Project Title

Multi-site field trial of the FUJIFILM SILVAMP TB LAM Ⅱ including the diagnostic accuracy of a urine concentration device

Collaboration

Partners

1. Stop TB Partnership (Switzerland)

2. FUJIFILM Corporation (Japan)

3. Liverpool School of Tropical Medicine (LSTM) (UK)

4. Center for Health Promotion and Research (CHPR) (Cameroon)

5. Friends for International TB Relief (FIT) (Germany)

6. Zankli Research Centre, Bingham University Nigeria (ZRC) (Nigeria)

Disease

Tuberculosis

Intervention

Diagnostics

Stage

Product Validation

Awarded Amount

JPY 390,000,000 (USD 2.6 million)

Status

Continued project

Summary

[Project objective]

The primary objective of the project is to provide evidence on the performance of Fujifilm's redesigned SILVAMP TB LAM II assay as well as a urine concentration device (UCD) which is expected to further increase sensitivity especially in HIV-negative individuals to obtain a WHO policy recommendation with strengthened evidence based on the operationalization, costing and feasibility studies to be conducted on this project.

[Project design]

The project team will prospectively evaluate the performance of the SILVAMP TB LAM Ⅱ assay as well as a urine concentration device across multiple sites in Cameroon, Nigeria and Vietnam. The project team will evaluate test performance among PLHIV and HIV-negative adults as well as children irrespective of HIV co-infection. Operationalization, costing and feasibility of the assay will also be addressed.

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/246/en

Project Title

Evaluation of the Safety and Immunogenicity of the cGMP LmCen-/- Vaccine in Phase I Clinical Trials

Collaboration

Partners

1. The Ohio State University (USA)

2. Nagasaki University (Japan)

Disease

Leishmaniasis

Intervention

Vaccines

Stage

Clinical Phase I

Awarded Amount

JPY 681,063,113 (USD 4.5 million)

Status

Continued project

Summary

[Project objective]

Objective 1: Conduct a Phase I clinical trial to evaluate the safety and immunogenicity of the LmCen-/- vaccine in healthy volunteers in Brazil (New World)

Objective 2: Conduct a Phase I clinical trial to evaluate the safety and immunogenicity of the LmCen-/- vaccine in healthy volunteers in Kenya (Old World)

[Project design]

This project is a continuation of the GHIT-funded project G2018-201 to advance clinical development of the LmCen-/- vaccine. During the previous funding period, the project team successfully accomplished the goals of the project by:

1) Validate the safety and efficacy of a GLP-grade LmCen-/- vaccine produced by Gennova Biopharmaceuticals under cGMP conditions using preclinical animal models,

2) Produce a GMP master cell bank (MCB) and a GMP working cell bank (WCB) of LmCen-/- parasites,

3) Establish cGMP manufacturing of the LmCen-/- vaccine,

4) Complete preclinical toxicology studies in accordance with regulatory guidelines using a GLP LmCen-/- vaccine produced from an engineering run of the cGMP cell bank, and

5) Finalize the IND package for the LmCen-/- product for submission to regulatory authorities.

In the current project, the project team proposes to evaluate the safety of the LmCen-/- vaccine in healthy volunteers living in leishmaniasis-endemic countries, Brazil and Kenya, where other factors such as subclinical nutritional deficiencies and co-infections, such as diarrhea, malaria, Chagas disease (in Brazil) and helminth infections, are common and have been documented to impact vaccine safety and immunogenicity.

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/247/en 

Project Title

Strongyloides stercoralis Rapid Test Plus (SsRT+): A new rapid diagnostic test with improved ease of use to support WHO strongyloidiasis control programs.

Collaboration

Partners

1. Drugs & Diagnostics for Tropical Diseases (DDTD) (USA)

2. Medical & Biological Laboratories Co., Ltd. (MBL) (Japan)

3. IRCCS Sacro Cuore Don Calabria Hospital (Italy)

4. QIMR Berghofer Medical Research Institute (Australia)

5. Fundacion Mundo Sano (Spain)

6. Big Eye Diagnostics, Inc. (BEDx) (USA)

Disease

Strongyloidiasis (Soil-transmitted helminth)

Intervention

Diagnostic

Stage

Product Design

Awarded Amount

JPY 566,596,199 (USD 3.8 million)

Status

New

Summary

[Project objective]

The overarching goal of this project is to deliver an easy-to-use, low-cost point-of-care test to detect S. stercoralis infection. Our new test, termed S. stercoralis Rapid Test Plus (SsRT+), will be an improved version of SsRapid, which was developed and validated by our Consultant, Prof. R. Noordin, and has been shown to be 80-97% sensitive and 90-100% specific in a series of laboratory and field studies. A first SsRT+ prototype has already been generated, which showed diagnostic performance comparable to, or better than, SsRapid. SsRT+ will be fully optimized in this project to meet all key criteria of the new TPP for S. stercoralis diagnostics.

