Periodic Reporting for period 2 - MultiViVax (Development of Effective Vaccines against Multiple Lifecycle Stages of Plasmodium vivax malaria)
Reporting period: 2018-07-01 to 2019-12-31
MultiViVax aims to develop effective vaccines for P. vivax malaria, which will have massive impact in countries where the disease is prevalent. A highly effective vaccine against P. vivax will reduce the burden of morbidity and mortality associated with the disease. Additional impacts on public health in Europe and worldwide would be made by development and licensure of vaccines for military personnel and travellers.
We have laid out four objectives to enable us to address the critical bottlenecks in P. vivax vaccine development:
1. Establish a P. vivax CHMI model in Europe for the first time to facilitate better selection of effective vaccines and remove the current bottleneck for early-phase clinical testing.
2. Utilise the CHMI model to identify novel antigens associated with protective blood-stage immunity in humans by taking advantage of recent advances in immuno-screening and parasite RNASeq.
3. Progress existing vaccines targeting the current leading antigens for both the blood- and transmission-stages along the clinical development pipeline.
4. Develop novel transgenic parasites for use in assays, to overcome the current bottleneck in vaccine down-selection caused by the inability to culture P. vivax parasites.
Samples collected during the CHMI re-infection trials will also be used for parasite RNAseq and immuno-screening analysis. In preparation for these assays a P.vivax protein expression library is currently under development
The leading P. vivax transmission-blocking antigen has been evaluated in the form of two different vaccine candidates, which have been optimised and characterised preclinically. The leading preclinical candidate has undergone cGMP manufacture during 2019/2020 in preparation for Phase I clinical testing.
As part of this trial the functional impact of antibodies induced by vaccination will be assessed using a standard membrane feeding assay using a transgenic P. falciparum line. The generation of this transgenic parasite is underway and constructs are being generated while viability testing of the parasite is ongoing.
An in vitro culture is being established and growth inhibition assay (GIA) methodology using a P. knowlesi strain adapted to continuous growth in human red blood cells. Development of GIA methodology with wild-type and transgenic P. knowlesi parasite lines is now underway. These parasites will be used to test for GIA in the serum of vaccinees from the clinical trials.
MultiViVax has established governance with a Project Steering Committee, Independent Scientific Advisory Committee and Local Safety Committee to oversee the progression of work throughout the project.
If sufficiently effective, a vaccine will provide a key milestone towards malaria eradication.
Development of a CHMI model and in vitro assays will remove bottlenecks that have hindered P. vivax research and will be made available to others developing vaccines for P. vivax malaria. This will accelerate the clinical development and testing of a range of novel second-generation vaccine candidates in the future by establishing the first blood-stage and transmission-stage P. vivax CHMI models in Europe.
We will extend the CHMI model to induce acquired immunity against P. vivax blood-stage by re-infection of volunteers with homologous parasites. This will help us dissect the human immune response to identify P. vivax antigens associated with protection using the latest advances in protein expression, immunomonitoring and parasite RNAseq technologies, paired with assays using novel transgenic parasites in related human Plasmodium species.
The expansion of vaccine research achieved throughout the project will result in higher employment through academic research and the private sector and strengthen the growth of both academia and industry in Europe by increasing the competitive advantage and attractiveness as a location-of-choice to carry out advanced medical research. Opportunity for a malaria vaccines is divided into the public (population of malaria endemic countries) and private (military and travellers) markets, both of which are sensitive to the efficacy of the vaccine, its price and availability of public funding to subsidise its cost and support deployment.
During production of the transmission-blocking vaccine candidate we will produce single subunit vaccines, as opposed to the more traditional approach of attenuating or inactivating live organisms. We also use affinity processes which utilise non-toxic reagents. The process is therefore less environmentally harmful than other affinity chromatography techniques, which use a column containing cobalt or nickel ions.