Propelled into the spotlight by the COVID-19 pandemic, mRNA has become a biological entity of great interest in drug discovery – yet mRNA vaccines are just the promising beginning, leading to more and more discoveries and applications. mRNA demonstrates high potential to cure numerous other diseases, as we invite you to discover in this post – let’s take a look at a number of other mRNA based applications with active R&D, establishing mRNA beyond a current trend.

Advances in mRNA Vaccines for Infectious Diseases

It is now admitted that mRNA vaccines provide a safe and long-lasting immune response in humans. Since capping of the mRNA is involved in the protein production into the cells, the capping technologies are of great interest for the development of prophylactic and therapeutic vaccines. In this post, I’ll focus on the CleanCap reagents (Trilink BioTechnologies), and notably the CleanCap AU for the self-amplifying mRNA, as well as their benefits, especially for vaccine approaches against pathogens (including the SARS-CoV-2).

Alpha-Gal-Cer (KRN7000) adjuvant effect in innate and adaptive immunities via dendritic and NKT cells. Source: Alphagalcer.net.

Current cancer vaccine strategies strive to efficiently deliver in situ immunogenic Tumour-Associated Antigens (TAAs) into  functional Antigen-Presenting Cells (APCs).  Stimulated APCs cells then initiate anti-tumour reactions through local and complex immune interactions targeting also the tumour microenvironment.

In this context, Xu et al. have recently developed a new effective oral cancer vaccine platform presenting potent immunogenicity and anti-tumour activity with long-lasting protective memory response (1).

The authors have designed optimized Salmonella-based vectors (Salmonella SPI2-encoded T3SS system) co-administrated with a Natural Killer (NKT) cells ligand (2). The delivery of heterogeneous TAAs into APCs has been proven to display enhanced anti-tumour activity through bacterial expressed TAAs-specific immune reponses.

Chemically synthesized NKT cells ligands (alpha-Galactosylceramide known as the αGalCer KRN7000 or alpha-GalCer) and its superior binding affinity analog 7DW8-5 were already known to enhance the immunogenicity and anti-tumour efficacy of bacterial vaccine vectors (3, 4). α-Gal-Cer is known to exhibit potent antitumor activity in various murine experimental cancer models.

Xu et al. clearly show here the potential interest of 7DW8-5 as a vaccine adjuvant in clinical tumour treatment with oral vaccines.

α-Gal-Cer (KRN7000) specific ligand for natural killer T (NKT) cells.

Sources:

1. Xu et al. “Development of an Effective Cancer Vaccine Using Attenuated Salmonella and Type III Secretion System to Deliver Recombinant Tumor-Associated Antigens” (2014) Cancer Res Published Online First September 11, 2014. DOI:10.1158/0008-5472.CAN-14-1169.
2. Nicol A. et al. “Comparison of clinical and immunological effects of intravenous and intradermal administration of a-galactosylceramide (KRN7000)-pulsed dendritic cells” (2011) Clin Cancer Res, 1;17(15):5140-51. DOI: 10.1158/1078-0432.CCR-10-3105.
3. Xiong G. et al. “Novel cancer vaccine based on genes of Salmonella pathogenicity island 2” (2010) Int J Cancer,126:2622-34. DOI: 10.1002/ijc.24957.
4. Li X. et al. “Design of a potent CD1d-binding NKT cell ligand as a vaccine adjuvant” (2010) Proc Natl Acad Sci U S A 2010;107:13010-5. DOI: 10.1073/pnas.1006662107.