New Insights into Coronavirus Immunity Following COVID-19 Infection and Vaccination
If, like many, you have experienced COVID-19 multiple times or received vaccinations against SARS-CoV-2 (three doses in my case), there is promising news: you may have developed immunity to other coronaviruses that pose a risk to human health or could potentially trigger another pandemic. This conclusion emerged from a study conducted by researchers at King’s College London (KCL) and The Pirbright Institute in the UK.
According to Nazia Thakur, the lead author of the research, the findings suggest that bat coronaviruses, which are currently considered most likely to transmit to humans, are also the ones most likely to be recognised by existing immunity from COVID-19. Thakur noted that while the risk of transmission can never be entirely eliminated, widespread exposure to SARS-CoV-2 may have raised the barrier for related viruses to establish themselves within human populations.
This information should not come as a surprise. Since the pandemic began, experts in infectious diseases and virology have suggested that immunity developed from COVID-19 may also confer protection against other viruses within the coronavirus family. However, to substantiate this hypothesis, further research was necessary, which had to undergo rigorous peer review before publication in academic journals. The study in question was published this month in PLOS Biology.
The Role of Bats in Viral Diversity
Bats are known to host a vast array of coronaviruses, many of which are still relatively unknown. Among these viruses are the sarbecoviruses, a subgenus that includes both SARS-CoV-1 and SARS-CoV-2. Given the association of these viruses with bat coronaviruses and the vast viral diversity they carry, understanding the characteristics that facilitate the jump to other species is crucial for enhancing any epidemiological surveillance efforts.
The recent study aimed to assess the extent to which a coronavirus could utilise various versions of the ACE2 protein—the receptor that many sarbecoviruses exploit to enter cells. Researchers examined 15 representative viruses and tested their spike proteins against ACE2 from 16 bat species and 18 other mammalian species.
This comparative analysis revealed two distinct behaviours: generalist viruses can utilise ACE2 proteins from a wide range of species, while specialist viruses rely on a more limited set of receptors. Notably, generalist behaviour was particularly prevalent among the sarbecoviruses within the same evolutionary group as SARS-CoV-2.
Furthermore, the experiments indicated that the patterns observed with bat ACE2 remained largely consistent when extending the tests to other mammals, including domesticated animals, livestock, rodents, and species considered potential intermediate hosts. This suggests that a broad capacity to utilise ACE2 may be linked to increased flexibility in interacting with different species, although the study does not claim that this characteristic alone dictates the occurrence of zoonotic jumps (transmission from animals to humans).
Immune Recognition and Cross-Neutralisation Potential
The study also investigated another aspect likely to pique interest: how recognisable these viruses are to the immune systems of individuals previously exposed to SARS-CoV-2. To explore this, researchers analysed samples from individuals who had contracted COVID-19 and assessed their ability to neutralise various sarbecoviruses. The results were particularly encouraging for generalist viruses, which demonstrated significant cross-neutralisation and, consequently, greater antigenic similarity to SARS-CoV-2.
Katie Doores, a professor of Viral Immunology at KCL, remarked that these viruses exhibited the greatest antigenic similarity to SARS-CoV-2, meaning they were recognised and neutralised more readily by antibodies developed during COVID-19 infection. Nonetheless, the level of protection was not uniform. While some more distantly related sarbecoviruses retained a degree of recognition by antibodies generated against SARS-CoV-2, they exhibited lower levels of binding and neutralisation. According to Doores, these tended to be ‘specialists’, capable of using ACE2 receptors from a limited number of hosts.
The researchers also identified monoclonal antibodies derived from vaccinated individuals who experienced breakthrough infections, which were capable of recognising a broad range of sarbecoviruses. Ultimately, the study emphasises that SARS-CoV-2 has not remained static. Throughout its evolution in humans, various variants have altered its ability to utilise ACE2 from different animals. In particular, changes in the tropism of Omicron variants and their sublineages were observed, introducing an additional dimension to the issue. A virus that predominantly circulates among humans may acquire characteristics that modify its interactions with other species and potentially facilitate reverse transmission to animals.
Implications for Future Vaccine Development
The authors propose that understanding the relationship between host range, viral evolution, and immune recognition could be instrumental in identifying which sarbecoviruses warrant greater attention. Their findings also hint at the possibility of developing vaccines that provide broader protection against multiple sarbecoviruses.
Dalan Bailey, head of the viral glycoproteins group at Pirbright, expressed optimism about the results, noting that one of the encouraging findings was the evidence of cross-neutralisation even among some of the most distantly related bat coronaviruses. This suggests that broad-spectrum vaccines or therapies could potentially be achieved against sarbecoviruses.