Humoral responses to SARS-CoV-2 vaccination in allogeneic hematopoietic cell transplantation patients resemble that of healthy individuals.

INTRODUCTION

Allogeneic hematopoietic cell transplantation (alloHCT) recipients are at increased risk of severe COVID-19. Although vaccination is strongly recommended, immune responses may vary and can be affected by clinical and treatment-related factors.

METHODS

In this longitudinal, single-center study, we analyzed IgG, IgM, and IgA antibody kinetics to severe acute respiratory syndrome-Corona virus-2 (SARS-CoV-2) spike-1, receptor binding domain (RBD), and nucleocapsid proteins in 354 alloHCT patients and 647 healthy controls by ELISA. A total of 1,364 serum samples were collected before and after one, two, and three doses of mRNA, adenovirus vector, and/or protein-based vaccines. Clinical parameters, including age, conditioning regimen, immunosuppressive therapy, graft-versus-host disease (GVHD), donor type, time since transplantation, diagnosis, and laboratory parameters were evaluated for their influence on antibody responses.

RESULTS

Anti-spike-1 IgG responses increased progressively: 27% of patients versus 28% of controls seroconverted after the first vaccination, 65% versus 59% after the second, and 93% versus 98% after the third. After three doses, no significant differences in IgG prevalence or reactivity remained between groups. IgM and IgA responses were infrequent. Multivariate analysis identified diagnosis, shorter interval between transplantation or vaccination and antibody testing, and lower lymphocyte count as negative predictors after the first vaccination. No negative predictors were detected after the third dose. Antibody levels remained stable for at least six months following the third vaccination. Breakthrough infections occurred but were mild.

CONCLUSIONS

AlloHCT recipients achieve humoral immunity comparable to healthy individuals after three vaccine doses, supporting efficacy and safety of repeated SARS-CoV-2 vaccination in this vulnerable population.