title: Immunogenicity of dimorphic and C-terminal fragments of Plasmodium falciparum MSP2 formulated with different adjuvants in mice.
abstract: BACKGROUND
  Plasmodium falciparum MSP2 is a blood stage protein that is associated with protection against malaria. It was shown that the MSP2 dimorphic (D) and constant (C) regions were well recognized by immune human antibodies, and were characterized by major conserved epitopes in different endemic areas and age groups. These Abs recognized merozoite-derived proteins in WB and IFA. Here, the goal was to determine in mice the immunogenicity of the two allelic MSP2 D and C domains formulated with different adjuvants, for their possible use in future clinical studies.
  
  
  METHODS
  Female A/J, C3H, and ICR mice were immunized subcutaneously 3 times at 3-week interval with a mixture of allelic and conserved MSP2 long synthetic peptides formulated with different adjuvants. One week after the third injection, sera from each group were obtained and stored at -20°C for subsequent testing.
  
  
  RESULTS
  Both domains of the two MSP2 families are immunogenic and the fine specificity and intensity of the Ab responses are dependent on mouse strains and adjuvants. The major epitopes were restricted to the 20-mer peptide sequences comprising the last 8aa of D and first 12aa of C of the two allelic families and the first 20aa of the C region, this for most strains and adjuvants. Strong immune responses were associated with GLA-SE adjuvant and its combination with other TLR agonists (CpG or GDQ) compared to alhydrogel and Montanide. Further, the elicited Abs were also capable of recognizing Plasmodium-derived MSP2 and inhibiting parasite growth in ADCI.
  
  
  CONCLUSIONS
  The data provide a valuable opportunity to evaluate in mice different adjuvant and antigen formulations of a candidate vaccine containing both MSP2 D and C fragments. The formulations with GLA-SE seem to be a promising option to be compared with the alhydrogel one in human clinical trials.
authors.affiliation: Department of Biochemistry, University of Lausanne, Ch des Boveresses 155, Epalinges, Switzerland(1). Electronic address: balamsira@yahoo.fr.
authors.forename: Saidou
authors.initials: S
authors.lastname: Balam
authors.affiliation: Pasteur Institut, Paris, France. Electronic address: ajafarshad@gmail.com.
authors.forename: Ali
authors.initials: A
authors.lastname: Jafarshad
authors.affiliation: Department of Biochemistry, University of Lausanne, Ch des Boveresses 155, Epalinges, Switzerland(1). Electronic address: Ekaterini.Servi@unil.ch.
authors.forename: Catherine
authors.initials: C
authors.lastname: Servis
authors.affiliation: Department of Biochemistry, University of Lausanne, Ch des Boveresses 155, Epalinges, Switzerland(1). Electronic address: geraldine.frank@unil.ch.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Frank
authors.affiliation: IDRI, Seattle, USA. Electronic address: Steven.Reed@idri.org.
authors.forename: Steve
authors.initials: S
authors.lastname: Reed
authors.affiliation: Department of Biochemistry, University of Lausanne, Ch des Boveresses 155, Epalinges, Switzerland(1). Electronic address: pinkr@mail.com.
authors.forename: Richard
authors.initials: R
authors.lastname: Pink
authors.affiliation: Pasteur Institut, Paris, France. Electronic address: druilhe@vac4all.org.
authors.forename: Pierre
authors.initials: P
authors.lastname: Druilhe
authors.affiliation: Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. Electronic address: francois.spertini@chuv.ch.
authors.forename: François
authors.initials: F
authors.lastname: Spertini
authors.affiliation: Department of Biochemistry, University of Lausanne, Ch des Boveresses 155, Epalinges, Switzerland(1). Electronic address: giampietro.corradin@unil.ch.
authors.forename: Giampietro
authors.initials: G
authors.lastname: Corradin
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood*; D000953:Antigens, Protozoan / Q000276:immunology*; D002478:Cells, Cultured; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology; D005260:Female; D005960:Glucosides / Q000737:chemistry; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008050:Lipid A / Q000737:chemistry; D017780:Malaria Vaccines / Q000276:immunology*; D008809:Mice, Inbred C3H; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D009000:Monocytes / Q000469:parasitology; D010963:Plasmodium falciparum / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology*; D051193:Toll-Like Receptors / Q000819:agonists; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000939:Epitopes; D005960:Glucosides; D007074:Immunoglobulin G; D008050:Lipid A; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D051193:Toll-Like Receptors; D014614:Vaccines, Synthetic; C000608161:glucopyranosyl lipid-A; C065974:merozoite surface protein 2, Plasmodium
keywords: Adjuvant; Constant region; Dimorphic region; Immunogenicity; MSP2; P. falciparum