Statens Serum Institut Initiates Phase2 Efficacy Trial for Standalone Multi-stage Malaria Vaccine Candidate 

Following two successful Phase 1 trials of a novel vaccine candidate containing Statens Serum Institut’s ProC6C protein together with Novavax’s Matrix-M™ adjuvant, the first patient has been dosed at Mali trial site.

Statens Serum Institut (SSI), today announced the initiation of a Phase 2 Clinical trial for its investigational malaria vaccine, which contains SSI’s ProC6C antigen and Novavax’s Matrix-M™ adjuvant. Developed and manufactured by SSI, under the support of the European & Developing Countries Clinical Trials Partnership (EDCTP2), this vaccine candidate was previously evaluated for safety and immunogenicity in healthy human adult volunteers in Burkina Faso and Mali. SSI will now measure the efficacy of the ability of ProC6C/Matrix-M vaccine to prevent infection through a Phase 2 challenge study conducted in adults aged 18-50 years.

  • ProC6C is a multi-stage malaria vaccine designed to reduce parasite transmission and prevent human infection.
  • Two Phase 1 trials of ProC6C administered with Matrix-M adjuvant demonstrated favorable safety and tolerability at all dose levels in healthy adults, as well as transmission-reducing activity
  •  A Phase 2 controlled human malaria infection (CHMI) study has now been initiated to determine efficacy of preventing infection and thereby clinical malaria.

ProC6C/Matrix-M is a first-in-class multi-stage malaria vaccine aimed at eliciting both transmission reducing activity and direct personal protection, with the goal of extending both community and individual benefits. The antigen is a novel single recombinant protein targeting three malaria antigens: Pfs230, Pfs48/45 and the Circumsporozoite Protein (CSP).

The results of the first Phase 1 study conducted in Burkina Faso and recently published in the Journal of Clinical Investigation, was the first human trial evaluating a malaria vaccine comprised of the Pfs48/45 antigen. In the Burkina Faso study, ProC6C/Matrix-M became the first malaria vaccine to demonstrate functional transmission-reducing activity in humans from the Pfs48/45 antigen - where 13/20 (65%) volunteers immunized with 100 μg ProC6C-AlOH with Matrix-M, showed greater than 80% transmission reducing activity (TRA). Interim analysis of the second Phase 1 clinical trial conducted in Mali demonstrated similar findings. ProC6C/Matrix-M has also demonstrated the ability to induced high antibodies against the Circumsporozoite Protein (CSP), the leading malaria vaccine target to prevent parasite infection, in those same human volunteers. The ability of these CSP antibodies to prevent infection will now be assessed in this Phase 2 study.

“We’ve long known from preclinical data that Pfs48/45 would be a good transmission-blocking vaccine candidate,” said Professor Michael Theisen, SSI, who has led malaria vaccine development at SSI for decades: “Having confirmed that transmission objective in the Phase 1 studies, we are now excited to evaluate the ability of our short CSP sequence in that same immunogen to prevent infection.”

“The past years have taught us that having multiple interventions are critical to controlling disease, and the advancement of ProC6C/Matrix-M into efficacy trials is an exciting opportunity to offer another possible control measure through novel vaccine designs and collaborative approaches,” said Jordan Plieskatt, CSO, Praestans BioSciences, and Product Development lead for the project. “The PfTBV consortium founded in 2019 through funding by the European Union And Developing Countries Clinical Trials Partnership (EDCTP2) demonstrates the capabilities of the European-African partnerships to accelerate new candidates and strengthen capacities together.”

The Phase 1 data supported the robust enhancement of immune responses by the inclusion of the Matrix-M Adjuvant with ProC6C – and the ProC6C/Matrix-M combination was selected for further evaluation in this Phase 2 trial.

Phase 2 clinical trial

The randomized, double-blind Phase 2 clinical trial, termed “TBVax3” will be led by Dr. Issaka Sagara and conducted at the Malaria Research and Training Center (MRTC) together with the University of Sciences, Techniques and Technologies of Bamako (USTTB) in Sotuba, Mali, through the PfTBV consortium established in 2019.

“The PfTBV consortium was established to rapidly evaluate malaria vaccines from our US and European Partners, and our well-established centers in Mali have allowed just that,” said Dr. Issaka Sagara, coordinator of the EDCTP project and Principal Investigator of the Phase 2 study of ProC6C/Matrix-M: “We are well pleased to see new vaccines advance and the valuable contributions that our communities make to this endeavor.”

