• Vaccine Name: P. falciparum vaccine Combination B
• Target Pathogen: Plasmodium spp.
• Target Disease: Malaria
• Tradename: Combination B
• Vaccine Ontology ID: VO_0000740
• Type: Subunit vaccine
• Antigen: The vaccine Combination B contains three recombinant asexual blood-stage Plasmodium falciparum proteins: merozoite surface protein (MSP) 1, MSP2 and ring-infected erythrocyte surface antigen (RESA) (Genton et al., 2003).
• RESA gene engineering:
  • Type: Recombinant protein preparation
  • Description: The vaccine Combination B contains peptides from the ring-infected erythrocyte surface antigen (RESA) (Genton et al., 2003).
  • Detailed Gene Information: Click Here.
• MSP-1 from P. falciparum gene engineering:
  • Type: Recombinant protein preparation
  • Description: The vaccine Combination B contains MSP1 peptides (Genton et al., 2003).
  • Detailed Gene Information: Click Here.
• Adjuvant:
  • Adjuvant name:
  • VO adjuvant ID: VO_0001268
  • Description: Montanide ISA 720. It is an oil composition containing a natural metabolizable oil and a highly refined emulsifier from the mannide mono-oleate family (Genton et al., 2003).
• Preparation: Combination B is a malaria vaccine that comprises recombinant P falciparum blood-stage proteins MSP1, MSP2 and RESA, formulated with the adjuvant Montanide ISA 720 (Genton et al., 2003a). The three vaccine candidate antigens were produced by recombinant DNA technology. All three antigens were expressed in Escherichia coli with histidine tags to facilitate purification by nickel chelate chromatography. Two of the antigens, 190LCS.T3 (Ro 45-2067) and Ag1624 (Ro 46-2924), corresponded to parts of the well-characterized merozoite surface proteins MSP1 and MSP2, respectively. The MSP1 antigen was the 190L fragment from the K1 parasite line, comprising the relatively conserved blocks 3 & 4 of MSP1 fused with a universal T cell epitope derived from the circumsporozoite protein of P. falciparum. The MSP2 antigen corresponded to the near full-length MSP2 sequence of the 3D7 cloned line. Ag1505H (Ro 45-2164) consisted of the C-terminal 70% of RESA of the FCQ-27/PNG parasite line. All three antigens were supplied in separate vials at a concentration of 160 μg/ml of saline-Montanide ISA720 emulsion. Prior to use the three formulations were mixed and diluted with additional emulsion to give a dose of 15 μg of each antigen in a total volume of 0.55 ml (Genton et al., 2003).
• Description: The "Combination B" vaccine resulted from a collaborative effort by the Papua New Guinea Institute for Medical Research along with the Australian Cooperative Research Center for Vaccine Technology in Queensland, The Walter and Eliza Hall Research Institute and the Swiss Tropical Institute (Girard et al., 2007). This vaccine has led to a considerable reduction of parasite density in the immunized children.

Human Response

• Host Strain: Papua New Guinean children
• Vaccination Protocol: To insure safety, the enrolment and immunisations were done sequentially, with 10 days observation between each sub-cohort. It was started with one block (3 No SP+vaccine, 3 No SP+placebo, 3 SP+vaccine, 3 SP+placebo) of the older age group, then the remaining four blocks (12 No SP+vaccine, 12 No SP+placebo, 12 SP+vaccine, 12 SP+placebo) of this stratum, then one block of the younger age group, and then the remaining four blocks of this stratum. Children were given either SP or a sugar tablet (indistinguishable tablets provided by Hoffman La-Roche). During Week 0 they were injected i.m. in the left lateral thigh with the vaccine or placebo. Four weeks after the first injection, they received a second injection i.m. in the right lateral thigh (Genton et al., 2003).
• Immune Response: The vaccine induced significant antibody responses to all three antigens but triggered an IFN-γ response to MSP1 only. At Week 12, the IFN-γ response to MSP1 was substantially higher in the vaccine group where No SP had been given (Genton et al., 2003)
• Side Effects: No serious or severe AEs occurred. Moderate AEs were seen in 3% of the vaccine and 3% of the placebo recipients after first injection and in 12 and 10% after second injection (Genton et al., 2003).
• Description: This is a phase I-IIb double-blind randomised placebo-controlled trial was undertaken in 120 children aged 5-9 years.