Poster Presentation Asia-Pacific Vaccine and Immunotherapy Congress 2024

Developing multi-antigen and multi-species mRNA vaccines against malaria (#139)

Adam Thomas 1 2 , Timothy Ho 1 2 , Lee Yeoh 1 3 , Colin Pouton 4 , Stewart Fabb 4 , Che Ling 4 , James Beeson 1 3
  1. Burnet Institute, Melbourne, VICTORIA, Australia
  2. Monash University, Melbourne, Victoria, Australia
  3. University of Melbourne, Melbourne, Victoria, Australia
  4. Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia

Malaria is still a leading health problem with high numbers of clinical cases and deaths recorded annually, the majority of which are children aged under 5 years. There is an urgent need for effective vaccines to reduce the disease burden and morbidity and enable malaria elimination. Malaria is largely caused by two species, Plasmodium falciparum and Plasmodium vivax. In recent years, recombinant protein vaccine platforms in conjunction with multiple adjuvants have been extensively used in vaccine development for different parasite targets. This includes the RTS,S vaccine, which targets sporozoites that initiate liver infection. However, it has modest and short-lived efficacy requiring regular booster doses and only acts against P. falciparum. Targeting antigens of additional parasite stages in vaccines could achieve greater protection against clinical illness and mortality, and reduce transmission. It is likely that multiple antigens in single vaccine formulations will be needed to improve efficacy. Working towards this gaol, we are evaluating blood-stage Merozoite Surface Proteins (MSP) in the mRNA vaccine platform. This group of proteins have shown promise in early clinical trials and vaccines can induce antibody-dependant complement-mediated and cellular inhibition activity against the parasite. We designed MSP mRNA constructs and successfully expressed them in human HEK293 cells, following which we packaged the mRNA in Lipid Nanoparticles (LNPs) delivery vehicles for mice immunisation and vaccine efficacy studies. Our constructs have shown induction of IgG in mice, confirming the immunogenicity of the expressed antigen in vivo. Functional and inhibitory studies will be performed to confirm the potential protective activity and we will evaluate vaccines designs that achieve long-lasting immunity. The mRNA approach could surpass the current recombinant Virus-Like Particle vaccines and achieve multi-antigen multi-species vaccines to accelerate malaria elimination.