A thermostable messenger RNA based vaccine against rabies

Abstract

Although effective rabies virus vaccines have been existing for decades, each year, rabies virus infections still cause around 50.000 fatalities worldwide. Most of these cases occur in developing countries, where these vaccines are not available. The reasons for this are the prohibitive high costs of cell culture or egg grown rabies virus vaccines and the lack of a functional cold chain in many regions in which rabies virus is endemic. Here, we describe the excellent temperature resistance of a non-replicating mRNA based rabies virus vaccine encoding the rabies virus glycoprotein (RABV-G). Prolonged storage of the vaccine from -80°C to up to +70°C for several months did not impact the protective capacity of the mRNA vaccine. Efficacy after storage was demonstrated by the induction of rabies specific virus neutralizing antibodies and protection in mice against lethal rabies infection. Moreover, storing the vaccine at oscillating temperatures between +4° and +56°C for 20 cycles in order to simulate interruptions of the cold chain during vaccine transport, did not affect the vaccine’s immunogenicity and protective characteristics, indicating that maintenance of a cold chain is not essential for this vaccine.

mRNA as a Transformative Technology for Vaccine Development to Control Infectious Diseases

“…In addition, a lyophilized protamine-complexed mRNA vaccine was shown to retain its full biological activity even after exposure to thermal stress conditions for several weeks and up to 36 months at 5 C-25 C. 73,75 Similarly, oscillating temperatures between +4 C and +56 C for 20 cycles, to simulate interruptions of the cold chain during transport, did not impact the protective efficacy of a lyophilized mRNA vaccine in a lethal challenge mouse model. 148 The development of a formulation enabling potent single-dose mRNA vaccines that are thermostable, can be stockpiled, and can simultaneously target multiple antigens and pathogens will have broad utility for a range of diseases, reduce the number and frequency of vaccinations, and alleviate healthcare worker burden. Early clinical evaluation of mRNA vaccines mostly addressed cancer immunotherapy, often with no validated benchmarks to compare.…”

mRNA based SARS-CoV-2 vaccine candidate CVnCoV induces high levels of virus neutralizing antibodies and mediates protection in rodents

“…Following pioneering work using mRNA formulated with protamine to target tumours (Hoerr et al, 2000), (Fotin-Mleczek et al, 2012), (Fotin-Mleczek et al, 2011), (Kubler et al, 2015), CureVac has established that mRNA elicits immune responses against target antigens as a prophylactic vaccine (Stitz et al, 2017), (Lutz et al, 2017), (Schnee et al, 2016), (Petsch et al, 2012), (Alberer et al, 2017). CureVac's proprietary mRNA technology is designed to rapidly identify, produce, and test stable and immunogenic mRNA molecules (Rauch et al, 2018).…”

Enlisting the mRNA Vaccine Platform to Combat Parasitic Infections

“…Previously, RNA was associated with low stability because of the omnipresence of RNases. However, the stability of IVT mRNA at −80 • C can be guaranteed for many months to years when the mRNA is properly capped and purified under sterile conditions [29,83,84]. In fact, a lyophilized mRNA vaccine for rabies has proven to be extremely thermostable [83]; its potency did not drop significantly over several months when the vaccine was stored at oscillating temperatures between 4 and 56 • C. This will be relevant as there is often a lack of a functional cold chain in many of the regions endemic for tropical parasites.…”