Improved Immune Responses to Omicron After Bivalent COVID-19 Booster in CLL Patients

Overview

In a cohort of 84 chronic lymphocytic leukaemia (CLL) patients, bivalent COVID-19 booster vaccines elicited measurable antibody responses in 87% of infection-naïve individuals, with antibody titres comparable to healthy controls. The bivalent booster induced preferential increases in immune responses against the Omicron BA.1 variant, including enhanced neutralising antibody activity and cellular immunity, although neutralisation of newer Omicron subvariants remained limited.

Background

Patients with CLL are significantly immunosuppressed and at high risk of severe COVID-19, with mortality rates up to 33% before vaccines. Despite prioritisation for additional booster doses, prior studies showed suboptimal humoral and cellular responses in this population. The emergence of Omicron variants led to the development of bivalent mRNA vaccines targeting both ancestral and Omicron spike proteins. However, data on the immunogenicity of these bivalent boosters in immunosuppressed patients like those with CLL have been limited.

Data Highlights

Key Findings

• 87% of infection-naïve CLL patients developed measurable antibody responses after bivalent booster, with titres comparable to healthy donors.
• Antibody responses were similar regardless of prior natural SARS-CoV-2 infection or hypogammaglobulinaemia status.
• Bivalent vaccination induced a preferential increase in antibody and neutralising activity against Omicron BA.1 compared to ancestral spike protein.
• Neutralisation of recent Omicron subvariants (BA.4/5, BQ1.1, XBB) remained limited despite vaccination.
• Robust cellular immune responses were observed, with greater increases against Omicron peptides than ancestral peptides.
• A subset of patients, particularly those on Bruton tyrosine kinase inhibitors, remained seronegative after vaccination.

Clinical Implications

Bivalent COVID-19 boosters enhance both humoral and cellular immunity against Omicron variants in CLL patients, supporting their use in this vulnerable population. However, limited neutralisation of emerging Omicron subvariants highlights the need for updated vaccines targeting current circulating strains. Patients who remain seronegative, especially those on immunosuppressive therapies, may benefit from additional protective strategies such as prophylactic antibody administration.

Conclusion

Multiple booster vaccinations with bivalent COVID-19 vaccines improve immune responses against Omicron in CLL patients, though some remain unresponsive and neutralisation of newer variants is suboptimal. Continued vaccine updates and adjunctive protective measures are essential to reduce COVID-19 risk in this immunosuppressed group.

References

1. Cancer Immunology Research 2023 -- Bivalent COVID-19 Booster Immunogenicity in CLL
2. Roche Elecsys Platform Data -- Antibody Measurement Methods
3. General Population Studies on Bivalent Vaccines [1,2,3]
4. Pre-vaccine Era COVID-19 Mortality in CLL [4]
5. Prospective Cohort Study Methods [5]