Vaccine candidates
MVI maintains a vaccine project portfolio with a diversity of preclinical, early clinical, and at least one advanced clinical project. The portfolio is continuously assessed through a range of internal structures and processes. Each project is managed by a cross-functional team that continually analyzes the project’s progress, while a portfolio management committee ensures transparent decision-making.
We also make routine use of external experts. Technical advisory groups employ a carefully developed review system that allows only the strongest vaccine candidates to move forward. Continued support of a project depends on whether the candidate meets a series of clearly defined milestones related to safety, efficacy, and suitability for mass production. Our vaccine candidates currently include the following:
GSK RTS,S AS01/AS02
Name: GlaxoSmithKline Biologicals (GSK) RTS,S AS01/AS02.
Development stage: Phase 2 trials; preparation for Phase 3.
Platform: The RTS,S antigen, produced in S. cerevisiae, consists of the two proteins RTS and S that intracellularly and spontaneously assemble into mixed polymeric particulate structures that are each estimated to contain, on average, 100 polypeptides.
Antigen: RTS,S (consists of sequences of the circumsporozoite (CS) protein and the hepatitis B surface antigen (HBsAg).
Adjuvant: AS02D/AS01E.
- AS02: proprietary oil-in-water emulsion formulated with MPL® and Stimulon® QS21 immunostimulants.
- AS01: liposome formulation with MPL® and QS21 immunostimulants.
Main partner: GlaxoSmithKline Biologicals.
Additional partners: Malaria Clinical Trials Alliance; 11 African clinical trial sites.
Recent events: Completion of Phase 2 program; preparations for Phase 3.
Project initiation: October 2005.
Project end date: October 2011.
Read project fact sheet (53 KB PDF)
Biological rationale: The development of a malaria vaccine that targets the pre-erythrocytic stages of Plasmodium (P.) falciparum is based on the assumption that the vaccine would elicit a strong neutralizing humoral immune response directed against surface-exposed sporozoite proteins. This antibody-mediated protection would be achieved either through opsonization and destruction of the invading parasites by macrophages, through the inhibition of a function that is essential for sporozoite invasion of the live, or both.
Additionally, because most free sporozoites persist in the bloodstream for less than 30 minutes and it’s likely that some parasites will have invaded liver cells within a few minutes following an infectious bite, an efficient pre-erythrocytic vaccine should also elicit Cell Mediated Immune (CMI) responses of the CD8+ and CD4+ Th1 type. The role of these T cells is to recognize infected liver cells through parasite-derived processed peptides exposed at the surface of infected hepatocytes in association with the major histocompatibility complexes (MHC) class I and class II. These effector T lymphocytes can either lyse infected liver cells or impede further intracellular parasite development through the localized secretion of appropriate cytokines. Ideally, both types of immune responses (humoral and cell-mediated) should be recalled following further vaccination or upon subsequent natural infection. The vaccine should therefore be capable of inducing appropriate subsets of memory T and B cells, specific for epitopes derived from parasite proteins.
ICGEB PvRII
Name: International Centre for Genetic Engineering and Biotechnology Plasmodium vivax Region II.
Development stage:
Platform: Recombinant protein expressed in E. coli and refolded from inclusion bodies.
Antigen: Blood-stage Duffy Binding Protein of P. vivax (PvDBP) is the obligate ligand for invasion into erythrocytes. Region II of this protein (PvRII) comprises the functional receptor-binding domain of PvDBP. PvRII contains around 350 amino acids, including 12 cysteines. A hexa-histidine tag was inserted into the C-terminal of the recombinant PvRII construct to aid purification.
Adjuvant: TBD.
Main partner: ICGEB, New Delhi, India.
Additional partners: TBD.
Recent events: N/A.
Project initiation: July 2001.
Project end date: Estimate Q4, 2008.
Read project fact sheet (35 KB PDF)
Biological rationale: For P. vivax malaria, the Duffy blood group antigen on the surface of erythrocytes has been shown to be the sole receptor for invasion. The interaction is mediated by PvRII, a region of the Duffy Binding Protein on the surface of P. vivax parasites. Naturally acquired antibodies against PvRII have been shown to block binding of PvDBP to erythrocytes in in vitro binding assays, and Duffy-negative human erythrocytes are completely resistant to invasion by P. vivax (Michon, et al. 2000). In addition, the simian parasite P. knowlesi has a Duffy Binding Protein (PkDBP), which contains a binding domain that is homologous to PvRII. Antibodies to the binding domain of PkDBP have been shown to block invasion of human erythrocytes by P. knowlesi. These observations, in addition to the fact that individuals residing in malaria-endemic areas acquire antibodies directed against the binding domains of PvDBP followed by exposure to P. vivax (Singh, et al. 2002), provide strong rationale for development of a vaccine based on PvRII.
Recombinant PvRII specifically binds Duffy-positive human erythrocytes in erythrocyte-binding assays. Rabbit serum raised against PvRII completely blocks binding of human erythrocytes to COS cells, expressing PvRII on their surface up to a dilution of 1:2,500. Naturally occurring antibodies directed against PvRII block binding completely only up to a dilution of 1:20 in similar binding assays (Yazdani 2004).
Sanaria Pf SPZ
Name: Sanaria Inc. Plasmodium falciparum sporozoites.
Development stage: Biodistribution study and preparation for Investigational New Drug (IND) ongoing.
Platform: Live attenuated sporozoites extracted from the salivary glands of irradiated P. falciparum-infected mosquitoes.
Antigen: Sporozoite and liver-stage complex.
Adjuvant: N/A.
Main partner: Sanaria Inc.
Additional partners: US Navy Medical Research Center; Center for Vaccine Development, University of Maryland.
Recent events: Clinical development plan meeting held July 21, 2008.
Project initiation: October 2006.
Project end date: December 2009.
Read project fact sheet (31 KB PDF)
Biological rationale: An estimated 5,000 to 10,000 irradiated sporozoites, delivered by the feeding of more than 1,000 irradiated, infected mosquitoes, protected volunteers from subsequent feeding of unirradiated, infected mosquitoes.
