Trimpert, JakobJakobTrimpertDietert, KristinaKristinaDietertFirsching, Theresa CTheresa CFirschingEbert, NadineNadineEbertTran, Thi Nhu ThaoThi Nhu ThaoTran0000-0003-3906-4629Vladimirova, DariaDariaVladimirovaKaufer, SusanneSusanneKauferLabroussaa, FabienFabienLabroussaaAbdelgawad, AzzaAzzaAbdelgawadConradie, AndeléAndeléConradieHöfler, ThomasThomasHöflerAdler, Julia MJulia MAdlerBertzbach, Luca DLuca DBertzbachJores, JörgJörgJores0000-0003-3790-5746Gruber, Achim DAchim DGruberThiel, Volker EarlVolker EarlThielOsterrieder, NikolausNikolausOsterriederKunec, DusanDusanKunec2024-10-052024-10-052021-08-03https://boris-portal.unibe.ch/handle/20.500.12422/54126Safe and effective vaccines are urgently needed to stop the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We construct a series of live attenuated vaccine candidates by large-scale recoding of the SARS-CoV-2 genome and assess their safety and efficacy in Syrian hamsters. Animals were vaccinated with a single dose of the respective recoded virus and challenged 21 days later. Two of the tested viruses do not cause clinical symptoms but are highly immunogenic and induce strong protective immunity. Attenuated viruses replicate efficiently in the upper but not in the lower airways, causing only mild pulmonary histopathology. After challenge, hamsters develop no signs of disease and rapidly clear challenge virus: at no time could infectious virus be recovered from the lungs of infected animals. The ease with which attenuated virus candidates can be produced and administered favors their further development as vaccines to combat the ongoing pandemic.enCOVID-19 Roborovski dwarf hamster SARS-CoV-2 Syrian hamster codon pair deoptimization coronavirus genome recoding live attenuated vaccine synthetic attenuated virus engineering500 - Science::570 - Life sciences; biology500 - Science::590 - Animals (Zoology)600 - Technology::610 - Medicine & health600 - Technology::630 - Agriculturearticle10.48350/1607163432040010.1016/j.celrep.2021.109493