Formulation Development And Improved Stability Of A Combination Measles And Rubella Live-Viral Vaccine Dried For Use In The Nanopatch(Tm) Microneedle Delivery System

Measles (Me) and rubella (Ru) viral diseases are targeted for elimination by ensuring a high level of vaccination coverage worldwide. Less costly, more convenient MeRu vaccine delivery systems should improve global vaccine coverage, especially in low - and middle - income countries (LMICs). In this work, we examine formulating a live, attenuated Me and Ru combination viral vaccine with Nanopatch (TM), a solid polymer micro-projection array for intradermal delivery. First, high throughput, qPCR-based viral infectivity and genome assays were established to enable formulation development to stabilize Me and Ru in a scaled-down, custom-built evaporative drying system to mimic the Nanopatch (TM) vaccine coating process. Second, excipient screening and optimization studies identified virus stabilizers for use during the drying process and upon storage in the dried state. Finally, a series of real-time and accelerated stability studies identified eight candidate formulations that met a target thermal stability criterion for live vaccines (<1 log(10) loss after 1 week storage at 37 degrees C). Compared to -80 degrees C control samples, the top candidate formulations resulted in minimal viral infectivity titer losses after storage at 2-8 degrees C for 6 months (i.e., <0.1 log(10) for Me, and similar to 0.4 log(10) for Ru). After storage at 25 degrees C over 6 months, similar to 0.3-0.5 and similar to 1.0-1.4 log(10) titer losses were observed for Me and Ru, respectively, enabling the rank-ordering of the stability of candidate formulations. These results are discussed in the context of future formulation challenges for developing microneedle-based dosage forms containing stabilized live, attenuated viral vaccines for use in LMICs.