- RFP Year2019
- Awarded Amount$972,951
- Development StageAntigen Identification
- Collaboration PartnersEhime University, University at Buffalo, The State University of New York, PATH Malaria Vaccine Initiative
Introduction and Background of the Project
Malaria remains one of the leading causes of deaths in young African children. Tranformative tools are urgently needed to ensure global control, elimination and eventual eradication goals are met; our vaccine approach has the potential to serve as one such transformational tool. Building on recent advances in the identification of leading malaria vaccine targets and novel delivery platforms, this project seeks to develop a vaccine to induce immunity that blocks parasite transmission between humans and mosquitoes. We will evaluate the capacity of CoPoP, a novel liposomal delivery platform, to co-deliver Pfs230 and CSP, two lead malaria vaccine candidates, to block parasite transmission from human-to-mosquito and mosquito-to-human, respectively. The planned work will generate necessary evidence to support a go/no-go decision to advance the candidate vaccine to preclinical development.
・Evaluate CSP immune enhancement using CoPoP liposomes coupled with immunestimulants (called CoPoP adjuvant in short thereafter).
・Evaluate feasibility of co-delivery of Pfs230C1 and CSP with CoPoP adjuvant for enhanced functional immunogenicity and protective efficacy in preclinical models.
・Evaluate immunogenicity of selected formulations in a second animal species suitable for GLP toxicology studies; develop analytical assays and release specifications for drug substance and drug product.
We will first apply knowledge and experience obtained from Pfs230C1 formulated with CoPoP adjuvant to evaluate the potential of CoPoP adjuvant for enhancing immunogenicity of CSP. We will then evaluate the capacity of co-formulating CSP and Pfs230 with CoPoP adjuvant, and the immune enhancement by CoPoP adjuvant to both CSP and Pfs230. Antigen incorporation and the stability of antigen-CoPoP formulations will be optimized using biochemical and biophysical methods. The functional immunogenicity of the antigen-CoPoP formulation will be evaluated by established functional assays: the standard membrane-feeding assay (SMFA) for Pfs230 and an in vivo mouse transgenic parasite challenge model for CSP. Aiming to advance Pfs230-CSP-CoPoP vaccine candidate toward preclinical development, we will also conduct a pilot study in additional animal species in order to inform future design of GLP toxicology study, and will develop assays in order to inform future establishment of product release specifications.
How can your partnership (project) address global health challenges?
Despite the successful scale-up of multiple interventions, an estimated 219 million cases and an estimated 435,000 malaria deaths occurred worldwide in 2017, according to the World Health Organization World Malaria Report. Achieving global burden reduction and regional elimination goals will require both more effective use of existing tools, and the development, introduction and scale-up of transformative new tools. Our vaccine approach has the potential to serve as one such transformational tool by contributing to burden reduction (by reducing clinical cases/deaths) and to regional elimination (by reducing the local reservoir of infected mosquitoes).
If proven to be safe and immunogenic in human volunteers, and with a line-of-sight to scalable low-cost manufacture, the CoPoP platform has the potential to be applied to global health needs beyond malaria.
What sort of innovation are you bringing in your project?
The project will employ a novel delivery platform, CoPoP, to co-deliver two lead malaria vaccine candidates target to sequential parasite development stages.
Role and Responsibility of Each Partner
PATH: For nearly 20 years, PATH has funded, coordinated, and applied scientific, technical, and managerial skills to a portfolio of malaria vaccine development projects conducted by partners in industry, government, and academia. PATH will serve as Project Lead for this project and will provide project management support, contribute recombinant proteins Pfs230C1 and CSP, and coordinate the design and execution of in vivo studies and immune assays.
SUNY: The State University of New York (SUNY) is the largest comprehensive university system in the United States and comprises 64 campuses, serving 1.4 million students. SUNY Buffalo, founded in 1846, is its flagship research university. SUNY is the inventor of the CoPoP technology and will conduct studies to optimize CoPoP adjuvant composition and formulation, perform analyticals on CoPoP adjuvant, prepare CoPoP adjuvant for in vivo studies, and conduct cellular assays.
Ehime University: The Ehime University team brings in considerable experience in basic research on malaria and tool development in vaccine candidate selection including sporozoite invasion in the host, and transmission-blocking vaccine target evaluations. For this project Ehime University will focus on evaluating immunogenicity and in vitro/in vivo function of the vaccine candidates in mice and rabbits.
Others (including references if necessary)
・WHO Global Techincal Strategy for Malaria 2016-2030. https://www.who.int/malaria/publications/atoz/9789241564991/en/
・WHO World Malaria Report 2018. https://www.who.int/malaria/publications/world-malaria-report-2018/en/
・Lee SM, Wu CK, Plieskatt CL et al, N-Terminal Pfs230 Domain Produced in Baculovirus as a Biological Active Transmission-Blocking Vaccine Candidate. Clin Vaccine Immunol. (2017) 24:e00140-7.
・Huang WC, Deng B, Lin C et al, A malaria vaccine adjuvant based recombinant antigen binding to liposomes. Nat.Nanotechnol. (2018) 13:1174-82.