Combination Attenuation Offers Strategy for Live Attenuated Coronavirus Vaccines

Journal Article
Journal of Virology, vol. 92, iss. 17, 2018
Vineet D. Menachery, Lisa E. Gralinski, Hugh D. Mitchell, Kenneth H. Dinnon, Sarah R. Leist, Boyd L. Yount, Eileen T. McAnarney, Rachel L. Graham, Katrina M. Waters, Ralph S. Baric, Tom Gallagher
Emergent coronaviruses remain a significant threat to global public health and rapid response vaccine platforms are needed to stem future outbreaks. However, failure of many previous CoV vaccine formulations has clearly highlighted the need to test efficacy under different conditions and especially in vulnerable populations such as the aged and immunocompromised. This study illustrates that despite success in young models, the 2′O methyltransferase mutant carries too much risk for pathogenesis and reversion in vulnerable models to be used as a stand-alone vaccine strategy. Importantly, the 2′O methyltransferase mutation can be paired with other attenuating approaches to provide robust protection from heterologous challenge and in vulnerable populations. Coupled with increased safety and reduced pathogenesis, the study highlights the potential for 2′O methyltransferase attenuation as a major component of future live attenuated coronavirus vaccines.
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