Researchers from the University College London (UCL), in the U.K. have unveiled critical insights into the evolving strategies of the latest SARS-CoV-2 variants, such as BA.4 and BA.5, shedding light on their ability to overcome humans’ innate immunity, marking a crucial turning point in the ongoing battle against the COVID-19 pandemic.
Since the beginning of the pandemic, several variants of the SARS-CoV-2 virus have emerged, with Alpha, Delta, and Omicron successively dominating global circulation. Previous research has highlighted the evolutionary tactics of Alpha and Delta, emphasizing their ability to prevent the human innate immune response by disrupting cellular signaling in the airways. According to researchers, this disruption provides the virus with a window of opportunity to establish itself in the body, eventually overwhelming the adaptive immunity developed through prior infection or vaccination.
Unlike its predecessors, the Omicron variant’s evolution was shaped by the pre-existing immunity within the global population resulting from widespread vaccination and prior infections. The adaptive immunity generated produces antibodies targeting the virus’s spike protein, providing protection against infection through a process known as neutralization.
Published in Nature Microbiology, the study focused on examining eight different sub-variants of the Omicron variant to understand how they interact with the human host. Surprisingly, the earliest Omicron variants, BA.1 and BA.2, exhibited reduced abilities to overcome human innate immunity compared to Alpha and Delta. However, more recent variants like BA.5 and XBB have reacquired this ability, employing similar mechanisms observed in Alpha to Delta variants.
Ann-Kathrin Reuschl, first author of the study from the UCL Division of Infection & Immunity, expressed surprise at the initial findings, stating, “This seemed like a backward step in SARS-CoV-2 evolution and may explain reports of reduced disease severity when these variants were dominant.”
Later Omicron variants, echoing the strategies of Alpha to Delta, increased the production of innate immune antagonist proteins, such as nucleocapsid and Orf6, to overcome innate immunity. The researchers emphasized that this evolution demonstrates how the innate immune system acts as an effective gatekeeper for SARS-CoV-2 variant success.
Despite existing immunity from vaccines and prior infection, the study underscores the virus’s persistent ability to infect individuals. To mitigate infection risk, the researchers suggest the use of FFP3 masks or similar protective measures.
“With SARS-CoV-2 we’ve had a unique opportunity to observe how a virus evolves to overcome our defences in real time, giving us an opportunity to predict what a virus with pandemic potential needs to do to be successful. This may help us to assess the risk posed to humans by emerging viruses or new variants of existing viruses. It will be important to continue to monitor the virus as it continues to evolve,” concluded Clare Jolly, a professor at the UCL Division of Infection and Immunity and senior author of the study.
