Introduction and Background of the Project

Introduction

Malaria remains one of the leading causes of deaths in young African children. New 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. This proposal seeks support for the preclinical development of a vaccine candidate that blocks parasite transmission from human to mosquito.

Project objective

The goal of this proposal is to generate all the preclinical information necessary to advance a novel candidate Plasmodium falciparum (malaria) vaccine to the clinical testing stage. This transmission-blocking vaccine (TBV) incorporates an optimized immunogen, Pfs230D1+ formulated with novel TLR7 adjuvant (SA-1). At the end of the project, the partners will be ready for clinical phase manufacturing and the filing of an Investigational New Drug (IND) application to the US Food and Drug Administration (US FDA).

Project design

This project is a continuation of a GHIT Fund grant (T2016-207) in which the optimal region of the Pfs230 protein was identified for inclusion in a TBV. The current project includes the generation of the high-quality vaccine and adjuvant suitable for performance of definitive safety/toxicology studies. Contact with the US FDA will be made to assure that our plans are appropriate for testing of both a novel vaccine and adjuvant.

How can your partnership (project) address global health challenges?

Despite the successful scale-up of multiple interventions, an estimated 228 million cases and an estimated 405,000 malaria deaths occurred worldwide in 2018, according to the World Health Organization (World malaria report 2019). 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. Blocking the cycle of transmission from human to mosquito has been a long-term objective of malaria interventions. The vaccine described in this program has the potential to provide durable inhibition of transmission, thus advancing the goal of malaria elimination.

What sort of innovation are you bringing in your project?

This project employs both an optimized immunogen Pfs230D1+, which contains the key regions necessary for antibody mediated inhibition of P. falciparum transmission, and a novel TLR7 adjuvant (SA-1) to promote a potent and durable effect.

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 (Pfs230D1+), and coordinate the design and execution of in vivo studies and immune assays.  PATH will also oversee regulatory filings and communications. 

Ehime University: The Ehime University team brings considerable experience in malaria research, tool development, and transmission-blocking vaccine target evaluations. The Ehime team was a full partner in the earlier GHIT-funded project that identified the Pfs230D1+ immunogen. For the current project, Ehime University will focus on evaluating immunogenicity and in vitro/in vivo function of the vaccine candidates in mice and the testing of the Pfs230D1+ immunogen in SA-1 adjuvant.

Sumitomo Dainippon Pharma Co., Ltd.: Sumitomo Dainippon Pharma brings decades of research and development experience with a robust drug pipeline to the project. Sumitomo Dainippon Pharma will be responsible for the generation of SA-1 formulated adjuvant, including the generation of clinical grade product and assays to measure its stability. Sumitomo Dainippon Pharma will provide the information about SA-1 adjuvant alone to be available to the program for use in regulatory filings. 

Others (including references if necessary)

WHO Global Technical Strategy for Malaria 2016-2030. https://www.who.int/malaria/publications/atoz/9789241564991/en/

WHO World Malaria Report 2019.

https://www.who.int/malaria/publications/world-malaria-report-2019/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.

Tachibana M, Miura K, Takashima E, Morita M, Nagaoka H, Zhou L, Long CA, King CR, Torii M, Tsuboi T, Ishino T. Identification of domains within Pfs230 that elicit transmission blocking antibody responses. Vaccine. 2019 Mar 22;37(13):1799-1806.