Longitudinal analysis of antibody trajectories and humoral responses to a third dose of mRNA vaccines against SARS-CoV-2 in patients with a history of anti-CD20 therapy (RituxiVac 2.0)
Authors: Sidler Daniel , Born Alexander , Schietzel Simeon , Horn Michael P. , Aeberli Daniel , Amsler Jennifer , Möller Burkhard , Njue Linet M. , Medri Cesare , Angelillo-Scherrer Anne , Borradori Luca , Seyed Jafari S. Morteza , Radonjic-Hoesli Susanne , Chan Andrew , Hoepner Robert , Bacher Ulrike , Mani Laila-Yasmin , Iype Joseena Mariam , Suter-Riniker Franziska , Staehelin Cornelia , Nagler Michael , Hirzel Cédric , Maurer Britta , Moor Matthias B. 
Published: November 2021

Background

Morbidity and mortality of COVID-19 is increased in patients with B-cell depleting therapies, the majority of which also show compromised vaccination-induced immune responses. Herein, we report on the trajectories of anti-SARS-CoV-2 antibodies in patients from the original RituxiVac study compared to healthy volunteers and investigate the immunogenicity of a third vaccination in previously non-responding patients.

Methods

A follow-up evaluation was performed in volunteers and patients from the RituxiVac Study (NCT04877496), which investigated the humoral and cell-mediated immune response after SARS-CoV-2 mRNA vaccination in patients with a history with anti-CD20 depleting therapies (rituximab or ocrelizumab). The current population included 33 patients and 26 healthy volunteers with initial humoral vaccine response and 32 non-responding patients. Primary outcome was anti-SARS-CoV-2 antibody trajectories in vaccine responders 4.3 months (median; interquartile range [IQR]: 3.6 – 4.8 months) after first evaluation and humoral responses after a third vaccine dose in previous non-responders. Antibody decay rates were compared using analysis of covariance in linear regression.

Results

In patients with detectable anti-spike IgG antibodies after two-dose vaccination, circulating anti-spike IgG persisted in 88% (29/33) of patients 5.6 months after the second vaccination (median; IQR: 5.1-6.7) compared to 92% (24/26) of healthy volunteers 6.8 months after the second dose (IQR: 6.0-7.1) (p=0.7). Antibody decay rates were comparable between patients and controls with −0.54 signal/cut-off (s/c) units per month (IQR −0.72 to −0.45) and −0.60 s/c units per month (IQR: −0.88 to −0.44), p=0.70. Two-dose responders with loss of circulating antibodies at follow-up (n=4/33, 12%) had lower initial antibody concentrations (p<0.01). Biomarkers for immunocompetence, including CD3, CD4 or CD19 cell count at baseline did not predict anti-spike IgG persistence. In two-dose non-responders, a third dose of mRNA vaccine against SARS-CoV-2 elicited humoral response with detectable anti-spike IgG antibodies in 19% (6/32) participants. No clinical parameters nor biomarkers of immunocompetence predicted humoral response after a third vaccine dose.

Conclusion

The present study reveals comparable antibody reduction rates between patients with CD20-depleting treatment history and healthy volunteers, but inefficient humoral responses to a third dose of SARS-CoV-2 mRNA vaccines in the majority of two-dose non-responders. There is a need for individually tailored vaccination strategies in immunocompromised patients that could be stratified by B cell counts and initial level of antibody titers. (Funded by Bern University Hospital, ClinicalTrials.gov number, NCT04877496)