Humoral Immune Response in IBD Patients Three and Six Months after Vaccination with the SARS-CoV-2 mRNA Vaccines mRNA-1273 and BNT162b2

Abstract

Severe acute respiratory syndrome coronovirus-2 (SARS-CoV-2) is the cause of the coronavirus disease 2019 (COVID-19) pandemic. Vaccination is considered the core approach to containing the pandemic. There is currently insufficient evidence on the efficacy of these vaccines in immunosuppressed inflammatory bowel disease (IBD) patients. The aim of this study was to investigate the humoral response in immunosuppressed IBD patients after COVID-19 mRNA vaccination. In this prospective study, IgG antibody levels (AB) against the SARS-CoV-2 receptor-binding domain (spike-protein) were quantitatively determined. For assessing the potential neutralizing capacity, a SARS-CoV-2 surrogate neutralization test (sVNT) was employed in IBD patients (n = 95) and healthy controls (n = 38). Sera were examined prior to the first/second vaccination and 3/6 months after second vaccination. Patients showed lower sVNT (%) and IgG-S (AU/mL) AB both before the second vaccination (sVNT p < 0.001; AB p < 0.001) and 3 (sVNT p = 0.002; AB p = 0.001) and 6 months (sVNT p = 0.062; AB p = 0.061) after the second vaccination. Although seroconversion rates (sVNT, IgG-S) did not differ between the two groups 3 months after second vaccination, a significant difference was seen 6 months after second vaccination (sVNT p = 0.045). Before and three months after the second vaccination, patients treated with anti-tumor necrosis factor (TNF) agents showed significantly lower AB than healthy subjects. In conclusion, an early booster shot vaccination should be discussed for IBD patients on anti-TNF therapy.

Serological Responses to the First Three Doses of SARS-CoV-2 Vaccination in Inflammatory Bowel Disease: A Prospective Cohort Study

“…Within-individual analyses also indicated that antibody levels decayed at an approximate rate of 400 AU/mL per week after 2 nd dose and 500 AU/mL per week after 3 rd dose. Decay of antibody titres following vaccine doses has been previously reported; 7,24 however, 3 rd dose antibody titres diminish from a considerably higher baseline as compared to the 2 nd dose vaccine. The threshold level for antibody titres to offer protection from an infection to SARS-CoV-2 is not known.…”

“…26 Our data are consistent with previous studies in demonstrating diminished antibody responses following two doses of a SARS-CoV-2 vaccine for patients on anti-TNF therapy, combination immunosuppressive therapies, and corticosteroids. [6][7][8][9][10][11]24,27,28 In contrast, our study showed that the 3 rd dose of the vaccine yielded high antibody titres across all classes of medications used for maintenance of remission in IBD. However, administration of vaccine while concurrently taking prednisone yielded lower antibody response following 1 st , 2 nd , and 3 rd dose of the vaccine.…”

“…In addition, we did not assess other immune responses to SARS-CoV-2 vaccination, including neutralizing antibodies or T-cell immunity, which may serve as more functional proxies of immune protection over antibody titres. 24,29 Due to logistical constraints in data collection during the pandemic, we were unable to obtain samples corresponding to all vaccine doses for all patients, resulting in semi-independent vaccine dose groups. While a community-based recruitment strategy involving all gastroenterologists in the Calgary zone was utilized, population-based sampling was not possible.…”

Impaired Humoral Immunity with Concomitant Preserved T Cell Reactivity in IBD Patients on Treatment with Infliximab 6 Month after Vaccination with the SARS-CoV-2 mRNA Vaccine BNT162b2: A Pilot Study

“…We therefore conclude that it is still unclear as to what extent long-term humoral response after SARS-CoV-2 vaccination is impacted by immunosuppressive therapies [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ].…”

“…In a previous study, we found an impaired humoral immune response 3 months after second vaccination with an mRNA vaccine, particularly in patients on anti-TNF therapy, compared with healthy control subjects. Six months after the second vaccination, we found, in a cohort of only 4 IBD patients and 7 healthy controls, the first indications of a significantly more divergent humoral immune response in IBD patients compared to healthy controls [ 19 ].…”