Longitudinal Humoral Response to SARS-CoV-2 Vaccines in Hematopoietic Cell Transplant Recipients

Overview

This prospective study evaluated the antibody responses to one, two, and three doses of SARS-CoV-2 vaccines in 126 hematopoietic cell transplant (HCT) recipients. Results demonstrated significant increases in anti-spike RBD antibody titers and neutralizing activity after vaccination, with the highest responses observed following a third vaccine dose. Factors such as younger age, autologous transplant, longer time from transplant to vaccination, and absence of immunosuppressive therapy were associated with stronger antibody responses.

Background

Patients with hematologic malignancies, especially those who have undergone hematopoietic cell transplantation, are at increased risk for severe COVID-19 outcomes. Vaccination is critical for protection, but the degree and durability of humoral immune responses in HCT recipients remain incompletely understood. Neutralizing antibody activity serves as a surrogate marker for vaccine effectiveness. Longitudinal studies are essential to characterize antibody kinetics and identify factors influencing vaccine response in this vulnerable population.

Data Highlights

Key Findings

• Anti-S RBD antibody titers increased 36-fold one month after the third vaccine dose compared to one month after the second dose.
• Seropositivity rates rose from 40.5% before vaccination to over 98% after the third dose.
• Mean neutralizing antibody activity exceeded the 30% threshold after the second dose and further increased after the third dose.
• Patients aged ≤50 years had significantly higher geometric mean titers (GMTs) than older patients.
• Autologous HCT recipients exhibited higher antibody responses than allogeneic recipients.
• Longer time (>12 months) from transplant to initial vaccination and absence of immunosuppressive therapy were associated with higher antibody titers.

Clinical Implications

These findings support the administration of a third SARS-CoV-2 vaccine dose in HCT recipients to enhance humoral immunity. Clinicians should consider patient age, transplant type, timing post-transplant, and immunosuppressive status when evaluating vaccine response and planning vaccination schedules. Monitoring antibody levels may guide personalized vaccination strategies in this high-risk population.

Conclusion

Hematopoietic cell transplant recipients demonstrate robust increases in humoral immune responses following SARS-CoV-2 vaccination, particularly after a third dose. Tailored vaccination approaches considering individual patient factors can optimize protective immunity against COVID-19 in this vulnerable group.

References

1. Sharma et al. 2021 -- Cancer as a risk factor for poor COVID-19 outcomes
2. Sharma et al. 2021 -- Increased risk of severe COVID-19 in HCT recipients
3. Khoury et al. 2021 -- Neutralizing antibody activity as surrogate for vaccine effectiveness