SARS-CoV-2 Variant Immunology and Vaccine Efficacy

SARS-CoV-2 has evolved through successive variants with mutations in the spike protein that alter transmissibility and antigenicity. The immune response elicited by infection or vaccination targets the spike receptor-binding domain (RBD), leading to production of neutralising antibodies and establishment of immunological memory. However, antigenic drift in emerging lineages such as Omicron and its subvariants has undermined the efficacy of first-generation vaccines and monoclonal-antibody therapies. Immune imprinting, whereby the initial exposure to the ancestral spike shapes subsequent responses, can restrict the breadth of neutralisation against divergent strains. Recent research highlights strategies to broaden immunity, including variant-specific boosters, bivalent vaccines and repeated exposures that refine the antibody repertoire through germinal-centre reactions. Understanding the interplay between viral evolution and host immunity is critical to inform vaccine composition, booster schedules and public-health policies on a global scale.

Research from Nature Portfolio

Studies in animal models and human cohorts demonstrate that repeated booster doses targeting Omicron variants can overcome immune imprinting from the ancestral strain, generating a more diverse array of high-affinity neutralising antibodies against antigenically distinct sublineages. Investigation of breakthrough infections and vaccination regimens has revealed convergent evolution in the RBD of Omicron subvariants, driven by humoral selective pressure that focuses on escape mutations while preserving ACE2 binding. Work on the latest subvariants such as BA.2.75.2, BA.4.6 and BQ.1.1 confirms marked reductions in serum neutralisation and diminished efficacy of authorised monoclonal antibodies, underscoring the need for updated vaccine formulations and next-generation antibody therapeutics.

SARS-CoV-2 Variant Immunology and Vaccine Efficacy publication trend

The graph below shows the total number of articles in sars-cov-2 variant immunology and vaccine efficacy across all publications each year (not limited to Nature Index journals).

Technical terms

Immune imprinting: The tendency of the immune system to preferentially recall responses to antigens encountered during the first exposure, which can limit recognition of divergent variants.

Germinal centre: A specialised microenvironment within lymph nodes where B cells proliferate, undergo mutation and selection to produce high-affinity antibodies.

Neutralising antibody: An antibody that binds a virus and directly prevents it from infecting host cells.

Receptor-binding domain (RBD): The region of the SARS-CoV-2 spike protein that engages the host ACE2 receptor and is the primary target of neutralising antibodies.

References

1. Repeated Omicron exposures override ancestral SARS-CoV-2 immune imprinting. Nature (2023).
2. Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution. Nature (2022).
3. Resistance of Omicron subvariants BA.2.75.2, BA.4.6, and BQ.1.1 to neutralizing antibodies. Nature Communications (2023).
4. Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants. Cell (2022).
5. Immune imprinting, breadth of variant recognition, and germinal center response in human SARS-CoV-2 infection and vaccination. Cell (2022).
6. XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against XBB subvariants and JN.1. Cell Host & Microbe (2024).