In late 2021, the World Health Organization (WHO) designated the SARS-CoV-2 omicron variant (B.1.1.529) as a variant of concern. This classification arose due to specific mutations in the virus that were believed to enhance transmissibility and increase the risk of reinfection or breakthrough infections in vaccinated individuals. Notably, many of these mutations impact the receptor-binding domain and N-terminal domain of the spike protein. These changes can paradoxically boost the virus’s ability to bind to ACE-2 receptors while enabling it to evade recognition by antibodies, raising alarms among health experts worldwide.
The emergence of omicron exhibited parallels with the beta variant (B.1.351) that was first identified in South Africa. Research indicated that infection-naive individuals who received two doses of the adenoviral vector vaccine AZD1222 (ChAdOx1 nCoV-19) or the mRNA vaccine BNT162b.2 showed reduced neutralising antibody levels against the beta variant. Nevertheless, real-world data suggested that the effectiveness of these vaccines against severe disease and hospitalisations remained high, exceeding 80%.
As the pandemic unfolded, preliminary evidence emerged indicating that booster doses could enhance protection against omicron. Current studies are underway to assess the overall effectiveness of vaccines against this variant. Given the natural delay between infection and the onset of severe outcomes, public health officials are eager for more comprehensive data regarding omicron’s impact on vaccination effectiveness, which remains the key goal of vaccination campaigns.
In the interim, the South Africa National Institute for Communicable Diseases shared early findings revealing a decoupling of infection rates from hospitalisations and deaths associated with omicron. This decoupling suggests robust underlying immune responses following infection, where both primary and booster vaccinations could mitigate the severity of the illness.
Upon infection or vaccination, the body activates complementary humoral (antibody) and cellular (T cell) immune responses. The T-cell response encompasses a diverse array of spike-protein-specific T-cell receptors capable of recognizing multiple epitopes, both within and outside the mutated regions of variants of concern. This implies that even if spike protein mutations allow the virus to escape neutralising antibodies, other immune responses can still confer protection. Notably, the beta variant had minimal mutations affecting T-cell epitopes, and it is anticipated that the omicron variant will behave similarly.
As omicron spreads, it primarily affects populations where individuals have previously been infected with SARS-CoV-2 and have since received vaccinations. In these groups, a greater depth of antibody response and a broader poly-epitopic T-cell response is expected, potentially overcoming some of the anticipated antibody evasion posed by omicron. Most severe disease cases and hospitalisations related to omicron have predominantly been reported among unvaccinated individuals. Consequently, public health experts advocate for an accelerated and equitable rollout of COVID-19 vaccines, emphasizing their continued importance in bolstering protection against omicron.
In light of these developments, collaboration between health organizations, governments, and vaccine manufacturers remains crucial. Noteworthy contributions have been made by institutions like the Bill & Melinda Gates Foundation, the South African Medical Research Council, and various pharmaceutical companies, which have supported research and clinical trials to combat the pandemic.
As we move forward, understanding the dynamics of the omicron variant and its interactions with the immune response will be essential in guiding vaccination strategies and public health interventions to safeguard populations worldwide.