum infection and disease needs to be evaluated in Phase 2 studies.
authors.affiliation: National Institute for Medical Research, Tanga Centre, Tanzania. jpalusingu@yahoo.co.uk
authors.forename: John P A
authors.initials: JP
authors.lastname: Lusingu
authors.forename: Samwel
authors.initials: S
authors.lastname: Gesase
authors.forename: Salum
authors.initials: S
authors.lastname: Msham
authors.forename: Filbert
authors.initials: F
authors.lastname: Francis
authors.forename: Martha
authors.initials: M
authors.lastname: Lemnge
authors.forename: Misago
authors.initials: M
authors.lastname: Seth
authors.forename: Samwel
authors.initials: S
authors.lastname: Sembuche
authors.forename: Acleus
authors.initials: A
authors.lastname: Rutta
authors.forename: Daniel
authors.initials: D
authors.lastname: Minja
authors.forename: Method D
authors.initials: MD
authors.lastname: Segeja
authors.forename: Samuel
authors.initials: S
authors.lastname: Bosomprah
authors.forename: Simon
authors.initials: S
authors.lastname: Cousens
authors.forename: Ramadhani
authors.initials: R
authors.lastname: Noor
authors.forename: Roma
authors.initials: R
authors.lastname: Chilengi
authors.forename: Pierre
authors.initials: P
authors.lastname: Druilhe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology*; D002675:Child, Preschool; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D017325:Hepatitis B Vaccines; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D007279:Injections, Subcutaneous; D008213:Lymphocyte Activation / Q000276:immunology; D017780:Malaria Vaccines / Q000009:adverse effects* / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology* / Q000517:prevention & control; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D010963:Plasmodium falciparum / Q000187:drug effects / Q000276:immunology; D013636:Tanzania; D014614:Vaccines, Synthetic / Q000009:adverse effects* / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; C075654:Engerix-B; D017325:Hepatitis B Vaccines; C506685:MSP3 protein, Plasmodium falciparum (181-276); D017780:Malaria Vaccines; D010446:Peptide Fragments; D014614:Vaccines, Synthetic