Cold-Adapted Live Attenuated SARS-Cov-2 Vaccine Completely Protects Human ACE2 Transgenic Mice from SARS-Cov-2 Infection

A safe and effective vaccine that can provide herd immunity against severe acute respiratory syndrome coronavirus (SARS-CoV-2) is urgently needed to stop the spread of this virus among humans. Many human viral vaccines are live, attenuated forms of viruses that elicit humoral and cellular immunity. Here, we describe a cold-adapted live-attenuated vaccine (SARS-CoV-2/human/Korea/CNUHV03-CA22 °C/2020) developed by gradually adapting the growth of SARS-CoV-2 from 37 °C to 22 °C in Vero cells. This vaccine can be potentially administered to humans as a nasal spray. Its single dose strongly induced neutralising antibodies (titre > 640), cellular immunity, and mucosal IgA antibodies in intranasally immunised K18-hACE2 mice, which are very susceptible to SARS-CoV-2 and SARS-CoV infections. The one-dose vaccinated mice were completely protected from SARS-CoV-2 infection and did not show body weight loss, death, or the presence of virus in tissues, such as the nasal turbinates, brain, lungs, and kidneys. These results demonstrate that the cold-adapted live attenuated SARS-CoV-2 vaccine we have developed may be a candidate SARS-CoV-2 vaccine for humans.