The Viral and Vaccine Immunology Lab
All things COVID, Flu and HIV immunology
The ViralVaxLab is a clinical and pre-clinical immunology lab at the University of Melbourne, interested in understanding immunity to viral infections and translating that into novel and effective vaccine platforms. We study antibody, B and T cell responses to respiratory viruses (SARS-CoV-2, Influenza) and chronic infections (HIV, TB) in a variety of clinical cohorts and pre-clinical models.
SARS-CoV-2 breakthrough infection induces rapid memory and de novo T cell responses
Although the protective role of neutralizing antibodies against COVID-19 is well established, questions remain about the relative importance of cellular immunity. Using 6 pMHC multimers in a cohort with early and frequent sampling, we define the phenotype and kinetics of recalled and primary T cell responses following Delta or Omicron breakthrough infection in previously vaccinated individuals. Recall of spike-specific CD4+ T cells was rapid, with cellular proliferation and extensive activation evident as early as 1 day post symptom onset. Similarly, spike-specific CD8+ T cells were rapidly activated but showed variable degrees of expansion. The frequency of activated SARS-CoV-2-specific CD8+ T cells at baseline and peak inversely correlated with peak SARS-CoV-2 RNA levels in nasal swabs and accelerated viral clearance. Our study demonstrates that a rapid and extensive recall of memory T cell populations occurs early after breakthrough infection and suggests that CD8+ T cells contribute to the control of viral replication in breakthrough SARS-CoV-2 infections.