title: Comparison of the immune responses induced by soluble and particulate Plasmodium vivax circumsporozoite vaccine candidates formulated in AS01 in rhesus macaques.
abstract: We have designed a pre-erythrocytic vaccine candidate based on the Plasmodium vivax circumsporozoite (CSV) protein, which includes its N- and C-terminal parts and a truncated region containing repeat sequences from both the VK210 and the VK247 P. vivax subtypes. Two versions of this vaccine candidate were made: a soluble recombinant protein expressed in Escherichia coli, designated VMP001 and a particulate antigen expressed in Saccharomyces cerevisiae, designated CSV-S,S. The latter is composed of CSV-S, a fusion protein between VMP001 and hepatitis B surface antigen (HBsAg), and free HBsAg co-expressed in yeast and self-assembling into mixed particles. Both antigen versions, adjuvanted with AS01, were shown to be immunogenic in rhesus monkeys. CSV-S,S/AS01 induced higher levels of VMP001-specific antibodies than did VMP001/AS01. Antibody responses against the N- and C-terminal regions of CSV and the VK210 repeat motif were of a similar magnitude following immunization with either the soluble or the particulate antigen. However, antibodies against the AGDR region, a potentially protective B cell epitope, were only detected after immunization with CSV-S,S. Analysis of the induced CD4(+) T cells highlighted different cytokine profiles depending on the antigen form. These results warrant further clinical evaluation of these two vaccine candidates to assess the added value of a particulate versus soluble form of CSV, in terms of both immunogenicity and protective efficacy.
authors.affiliation: GlaxoSmithKline Vaccines, Rixensart, Belgium. Electronic address: yannick.f.vanloubbeeck@gsk.com.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Vanloubbeeck
authors.forename: Sathit
authors.initials: S
authors.lastname: Pichyangkul
authors.forename: Babak
authors.initials: B
authors.lastname: Bayat
authors.forename: Kosol
authors.initials: K
authors.lastname: Yongvanitchit
authors.forename: Jason W
authors.initials: JW
authors.lastname: Bennett
authors.forename: Jetsumon
authors.initials: J
authors.lastname: Sattabongkot
authors.forename: Kurt
authors.initials: K
authors.lastname: Schaecher
authors.forename: Christian F
authors.initials: CF
authors.lastname: Ockenhouse
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: Anjali
authors.initials: A
authors.lastname: Yadava
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D015870:Gene Expression; D008253:Macaca mulatta; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D010966:Plasmodium vivax / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D016207:Cytokines; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D058425:Vaccines, Virus-Like Particle; C041595:circumsporozoite protein, Protozoan
keywords: AS01; BSA; CS; CSV; CSV-S,S; HBsAg; IFA; Immune response; Malaria; P.vivax circumsporozoite protein; PBMC; Plasmodium vivax; VMP001; bovine serum albumin; circumsporozoite; hepatitis B surface antigen; immunofluorescence assay; peripheral blood mononuclear cells