The CVnCoV (CureVac) mRNA vaccine for SARS-CoV-2 has recently been evaluated in a half 2b/3 efficacy trial in people1. CV2CoV is a second-period mRNA vaccine with non-modified nucleosides however optimized non-coding areas and enhanced antigen expression. Right here we report a head-to-head research of the immunogenicity and defending efficacy of CVnCoV and CV2CoV in nonhuman primates. We immunized 18 cynomolgus macaques with two doses of 12 ug of lipid nanohalficle formulated CVnCoV, CV2CoV, or sham (N=6/group). CV2CoV induced considerably greater binding and neutralizing antibodies, reminiscence B cell responses, and T cell responses as in contrast with CVnCoV. CV2CoV additionally induced Stronger neutralizing antibody responses in the direction of SARS-CoV-2 variants, collectively with the delta variant. Furtherextra, CV2CoV proved comparably immunogenic to the BNT162b2 (Pfizer) vaccine in macaques. Whereas CVnCoV provided halfial safety in the direction of SARS-CoV-2 problem, CV2CoV afforded extra strong safety with markedly decrease viral masses Inside the greater and decrease respiratory tract. Binding and neutralizing antibody titers correlated with defending efficacy. These knowledge show that optimization of non-coding areas can significantly enhance the immunogenicity and defending efficacy of a non-modified mRNA SARS-CoV-2 vaccine in nonhuman primates.