Next-gen supercharged COVID-19 vaccines may also target the common cold
UK researchers investigating a cohort of healthcare workers with a strange pre-existing resistance to SARS-CoV-2 infection have discovered a new antigen target for the next generation of COVID-19 vaccines. The researchers speculate the next wave of vaccines using this antigen could potentially protect against all circulating coronaviruses, including those known to cause the common cold.
Vaccines work by presenting the body with a molecule designed to help the immune system learn how to identify certain pathogens. These molecules are known as antigens, or antibody generators, and the big antigen our first wave of COVID-19 vaccines targeted is the infamous coronavirus spike protein.
Looking to the next generation of COVID-19 vaccines, researchers are looking beyond the spike protein, investigating alternative SARS-CoV-2 antigens. This new research started by studying a cohort of healthcare workers in the UK who strangely seemed to repeatedly test negative to SARS-CoV-2 despite high levels of exposure to the virus.
This cohort consistently tested negative to common antibody and PCR tests, however, the researchers did detect some blood markers suggestive of SARS-CoV-2 infection. An increase in immune T-cells specifically geared to target SARS-CoV-2 was detected, indicating the healthcare workers had potentially experienced a low-level infection but managed to somehow fight it off early.
“We know that some individuals remain uninfected despite having likely exposure to the virus,” explains Leo Swadling, lead author on the new study. “What we didn’t know is whether these individuals really did manage to completely avoid the virus or whether they naturally cleared the virus before it was detectable by routine tests. By intensively monitoring health care workers for signs of infection and immune responses, we identified a minority with this particular SARS-CoV-2 specific T cell response.”
The T-cells detected in the study were trained to target non-structural proteins that play a role in the early stages of the virus’s life cycle. These proteins are part of the virus’s replication transcription complex, more commonly referred to as replication proteins.
Most interestingly, these particular replication proteins are common to all coronaviruses. So the researchers hypothesize those individuals with strong T-cell responses targeting these proteins may have had recent exposure to a more innocuous common-cold-causing coronavirus.
“The regions of the virus that these T cells recognize are highly conserved amongst other members of the coronavirus family, such as those that cause common colds every year,” says Swadling. “Previous common cold exposure may have given these individuals a head start against the virus, tipping the balance in favor of their immune system eliminating the virus before it could start to replicate.”
These findings build on a growing hypothesis suggesting a cross-reactive immune response between SARS-CoV-2 and common coronaviruses. A recent Stanford University study speculated prior exposure to coronaviruses that cause the common cold may explain why some people experience incredibly mild or even asymptomatic forms of COVID-19.
But the most promising implication of this study is the speculation that these replication proteins could be incorporated as antigens into future COVID-19 vaccines. Mali Maini, senior author on the new study, says a vaccine inducing T-cells to target these replication proteins may offer protection against all current coronaviruses, including those that cause the common cold.
Maini also points out a future vaccine would include these newer antigens in addition to those spike protein antigens. This would create a complimentary system with antibodies trained to quickly recognize the spike protein and memory T-cells targeting these replication proteins.
“T cells recognizing the virus’s replication machinery would provide an additional layer of protection to that provided by the spike-focused immunity that is generated by the already highly efficacious current vaccines,” says Maini. “This dual-action vaccine would provide more flexibility against mutations, and because T cells can be incredibly long-lived, could also provide longer-lasting immunity. By expanding pre-existing T cells, such vaccines could help to stop the virus in its tracks at a very early stage.”
The new study was published in the journal Nature.
Source: University College London