Research programs
Also referred to as translational programs, these are typically multi-year, multi-million dollar projects for which preclinical immunogenicity/efficacy testing has been completed and the commitment to clinical testing has been made. Most new programs coming into MVI enter as preclinical feasibility studies and, of those, a limited number subsequently advance to full portfolio, translational programs on a clinical track. This stage of development spans from preclinical studies through Phase 1 to Phase 2 studies.
Crucell adenovirus-based malaria vaccine candidate
Project Name: Crucell Holland Ltd. Ad35.CS/Ad26.CS Prime Boost
Partner: Crucell N.V.
Development stage: Preclinical; cGMP manufacturing
Platform: Replication-incompetent, recombinant human adenovirus serotype 35 and 26 vectors expressing P. falciparum gene encoding the circumsporozoite (CS) surface antigen
Antigen: Full-length CS gene
Adjuvant: N/A
Recent events: Completed release of Ad26.CS.01 Master Virus Seed and manufacture of Ad26.CS.01 drug substance (clinical trial material). Stability of Ad35.CS.01 drug product continues.
Project Initiation: October 2007
Project End-date: Current agreement with Crucell continues through July 2012. There is no project end-date identified for the clinical trial portion of the project.
Biological rationale: While recombinant adenoviruses are potent inducers of cell-mediated immunity (CMI) to heterologous antigens, the ability to boost immune responses is severely impaired by vector immunity induced following the primary immunization. Prime boost regimens, in which common antigens are delivered by different adenovirus serotypes, appear to circumvent this restriction and therefore hold significant promise for vaccine development using this delivery platform. Preclinical studies for assessment of the humoral and cellular responses to the prime boost of Ad35.CS.01/Ad26.CS.01 were completed in December 2008. The prime boost regimen was studied in mice with a group of 6-8 week old BALB/c mice immunized intramuscularly with Ad35.CS.01 (prime) at a dose of 1x109 vp followed by a boost with Ad26.CS.01 at a dose of 1x1010 vp. Significant IFN-g responses were measured by means of ELISPOT in groups of mice. Analysis of the CS antibody responses by ELISA showed that Ad35.CS.01/Ad26.CS.01 (prime boost) regimen-induced antibody responses that were significantly higher than responses induced by Ad35.CS.01/Ad26.Empty (prime only). Additional analysis of the antibody responses using immunofluorescence assay (IFA) on sera samples from Ad35.CS.01/Ad26.CS.01 groups of mice showed positive, indicating that antibodies induced by the prime boost regimen were able to bind to P. falciparum sporozoites. Poole sera from naïve mice were negative.
Read project fact sheet (34 KB PDF)
LaTrobe/QIMR (MSP2)
Project Name: LaTrobe merozoite surface protein 2 combination 1 (3D7:FC27)/ISA720
Main Partner: LaTrobe University
Additional Partners: CSL Limited; Queensland Institute of Medical Research (QIMR); Q-Pharm Pty Limited; CNS; Walter and Eliza Hall Institute of Medical Research (WEHI)
Development Stage: Early-stage clinical development
Platform: Recombinant protein, expressed in E. coli
Antigen: MSP2 is a ~28kDa protein that is anchored in the membrane of the merozoite by a C-terminal glycosylphosphatidyl-inositol moiety. Two sequences, representative of the two allelic families (3D7 and FC27), have been developed.
Adjuvant: Montanide ISA720 water-in-oil emulsion (SEPPIC, non-proprietary)
Recent events: N/A
Project initiation: January 2002
Project end date: December 2008
Biological rationale: MSP2 (the 3D7 allelic family) was a component of the Combination B candidate vaccine, which, in a Phase 1/2b trial in Papua New Guinea, reduced parasite densities in vaccinated children five to nine years old. Over a 12-month follow-up of the trial cohort, there was a higher incidence of morbidity associated with Plasmodium (P.) falciparum infections of the MSP2-FC27 allelic family in the group that received Combination B, indicating that activity of the Combination B candidate vaccine appeared to be at least partially due to the MSP2 (3D7) component of the vaccine. P. falciparum infections induce antibodies to MSP2, and the majority of individuals living in regions where there is intense transmission of P. falciparum develop high titers of anti-MSP2 antibodies by five years of age. Immunization of mice with MSP2 peptides has partially protected mice against challenge with virulent rodent parasite. Antibodies to MSP2 have been reported to block merozoite invasion in vitro. Several sero-epidemiological studies have shown an association between antibody responses to MSP2 and resistance to infection or disease (Polley SD, Conway DJ, Cavanagh DR, et al. 2006).
Sanaria PfSPZ
Project Name: Sanaria Inc. Plasmodium falciparum sporozoites
Main Partner: Sanaria Inc.
Additional Partners: US Navy Medical Research Center; Center for Vaccine Development, University of Maryland
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
Recent events: Clinical development plan meeting held July 21, 2008
Project initiation: October 2006
Project end date: December 2009
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.
Read project fact sheet (34 KB PDF)
