GLUtamate-Rich Protein (GLURP) as Long Synthetic Peptide, later known as GMZ1
In malaria endemic areas, children often recover after chemotherapy of drug-resistant Plasmodium falciparum malaria. This implies a synergy between drug treatment and acquired immunity. We have examined this hypothesis in Chamwino village, situated in an area of moderately intense transmission of P. falciparum in Tanzania.
205 uncomplicated malaria patients below five years of age were randomly allocated to treatment with either sulfadoxine-pyrimethamine (SP), amodiaquine (AQ), or co-artem (CoA) and followed for 28 days. Adequate clinical and parasitological response (ACPR) was seen in 73% and parasitological or clinical treatment failures (TF) in 27% of all children. TF was higher in children receiving SP (68%) and AQ (38%) and less for CoA (< 2%).
The prevalence (OR: 5.0; 95% CI: 2.5-9.9, p<0.0001) and levels (95% CI for differences in median: 0.0-6.9; p<0.0001) of GLURP-specific IgG were higher on day 0 in children with ACPR than in children with TF after adjustment for the effect of age. Similar differences were seen on day 14, and when the SP and AQ groups were considered separately. Finally, levels of GLURP-specific IgG correlated inversely with parasite density on day 0 (p=0.006). We did not observe any statistically significant differences between children with ACPR and TF in the prevalence or levels of IgG with specificity for a range of other P. falciaparum antigens (AMA-1, CSP, MSP-1, MSP-3, three PfEMP1-antigens, and VSA).
Our findings suggest that GLURP-specific IgG antibodies contribute to clearance of drug-treated infections and support the hypothesis that acquired immunity enhances the clinical efficacy of drug therapy.
The GLURP project was received in response to a European Malaria Vaccine Initiative (EMVI) now European Vaccine Initiative call in 1998.
A contract was signed in 2000 for the product development of GLURP and Merozoite Surface Protein 3 (MSP3) as Long Synthetic Peptides at Biopôle, Lausanne with Sedac Therapeutics, Lille.
In 2001, a contract was signed with Stichting Katholieke Universiteit, University Medical Centre of Nijmegen for a Phase I clinical trial sponsored by European Malaria Vaccine Initiative (now European Vaccine Initiative):
Assessment of the Safety of a Long Synthetic Peptide Derived from GLURP, A Plasmodium falciparum Merozoite Surface Antigen Targeted by Biologically Active Human Antibodies : An Open, Randomized, Two Adjuvants, Four Doses Safety And Immunogenicity Phase I Clinical Trial
The results are published in Vaccine 25 issue 15 (2007) 2930-2940
GMZ1 in the expression system Lactoccocus lactis
Based on results of the Phase Ia clinical trial of GLURP as LSP, it was decided to pursue GLURP as a recombinant L. lactis protein called GMZ1, and a contract was signed in 2004 with Henogen, Charleroi for the production of a clinical batch. At the Scientific Advisory Committee (SAC) Portfolio Review Meeting in Copenhagen in October 2006, SAC recommended that the development of GMZ1 be put on hold until the results of the GMZ2 (GMZ1 + MSP3) safety and preliminary immunogenicity were available. Subsequently it was decided that further clinical development of GMZ1 would not be necessary.
GLURP (later combined with MSP3 to become GMZ2) remains with Statens Serum Institut
During 2009, EMVI became a separate legal entity in its own right, registered in Germany and is now known as European Vaccine Initiative - EEIG. In 2009, EMVI, in collaboration with its partners, was successful in negotiating a five year contract with the European and Developing Countries' Clinical Trials Partnership (EDCTP), coordinated by the African Malaria Network Trust, for the funding of the project entitled “Fostering Research Capacity, Networking and Project Management through Phase I-IIb Clinical Trials of Candidate Malaria Vaccine GMZ2”. As the title suggests, the project involves Phase II clinical trials of GMZ2 at several African sites. As the mandate of EMVI was primarily to develop experimental malaria vaccines up to Phase II clinical evaluation, GMZ2 will remain with Statens Serum Institut. It is the sincere hope of EVI-EEIG that Statens Serum Institut will be able to commit the resources necessary to continue the highly successful work of EMVI in the development of this promising malaria vaccine candidate, and to make it available to Developing Countries if the EDCTP project is successful.