Optimization of Non-Coding Regions for a Non-Modified mRNA COVID-19 Vaccine

The CVnCoV (CureVac) mRNA vaccine for SARS-CoV-2 has recently been evaluated in a phase 2b/3 efficacy trial in humans1. CV2CoV is a second-generation mRNA vaccine with non-modified nucleosides but optimized non-coding regions and enhanced antigen expression. Here we report a head-to-head study of the immunogenicity and protective efficacy of CVnCoV and CV2CoV in nonhuman primates. We immunized 18 cynomolgus macaques with two doses of 12 ug of lipid nanoparticle formulated CVnCoV, CV2CoV, or sham (N=6/group). CV2CoV induced substantially higher binding and neutralizing antibodies, memory B cell responses, and T cell responses as compared with CVnCoV. CV2CoV also induced more potent neutralizing antibody responses against SARS-CoV-2 variants, including the delta variant. Moreover, CV2CoV proved comparably immunogenic to the BNT162b2 (Pfizer) vaccine in macaques. While CVnCoV provided partial protection against SARS-CoV-2 challenge, CV2CoV afforded more robust protection with markedly lower viral loads in the upper and lower respiratory tract. Binding and neutralizing antibody titers correlated with protective efficacy. These data demonstrate that optimization of non-coding regions can greatly improve the immunogenicity and protective efficacy of a non-modified mRNA SARS-CoV-2 vaccine in nonhuman primates

The importance of the Montreal Protocol in protecting climate

The 1987 Montreal Protocol on Substances that Deplete the Ozone Layer is a landmark agreement that has successfully reduced the global production, consumption, and emissions of ozone-depleting substances (ODSs). ODSs are also greenhouse gases that contribute to the radiative forcing of climate change. Using historical ODSs emissions and scenarios of potential emissions, we show that the ODS contribution to radiative forcing most likely would have been much larger if the ODS link to stratospheric ozone depletion had not been recognized in 1974 and followed by a series of regulations. The climate protection already achieved by the Montreal Protocol alone is far larger than the reduction target of the first commitment period of the Kyoto Protocol. Additional climate benefits that are significant compared with the Kyoto Protocol reduction target could be achieved by actions under the Montreal Protocol, by managing the emissions of substitute fluorocarbon gases and/or implementing alternative gases with lower global warming potentials