Preclinical development of malaria transmission-blocking vaccine candidate Pfs230D1+ formulated with SA-1 adjuvant
Project Completed
Please click to see the final report.

Introduction and Background of the Project


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.


WHO World Malaria Report 2019.


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.

Final Report

1. Project objective

The three objectives in this project include:

  • Manufacture and release of Pfs230D1+ antigen and SA-1 adjuvant to support a nonclinical toxicology study.
  • Submission of a Pre-IND meeting package to the United States Food and Drug Administration (US FDA) to consult with the agency on the plan for preclinical safety testing and our proposed Phase 1 clinical trial design.
  • Conduct an IND-enabling GLP-compliant safety testing of the Pfs230D1+/SA-1 formulation.


2. Project design

For manufacture of the Pfs230D1+ antigen and SA-1 adjuvant, the process was tech-transferred from a research organization to a contract development and manufacturing organization (CDMO), where the antigen and the adjuvant were manufactured and released per pre-determined specifications.

  • The US FDA’s concurrence was obtained on the manufacture processes and release specifications for Pfs230D1+ antigen and for SA-1 adjuvant, and the design of the IND-enabling GLP safety testing of the Pfs230D1+/SA-1 to support the proposed first-in-human (FIH) study.
  • The IND-enabling safety testing on Pfs230D1+/SA-1 was conducted in compliance with GLP regulations.


3. Results, lessons learned

All three milestones were achieved as described below:

Milestone 1.  Pfs230D1+ (engineering run quality) and formulated SA-1 adjuvant (cGMP quality) produced and released. The engineering lot of the Pfs230D1+ antigen was successfully manufactured, vialed, and released as per predetermined specifications. The antigen was shown to be stable under accelerated stressed conditions of temperatures or after multiple freeze-thawing cycles, as well as after long-term storage at below -65°C, per data collected up to the end of this project (12 months). The functional immunogenicity of the engineering lot of Pfs230D1+ was confirmed by induction of transmission reducing antibodies in mice.
The engineering lot and a GMP lot of SA-1 were also successfully manufactured per pre-determined specifications. The adjuvant was stable under accelerated conditions, as well as after long-term storage, per data collected up to the completion of this project. 
Pfs230D1+ and SA-1 will be formulated by mixing the two prior to vaccination. The formulated vaccine was shown to be stable up to 24-hours of storage at 2-8°C or 25°C which was adequate to support the pharmacy manipulations and vaccine delivery for the planned non-clinical and clinical studies.

Milestone 2. Regulatory guidance on preclinical safety testing received from US FDA. Two consultations were conducted with the US FDA. The first one was a Type C meeting where the US FDA reviewed the results of toxicology studies conducted with the SA-1 adjuvant alone. The agency stated no concern regarding SA-1 based on the results from these studies. The second one was a Pre-IND meeting where the US FDA reviewed the manufacturing processes and the data to date and concurred with manufacture release specifications for the antigen and the adjuvant. The agency also concurred with the design of the GLP toxicology study on Pfs230D1+/SA-1, and the design of the planned first-in-human (FIH) study.  

Milestone 3. The IND-enabling GLP toxicology study completed. An IND-enabling GLP toxicology study was conducted in rats where animals received a total of four doses of Pfs230D1+/SA-1, control article (saline), Pfs230D1+ alone, or SA-1 alone. All animals survived until the scheduled necropsy. The Pfs230D1+/SA-1 was well-tolerated, and there was no safety issue.