Abstract
In the prevention and treatment of infectious diseases, mRNA vaccines hold great promise because of their low risk of insertional mutagenesis, high potency, accelerated development cycles, and potential for low-cost manufacture. In past years, several mRNA vaccines have entered clinical trials and have shown promise for offering solutions to combat emerging and re-emerging infectious diseases such as rabies, Zika, and influenza. Recently, the successful application of mRNA vaccines against COVID-19 has further validated the platform and opened the floodgates to mRNA vaccine’s potential in infectious disease prevention, especially in the veterinary field. In this review, we describe our current understanding of the mRNA vaccines and the technologies used for mRNA vaccine development. We also provide an overview of mRNA vaccines developed for animal infectious diseases and discuss directions and challenges for the future applications of this promising vaccine platform in the veterinary field.
Highlights
Vaccination has made a tremendous contribution to human and veterinary medicine [1]
The three formulation components include: (1) an ionizable or cationic lipid material such as 1,2-di-O-octadecenyl-3-trimethylammonium propane (DOTMA), N1,N3,N5-tris (3-(didodecylamino)propyl) benzene-1,3,5-tricarboxamide (TT3), and N,N-Dimethyl-2,3-bis[(9Z,12Z)-octadeca-9,12-dienyloxy]propan-1-amine (DLinDMA) that mediate the encapsulation of the negatively charged mRNA molecules via electrostatic interactions; (2) lipid-linked polyethylene glycol (PEG) and cholesterol that could stabilize the nanoparticles during the preparation and increase the half-life of formulations after in vivo administration; and (3) phospholipids that participate in the formation of the lipid bilayer structure (Figure 3)
Strategies to avoid excessive innate immune responses such as modification of mRNA with pseudouridines should be prioritized in the development of succussive mRNA vaccines
Summary
Vaccination has made a tremendous contribution to human and veterinary medicine [1]. Two major viral diseases, smallpox and rinderpest, have been eradicated worldwide with the help of vaccination [2,3]. Addition of the 5 cap can be achieved either via a post-transcriptional enzymatic reaction guided by the vaccinia virus-capping enzyme or a co-transcriptional reaction by incorporation of the synthetic cap or anti-reverse analogues Additional posttranslational modifications such as 2 -O-methylation to introduce a cap 1 structure into an in vitro transcribed mRNA were proved to further improve the translational efficiency and to prevent undesirable immune responses [31,32,33]. The innate immune response is significantly attenuated in vivo with this modified mRNA, compared to non-modified mRNA [39,40,41] Both the Moderna and Pfizer–BioNTech SARS-CoV-2 vaccines were designed to incorporate pseudouridine in the mRNA molecules [8,13]. These innovations have overcome significant manufacturing bottlenecks in scalable mRNA synthesis processes
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