Immunology: Resistance to detectable SARS-CoV-2 infection highlights new vaccine targets

Past exposure to other coronaviruses may speed up the clearance of SARS-CoV-2 because the immune system remembers viral replication proteins that are highly conserved across coronaviruses, a paper in Nature indicates. Healthcare workers at high risk of SARS-CoV-2 exposure were studied, and, despite testing negative for SARS-CoV-2 infection or antibodies, they showed signs of elevated memory T cell response against the conserved complex, suggesting that they were able to rapidly clear SARS-CoV-2. The findings highlight the highly conserved proteins as targets for future vaccines against endemic and emerging coronaviruses.

Some individuals at high risk of exposure to the highly infectious SARS-CoV-2 display negative results with standard diagnostic tests. Previous research has suggested that exposure to coronaviruses produces memory T cells that may be effective in attenuating SARS-CoV-2 infection. Mala Maini, Leo Swadling and colleagues hypothesize that pre-existing memory T cells that recognize the proteins of the replication–transcription complex (RTC), a conserved structure involved in viral replication, might facilitate the rapid control of SARS-CoV-2. Designing vaccines that could mimic this expansion of cross-reactive T cells may offer protection against a range of endemic or emerging coronaviruses, the authors conclude.

The authors studied 58 healthcare workers from hospitals in London, UK, who did not test positive for SARS-CoV-2 infection despite high risk of exposure during the first wave of the pandemic in the UK. They compared T cell responses in this cohort with those in matched healthcare workers who did develop laboratory-confirmed SARS-CoV-2 infection. Those individuals who seemed to evade infection had stronger T cell responses, particularly directed against the RTC, than those of individuals who tested positive.