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. Of the programs that MVI currently supports, only GlaxoSmithKline Vaccines' RTS,S is considered a vaccine candidate.
GSK RTS,S AS01
Name: GlaxoSmithKline (GSK) RTS,S AS01.
Development stage: Phase 3 clinical trials completed.
Main partner: GlaxoSmithKline (GSK).
Additional partners: 11 African research centers/trial sites.
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 protein and the hepatitis B surface antigen (HBsAg).
- AS02: proprietary oil-in-water emulsion formulated with MPL® and Stimulon® QS21 immunostimulants.
- AS01: liposome formulation with MPL® and QS21 immunostimulants.
Project initiation: October 2005.
Project end date: Ongoing.
Biological rationale: The development of a malaria vaccine that targets the pre-erythrocytic stages of Plasmodium 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.