The COVID-19 pandemic, caused by SARS-CoV-2, was the third major outbreak of a coronavirus in the past two decades, following SARS-CoV-1 in 2002 and MERS-CoV in 2012. Numerous coronaviruses circulate among bats and other mammals globally, and as environmental stressors intensify, the likelihood of future outbreaks increases.
Although SARS-CoV-2 vaccines have been widely adopted, the emergence of variants like Omicron has significantly reduced their effectiveness, prompting the development of variant-specific vaccines. It remains unclear whether infection with or vaccination against different SARS-CoV-2 variants offers cross-protection against other coronaviruses circulating in nature.
To investigate this, we measured neutralising antibody (nAb) levels using a pseudovirus neutralisation assay in 132 individuals with a history of SARS-CoV-2 vaccination +/- infection. The panel included coronaviruses isolated from animal reservoirs in Asia, Africa and Europe, as well as SARS-CoV-1 and SARS-CoV-2 variants.
In general, nAb levels were lower for coronaviruses more distantly related to SARS-CoV-2. Infection with the BA.5 variant produced stronger nAb responses against SARS-CoV-2 variants compared to individuals without prior infection, but showed minimal improvement against non-SARS-CoV-2 coronaviruses. Notably, nAb responses to the original (ancestral) SARS-CoV-2 viruses correlated with responses to other divergent coronaviruses, whereas this correlation was absent for the SARS-CoV-2 JN.1 variant.
These findings suggest that immunity from the ancestral SARS-CoV-2 may offer some protection against future coronavirus outbreaks, while immunity from Omicron-derived variants may not. As Omicron variants have replaced the ancestral strain in both circulation and vaccines, population-level immunity against emerging coronaviruses may decline, especially among individuals who have never encountered the ancestral virus. This has important implications for future pandemic preparedness strategies.