10.2.1. Prophylactic mRNA Vaccines for Infectious Diseases

Prophylactic vaccine human trials for infectious diseases utilizing mRNA encoding the antigen(s) are shown in Table 3. These are all Phase I trials. Any known formulations are listed, as are any described results and references, along with the clinical trials identifier numbers. The rabies vaccine effort utilizing a licensed vaccine with RNA as the adjuvant (discussed above, and listed in Table 4) was replaced by a vaccine using mRNA encoding the rabies virus glycoprotein. Following either i.d. or i.m. injection of this rabies mRNA vaccine, boostable antibodies were obtained. However, 78% of each group had "solicited systemic adverse events" including ten patients (~10% of all injected patients) with grade three (i.e., serious but not life-threatening) adverse events, although the conclusion was that the vaccine was "generally safe with a reasonable tolerability profile" [55]. A second construct for rabies is now in clinical testing.

As noted earlier, one company initially highlighted a focus on therapeutic disease areas but reprioritized vaccines, possibly due to the recognition of the low amount of antigen actually produced by the mRNA coupled with the low amounts of protein needed for vaccines because of the amplification by the immune system, possibly as a response to emerging diseases such as the Zika epidemic, and possibly influenced by the liver toxicity seen in their pre-clinical studies [59] for delivering even the low amounts of mRNA needed for the disease (Crigler-Najjar, see above). Lipid nanoparticles are also used for that company's vaccine formulations, although it is not known how these relate to the formulation used for Crigler-Najjar (the company has published relatively little in the peer-reviewed scientific literature related to their clinical trials). References, when available, are provided within the table, although in some cases, the assumption is made that the pre-clinical construct in the reference is the same construct (antigen) as the one in the clinical trial.
