The induction of SARS-CoV-2-specific CD8+ T cell immunity uncouples with the viral spread in K18-hACE2 infected mice

Abstract Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 enters the host by infecting nasal ciliated cells. The virus then spreads toward the oropharyngeal cavity, and, in most severe cases, the pulmonary tissues. The antiviral adaptive response is promptly induced in response to virus detection, with virus-specific T lymphocytes appearing before antiviral antibodies. Both breadth and potency of the antiviral CD8 + T cell immunity have a key role in containing viral spread and disease severity. However, how much the spread of infecting SARS-CoV-2 into the respiratory tracts influences the potency of the antiviral CD8 + T-cell immunity is still largely unknown. To fill the gap, we checked the CD8 + T cell immunity induced after infection of K18-hACE2 transgenic mice in conditions where the virus spread is impeded. In detail, mice were infected with SARS-CoV-2 both 3 weeks and 3 months after anti-Spike vaccinations, and virus-specific CD8 + T cell immunity was monitored both before and after infection. We noticed a strong increase of the Spike-specific CD8 + T cell immunity in vaccinated mice six days after infection despite a nearly-full inhibition of the viral replication. Most important, both kinetics and efficiency of the induction of SARS-CoV-2 N-and M-specific CD8 + T cell immunity in vaccinated mice appeared not inferior to those induced in control mice. These results support the idea that the SARS-CoV-2 replication in the lungs does not relevantly influence the generation of virus-specific CD8 + T cell immunity.