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)Sidler, D., Born, A., Schietzel, S., Horn, M. P., Aeberli, D., Amsler, J., Moeller, B., Njue, L. M., Medri, C., Angelillo-Scherrer, A., Borradori, L., Seyed Jafari, S. M., Radonjic-Hoesli, S., Chan, A., Hoepner, R., Bacher, U., Mani, L.-Y., Iype, J. M., Suter-Riniker, F., Staehelin, C., Nagler, M., Hirzel, C., Maurer, B., Moor, M. B.
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)
In this study they look at anti-Spike response and it is remarkably high at 88% compared to some studies. This is in part due to the assay target used but one also imagines there are other explanations. It as to be said that the people taking anti-CD20 had a variety of conditions including transplantation, cancer and autoimmune diseases, many of which was not MS. Also the interval between vaccine and CD20 dosing was years and B cell numbers were above a few cells. However the important element of this study was that when people who had not converted after two doses 26/32 remained negative after a third booster the 6/32 (19%) that were positive had their vaccine some time (> 1-2 year) after CD20 depletion. So this suggests to me that many of the anti_CD20 antibody treated MSersthat did not make a vaccine response after two doses are unlikely to make an antibody response atfer a booster if they stuck to the standard 6 monthly dosing schedule.
I suspect that this will apply to many of you as you will already of had your boosters without any delay in your dosing schedule.
This probably means that without the antibdy response you defence against infection is reduced, We hope that you T cells can do the job of clearing the virus and remember there now a number of anti-viral options available if you do get infected.
Maybe people will read and assimilate the information out there to help people to make an antibody response. If you are not taking anti-CD20, it appears that antibody levels after boosters will be enhanced (see below)
Antibody titers before and after booster doses of SARS-CoV-2 mRNA vaccines in healthy adults Demonbreun, A. R., Sancillo, A., Vaught, L. A., Reiser, N. L., Pesce, L., McNally, E. M., McDade, T. W. MedRXIv 10.1101/2021.11.19.21266555
Two-dose messenger RNA vaccines (BNT162b2/Pfizer and mRNA-1273/Moderna) against
SARS-CoV-2 were rolled out in the US in December 2020, and provide protection against
hospitalization and death from COVID-19 for at least six months. Breakthrough infections have
increased with waning immunity and the spread of the B.1.617.2 (Delta) variant in summer
2021, prompting approval of boosters (for all adults over 18 in the US and currently over 40 in UK). We measured anti-receptor binding domain (RBD) IgG and surrogate virus neutralization of the interaction between SARS-CoV-2 spike protein and the human angiotensin-converting enzyme (ACE2) receptor, before and after
boosters in N=33 healthy adults. We document large antibody responses 6-10 days after
booster, with antibody levels that exceed levels documented after natural infection with COVID19, after two doses of vaccine, or after both natural infection and vaccination. Surrogate neutralization of B.1.617.2 is high but reduced in comparison with wild-type SARS-CoV-2. These data support the use of boosters to prevent breakthrough infections and suggest that antibody-mediated immunity may last longer than after the second vaccine dose.
How much antibody do you need to give protection. It seems it can be assessed
Protective characteristics of COVID-19 convalescent and post-vaccination IgG antibodiesKlegerman, M. E., Peng, T., Seferovich, I., Rahbar, M. H., Hessabi, M., Tahanan, A., Wanger, A., Grimes, C. Z., Ostrosky-Zeichner, L. Z., Koster, K., Cirillo, J. D., Abeydeera, D., De Lira, S., McPherson, D. D.10.1101/2021.11.19.21266547
“a protective Ab level of 7.5 µg/ml was determined, based on 95% of the normal distribution of the post-vaccination population”