Malaria Vaccine Research

Despite anti-malarial interventions, incidence of malaria even increased in 2021 [1], possibly in part due to disruptions to control efforts caused by the SARS-CoV-2 pandemic.

The renewed focus on malaria elimination has facilitated an increased research towards development of vaccines to block malaria transmission [2]. Interrupting the transmission of malaria parasites by mosquito from infected to susceptible individuals, may significantly reduce the number of secondary infections, resulting in an overall reduction in disease and mortality [3].

Malaria Transmission Blocking Vaccine

Novel malaria vaccines were developed through the malaria program at SSI under broad support and funding from both the US and EU.

Two vaccine immunogens (R0.6C and ProC6C) were manufactured at SSI [4, 5] and released for clinical evaluation in Europe and West Africa, under the European Developing Countries Trials Partnership (EDCTP). The two novel vaccines, tested together with the Matrix-M (Novavax AB) were found to be safe and highly immunogenic in humans.

After the completion of three clinical trials in healthy adults from both naïve (The Netherlands) and in malaria exposed populations (Mali and Burkina Faso), we have concluded that one vaccine, ProC6C/Matrix-M is superior in eliciting high levels of functional antibodies with the capacity to kill the parasite when it multiplies in the mosquito.

This is the first time that the Pfs48/45 immunogen (included in ProC6C and R0.6C) has been tested in humans, and moreover found to be functional in transmission reducing activity.

Multi-komponent multi-stage malaria vaccine

The long-term goal of our research is to develop a multi-component malaria vaccine, which include components from the different parasite stages. A multi-stage vaccine would be a stronger public health tool than single-stage vaccines since such vaccine would provide not only direct personal protection but also considerably reduce parasite transmission and risk of infection.

One of our candidates, ProC6C, is unique, as it also contains immune dominant epitopes from the Circumsporozoite Protein (CSP), broadening the immune response from transmission reducing to personal protection (prevention of liver invasion of the parasite).

ProC6Cinclude includes six NANP- and three NVDP-repeats which elicited high levels of antibodies that prevent infection by inhibiting sporozoite hepatocyte invasion [5].

ProC6C, is a novel first in its class, multi-stage subunit vaccine (manufactured by SSI) aimed at eliciting both transmission reducing activity and direct personal protection extending both community and individual benefits.

Facts about malaria

Malaria is a vector-borne parasitic disease with asexual proliferation in the human host (malaria attack) and a sexual proliferation in the vector mosquito.

The most serious form of malaria is due to the parasite Plasmodium falciparum, which caused approximately 600,000 deaths in 2021. Of these, approximately 95% occurred among children under five years in sub-Saharan Africa.

Malaria control consists of rapid diagnosis and treatment. Impregnated mosquito nets and mosquito repellent are an important component to break transmission from mosquitoes to humans.

Although there has been a decrease in the number of malaria cases over the past decade, it is commonly assumed that malaria cannot be eradicated with current strategies. An effective vaccine against malaria is therefore a highly sought after target.

[1] Organization WH. World malaria report 2022. Geneza, Switzerland 2022.
[2] Duffy PE, Patrick Gorres J. Malaria vaccines since 2000: progress, priorities, products. NPJ Vaccines. 2020;5:48.
[3] Griffin JT, Hollingsworth TD, Okell LC, Churcher TS, White M, Hinsley W, et al. Reducing Plasmodium falciparum Malaria Transmission in Africa: A Model-Based Evaluation of Intervention Strategies. PLOS Medicine. 2010;7:e1000324.
[4] Singh SK, Plieskatt J, Chourasia BK, Fabra-Garcia A, Garcia-Senosiain A, Singh V, et al. A Reproducible and Scalable Process for Manufacturing a Pfs48/45 Based Plasmodium falciparum Transmission-Blocking Vaccine. Front Immunol. 2020;11:606266.
[5] Singh SK, Plieskatt J, Chourasia BK, Singh V, Bengtsson KL, Reimer JM, et al. Preclinical development of a Pfs230-Pfs48/45 chimeric malaria transmission-blocking vaccine. NPJ Vaccines. 2021;6:120.