[Project design]

Objective-1: This first activity aims to review the optimal use case(s) and define the key experimental data to be generated with SsRT+ to align with the WHO strongyloidiasis control programs. We will also finalize the study plans for the field evaluations in Australia and Argentina and complete a business/commercialization plan.

Objective-2: Having access to high-quality antigens and positive control antibodies is key for efficient test development, optimization, and manufacturing under ISO-13485:2016 standards. As for all our other GHIT Fund projects, MBL will be entrusted with the production of high-quality recombinant NIE and IgG4-anti-NIE. 

Objective-3: The SsRT+ prototype available at the outset of G2025-101 will be fully optimized, according to all key criteria listed in the TPP for S. stercoralis diagnostics, including sensitivity, specificity, time to result, result stability, reproducibility (CV values), and cost. Since the precursor of SsRT+, SsRapid, already meets most of the TPP criteria, we consider this a very realistic objective.

Objective-4: Prof. R. Noordin of Universiti Kebangsaan Malaysia (UKM), who has developed and validated SsRapid in numerous laboratory and field studies, and Prof. D. Buonfrate of IRCCS Sacro Cuore Don Calabria Hospital, who has previously run an in-depth diagnostic accuracy study involving SsRapid, will independently evaluate the diagnostic performance of SsRT+ to demonstrate that it complies with the TPP and is not inferior to SsRapid.

Objective-5: Once validated for TPP-compliant performance in the laboratory, SsRT+ will be evaluated in two field studies in Australia and Argentina, conducted by the groups of Prof. D. Gray of QIMR Berghofer and Prof. A. Krolewiecki of Mundo Sano, respectively.

Objective-6: An ISO-13485:2016 compliant automated manufacturing process commensurate with the anticipated demand will be developed by DDTD, modeled on the one we successfully put in place for our Onchocerciasis rapid test in the GHIT Fund project G2023-111, and subsequently validated by BEDx through production of several pilot lots and quantification of inter-lot consistency.

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/248/en 

Project Title

Development of Ultrasensitive and Robust Malaria Rapid Diagnostic Tests Using de novo Designed Antigen Binders

Collaboration

Partners

1. Ehime University (Japan)

2. Institute of Tropical Medicine (NEKKEN) Nagasaki University (Japan)

3. Universiti Malaysia Sabah (Malaysia)

Disease

Malaria

Intervention

Diagnostics

Stage

Concept Development

Awarded Amount

JPY 99,670,808 (USD 0.6 million)

Status

New

Summary

[Project objective]

Current malaria Lateral Flow Assays (LFAs) use antibodies as their capture and detection reagents. The limited sensitivity of LFAs in part reflects the relativity modest affinities of typical antibodies for their target proteins. In addition, the identification of antibodies that target related proteins with high specificity is time-consuming and uncertain of success. A technology that replaces monoclonal antibodies could thus have a transformative impact on the development of new diagnostics. We propose to develop novel protein-based affinity reagents that enable the creation of rapid diagnostic tests (RDTs) that diagnose infection with Plasmodium falciparum, non-falciparum malaria parasites, and the emerging pathogen Plasmodium knowlesi with sensitivities that considerably exceed existing alternatives. Our work will result in affinity reagents that integrate directly into the existing infrastructure for the creation of LFAs, the technology used in rapid COVID tests. The products of this project can thus be rapidly scaled to impact malaria treatment worldwide. As part of this project, we will validate our approach using clinical samples. If successful, the diagnostics resulting from our collaboration will possess enhanced sensitivity, greater shelf stability, lower cost, and the elimination of test failure due to parasite mutations, four improvements that have been identified as critically important by the World Health Organization (WHO) for the management of malaria. Success in this project will establish a general-purpose platform for the rapid development of highly sensitive diagnostic assays. In addition to its impact on malaria diagnosis and treatment, this project will thus provide proof-of-concept for a novel platform technology enabling the development of rapidly scalable diagnostics for novel infectious diseases. Our overall goals are thus to develop new protein-based affinity reagents that can improve the sensitivity of malaria LFAs, and to extend malaria LFAs to include diagnosis of infection with P. knowlesi.

[Project design]

Our overall strategy is to replace the antibodies that are used in conventional LFAs with computationally designed binders based on the monobody scaffold. The nanomolar (nM) affinities of most antibodies limit the sensitivity of LFAs. To circumvent this limitation, we will use de novo protein design to identify numerous monobody binders for a target malaria antigen of interest. We will then link monobodies together to generate bivalent binders for the malaria antigens. This strategy makes use of the well-known principle of avidity, in which linear improvements in binding energy yield exponential improvements in dissociation constants: both empirical evidence and simple calculations indicate that combining monobody binders with 10-100 nM KD values should yield multivalent binders with KD values in the pM regime. Importantly, this strategy is made possible by the unique ability of computational design to deliberately target multiple, distinct sites on the target protein. We will quantify the binding affinities and cross-reactivity of bivalent monobodies and confirm that they possess the properties required for use in an LFA. Finally, we will assess the performance of the resulting capture and detection reagents in prototype LFAs.

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/249/en