mRNA Vaccines Against Parasites
The severe burden of parasitic infections is either not recognized or underestimated, as their co-existence with hosts for decades, forming chronic infections. It is believed that a quarter of the world's population is affected by parasitic infections, such as soil-transmitted helminths and schistosomes. The pathogenesis of parasitic infections is complex and various, traditional vaccine development against parasitic infections is limited due to a lack of thorough understanding. Parasitic infections often occur in tropical countries and mainly impact the poor in regions. Thus, the expense of traditional vaccine platforms might have little link to a traditional return on investment. The mRNA-based technology as a novel and attractive platform is suitable for developing vaccines against parasitic infections. Here, we will give an introduction of the synthesis mRNA as a novel generation of a preventive as well as therapeutic vaccine technology to combat parasitic infections.
Major advantages of the mRNA vaccine against parasitic infections
- Simple and low-cost production and development
The production and purification process of synthesis mRNA can be standardized. Therefore, the cost of production and purification step, as well as the development time for new vaccine candidates, can be dramatically reduced. mRNA vaccine is simple, low-cost, and can be produced in large scale, which is a crucial benefit, especially for people living in low-income countries.
- Safety Profile
Synthesis mRNA is degradable, with no risk for genetic integration as well as the risks associated with whole-cell pathogens.
- The potential to develop multivalent mRNA vaccines
mRNA vaccine can induce immunity to different epitopes from different targets, due to that several antigens can be engineered into an mRNA sequence. The development of multivalent mRNA vaccines can be applied for a pan-parasitic approach, creating a vaccine targeting multiple helminths.
- Strong cellular immune responses
mRNA vaccine has the capability to elicit strong immune responses. It has been demonstrated that mRNA vaccines can induce antigen-specific antibodies as well as strong CD8+ T cell responses. Among them, CD8+ T cell responses play crucial roles in targeting intracellular pathogens.
Enlisting mRNA vaccine platform to fight against parasitic diseases
mRNA vaccines against Toxoplasma Gondii (T. gondii) infection
Based on The Venezuelan equine encephalitis virus (VEEV) replicase proteins, researchers developed a hexaplex self-amplifying mRNA (SAM) vaccine encoding six T. gondii-specific antigens, involving rhoptry protein 2A (ROP2A), dense granule protein 6 (GRA6), rhoptry protein 18 (ROP18), surface antigen 1 (SAG1), apical membrane antigen 1 (AMA1), and surface antigen 2A (SAG2A). Delivered with modified dendrimer nanoparticles (MDNPs), this vaccine provides protection in mice from the lethal challenges of T. gondii Infection. In addition, another study developed a lipid nanoparticle (LNP)-SAM vaccine encoding T. gondii nucleoside triphosphate hydrolase-II (NTPase-II). A partial protective effect of reduced brain parasitic load and prolonged survival time was observed in murine models.
mRNA vaccines against Leishmania Donovani infection
A recent study demonstrated that a subunit vaccine strategy based on a heterologous mRNA can prevent Leishmania donovani infection. Researchers developed a naked mRNA replicon encoding for the LEISH-F2 gene. There was a significant reduction in the parasite burden in the liver when the mice were vaccinated with the F2-mRNA vaccine combined with the recombinant LEISH-F2 protein in glucopyranosyl lipid A in a stable oil-in-water emulsion (SLA-SE). Moreover, the successful heterologous vaccine strategy was characterized by the induction of antigen-specific Th1 responses and very strong IFN-Y secretion by splenocytes.
mRNA vaccines against Malaria infection
Besides, researchers have proved that the protective immunity of the self-amplifying mRNA vaccine encoding Plasmodium macrophage migration inhibitory factor (PMIF) against malaria infection. All studied Plasmodium species express PMIF, which is an orthologue of the mammalian macrophage migration inhibitory factor (MIF). The secretion of PMIF by Plasmodium can attenuate the host's immune response. In order to improve the immunity of the host, researchers vaccinated mice twice with a replicon encoding PMIF. The results showed that the mRNA vaccine delayed blood-stage patency after sporozoite infection. Additionally, both PMIF specific CD4+ cells and the anti-PMIF IgG titer were increased after vaccinations, which enhanced the control of parasites and completely protected from re-infection.
To further promote the development of mRNA vaccines against infectious diseases, Creative Biogene provides a range of customized and inventive solutions, involving the development of influenza mRNA vaccines, anti-parasite mRNA vaccines, mRNA vaccines against HIV as well as the global SARS-CoV-2 pandemic. We are committed to exerting the potential of synthetic mRNA as an important vaccine candidate for infectious diseases, hoping to meet our customers' specific requirements for projects at the preclinical stages. If you are interested in this area, please feel free to contact us. We look forward to providing services for your next project.
- Garcia, A. B.,et al. (2018). "Neutralization of the Plasmodium-encoded MIF ortholog confers protective immunity against malaria infection." Nature communications, 9(1), 1-13.
- Versteeg, L., et al. (2019). "Enlisting the mRNA vaccine platform to combat parasitic infections." Vaccines, 7(4), 122.