Last Updated: 06/10/2025
Development of a vaccine candidate against clinical malaria caused by Plasmodium falciparum based on the IGM and IGG response
Objectives
The objective of the project is to conduct preclinical studies of the six chimeric DNA immunogens in the parent DNA vaccine vectors.
- Quality, sterility, safety, and immunogenicity will be assessed in vitro, including cell line assays.
- Safety and immunogenicity will be assessed in mouse models, including T and B cell responses, immunological memory, IgM and IgG humoral immunity, and parasite neutralization by immune sera from vaccinated animals. This will allow immunogens with the best immune responses and protection to be selected to develop a multigenic DNA vaccine.
The ultimate goal is to develop a DNA vaccine candidate that, with two nasal sprays, elicits early IgM responses in children that protect them against severe malaria, thereby reducing mortality when infected.
Malaria, caused by Plasmodium species, affects more than 200 million people annually worldwide. P. falciparum alone accounts for over 600,000 deaths each year, primarily among children under five years of age who develop severe malaria. Two malaria vaccines have recently been approved for use—RTS,S/AS01 (October 2021) and R21 (October 2023). However, their reliance on a single pre-erythrocytic parasite stage target and a complex dosing schedule of three inoculations plus a booster to achieve only partial protection limit their widespread deployment in endemic and remote rural regions.
Through characterization of the circulating P. falciparum IgM antigenome using LC-MS/MS immunocapture followed by peptide microarrays with sera from asymptomatic and symptomatic patients in two malaria-endemic regions (Ghana and the Democratic Republic of Congo), a set of immunodominant IgM epitopes associated with protection in adults was identified. Subsequent analyses of serum IgG responses revealed six antigens in asymptomatic individuals containing high-affinity IgM epitopes that simultaneously react with IgG. Structural and immunogenic redesign of these six antigens, eliminating immune-evasion sequences and enriching for specific protective IgM/IgG epitopes, has produced six soluble chimeric antigens.
This project introduces sequences encoding these chimeric antigens into an antibiotic-free mammalian expression vector to generate DNA vaccine constructs. A DNA vaccine based on this platform has already been authorized by the European Medicines Agency (EMA/CVMP/858971/2022).
The innovative features of this project include:
i) antigens containing epitopes with dual immunological functions (IgM and IgG) correlated with immunodominance in protected asymptomatic carriers;
ii) a simplified vaccination regimen consisting of two single-dose nasal sprays;
iii) efficient, non-invasive administration capable of eliciting a robust immune response without requiring trained healthcare personnel;
iv) safety and ease of administration at room temperature, supported by prior EMA authorization of the vector system; and
v) a novel candidate targeting the erythrocytic cycle, which could complement currently approved pre-erythrocytic malaria vaccines to enhance efficacy, effectiveness, and overall protection.
Once the project is complete, preclinical studies will be conducted in non-human primates.
Jan 2023
$162,298
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