Safety and immunogenicity of a mRNA rabies vaccine in healthy adults: an open-label, non-randomised, prospective, first-in-human phase 1 clinical trial

mRNA vaccines — a new era in vaccinology

“…Promisingly, antibody titres were above the expected protective threshold, but they were moderately lower than in the animal models. Similarly to the study by Alberer et al 91 , most vaccinated subjects reported mild to moderate reactogenicity (injection site pain, myalgia, headache, fatigue and chills), and three subjects reported severe injection site reactions or a systemic common cold-like response. This level of reactogenicity appears to be similar to that of more traditional vaccine formats 113,114 .…”

“…As a result, mRNA vaccines have elicited protective immunity against a variety of infectious agents in animal models 19,20,22,56,89,90 and have therefore generated substantial optimism. However, recently published results from two clinical trials of mRNA vaccines for infectious diseases were somewhat modest, leading to more cautious expectations about the translation of preclinical success to the clinic 22,91 (discussed further below).…”

“…In a recently published seminal work, Alberer and colleagues evaluated the safety and immunogenicity of this vaccine in 101 healthy human volunteers 91 . Subjects received 80–640 μg of mRNA vaccine three times by needle-syringe or needle-free devices, either intradermally or intramuscularly.…”

“…Published reports suggest that stable refrigerated or room temperature formulations can be made. The RNActive platform was reported to be active after lyophilization and storage at 5–25 °C for 3 years and at 40 °C for 6 months 91 . Another report demonstrated that freeze-dried naked mRNA is stable for at least 10 months under refrigerated conditions 160 .…”

Delivery of modified mRNA encoding vesicular stomatitis virus matrix protein for colon cancer gene therapy

“…This strategy has been successfully applied for mRNA delivery in several reports including biomedical research and clinical trials. [32][33][34][35] However, the expression efficiency is likely to be inuenced by the length of mRNA, and delivering VSVMP gene in the form of mRNA has not been performed according to our acknowledgement. Furthermore, by mRNA administration, whether the anti-cancer ability or safety of VSVMP gene will be retained is still unknown.…”