Healthy adults (18-50 years old) will receive three immunizations of ProC6C together with the Matrix-M adjuvant. Following the last vaccine dose, individuals will be “challenged” by direct infection with the P. falciparum malaria parasite and followed daily to determine the time to patent parasitemia (presence of parasite in the blood). The primary objectives of the study are to assess safety, tolerability, and the protective efficacy of ProC6C/Matrix-M against P. falciparum infection. Controlled Human Malaria Infection (CHMI) models are an established methodology for evaluating the efficacy of pre-erythrocytic and asexual blood-stage malaria vaccine candidates and drugs, both in malaria-naïve volunteers and in prior-exposed adults in malaria-endemic regions. Initial results are expected in late 2024 and the data will inform the advancement of ProC6C/Matrix-M as a standalone malaria vaccine.



This project is part of the EDCTP2 Programme supported by the European Union
And Developing Countries Clinical Trials Partnership (Grant number RIA2018SV-2311). The views and opinions of authors expressed herein do not necessarily state or reflect those of EDCTP.

About Malaria

Malaria is one of the most common tropical infectious diseases. Despite the available medication, insecticides, and mosquito nets, more than 200 million people annually contract the disease, resulting in nearly half a million deaths. Malaria is caused by a parasite called Plasmodium, which is transmitted from one human to another via mosquitoes. When a mosquito bites a malaria patient, parasites can be transferred to the mosquito. The parasites continue to develop in the mosquito, ultimately making the mosquito's saliva contagious to other people the next time it bites. ProC6C targets to disrupt this transmission while also inducing antibodies to the CSP, prevent liver invasion of the parasite and disease progression in the individual.

About ProC6C

ProC6C is a new vaccine that can block the spread of malaria while inducing immune responses against the Circumsporozoite protein (CSP) to elicit personal protection from infection in a population. It is comprised of three antigen fragments fused as a single soluble protein (“Pro” originating from a sequence derived from Pfs230 pro-domain, “C” originating from a sequence derived from CSP, and “6C” includes the 6 Cysteine domain of Pfs48/45). In the prior Phase 1 studies conducted (Referred to as TBVax1 (Burkina Faso) and TBVax2 (Mali), the active substance ProC6C was combined with two adjuvants Alhydrogel and Matrix-M™ to enhance the immune response. The vaccination does not cure malaria.

About Matrix-MTM Adjuvant

 When added to vaccines, Novavax's patented saponin-based Matrix-M adjuvant enhances the immune system’s response, making it broader and more durable. The Matrix-M adjuvant stimulates the entry of antigen-presenting cells at the injection site and enhances antigen presentation in the local lymph nodes. Novavax, a global company based in Gaithersburg, Md., U.S., with a differentiated vaccine platform that combines a recombinant protein approach, innovative nanoparticle technology and Novavax's patented Matrix-M adjuvant to enhance the immune response. Matrix-M adjuvant is included in the University of Oxford and Serum Institute of India's R21/Matrix-M malaria vaccine.

 About the PfTBV Consortium

 The PfTBV Malaria Blocking Transmission Consortium was formed in 2019 to develop and execute on a strategy to compare, select and develop malaria vaccine candidates. Using innovative trial designs, the consortium will 1) accelerate well-established candidates into the clinic for direct comparison and evaluation 2) select the most efficacious malaria vaccine to stop transmission of Plasmodium falciparum (Pf) from humans to mosquitoes, and 3) establish assays, endpoints, and regulatory pathways for definitive efficacy assessment of a transmission blocking vaccine (TBV). The consortium is led by the project coordinator Professor Dr. Issaka Sagara. For more information:

 About Statens Serum Institut (SSI)

 SSI is a public enterprise operating as a market-oriented production and service enterprise. Statens Serum Institut is an enterprise under the Danish Ministry of the Interior and Health, and the Institut’s duties are partly integrated in the national Danish health services. The Statens Serum Institut aims to ensure advanced control of infectious diseases, including new infections and biological threats. The institute also strives to be a highly regarded and recognized national and international research, production, and service enterprise.
Press contacts
Contact Statens Serum Institut’s press department at telephone number +45 2260 1123 or e-mail

Press contacts

Contact Statens Serum Institut’s press department at telephone number +45 2260 1123 or e-mail