In a recent study posted to the medRxiv* preprint server, researchers evaluated cell-mediated immune response (CMIR) in inflammatory bowel disease (IBD) patients following immunization with two doses of coronavirus disease 2019 (COVID-19) vaccine.
The messenger ribonucleic acid (mRNA)-based COVID-19 vaccines, including the mRNA-1273 and BNT162b2 vaccines, effectively protect the general population against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Moreover, several previous studies have demonstrated that 95-99% of IBD patients mounted a measurable antibody response after the two-dose mRNA vaccination series, whereas 100% achieved a substantial antibody response after three doses.
Contrastingly, patients with IBD who were unable to mount an antibody response received the BNT162b2 vaccine. Additionally, they were older, on combination therapy with an anti-tumor necrosis factor-alpha (TNF-alpha) inhibitor and an immunomodulator.
About the study
A prospective, non-randomized study, termed the “HumoRal and CellULar initial and Sustained immunogenicity in patients with IBD” (HERCULES), was conducted at the University of Wisconsin-Madison (UW) and Mayo Clinic Florida (MAYOFL) to evaluate the CMIR of vaccinated IBD patients. The Institutional Review Board at the UW and MAYOFL approved this study.
The researchers created two study cohorts, with 158 participants with IBD and 20 healthy controls (HCs), respectively. The selection criteria for the IBD cohort was that the participants were on stable medication therapy, and HCs had to produce documented proof that they were not on any immunosuppressive therapy and completed their mRNA primary vaccination series.
The primary outcome was the evaluation of CMIR in the cohort of IBD patients against the mRNA-based COVID-19 vaccine. The secondary study outcomes were: i) a comparison of the CMIR in patients with IBD and HCs, and ii) measuring CMIR, as well as a humoral immune response in both the study cohorts.
The researchers measured the humoral immune response and CMIR in IBD patients 28–35 days after the two-dose mRNA vaccine series and at approximately 30 days in HCs, following a similar protocol used for all COVID-19 immunogenicity clinical trials.
The authors could evaluate T cell responses to SARS-CoV-2 spike (S) antigens in 151 patients with IBD and 18 HCs; likewise, they measured anti-S antibody levels in samples of 152 patients with IBD and 18 HCs. Additionally, they observed no significant differences in S-specific T cell responses between those on anti-TNF therapy or Janus kinase inhibitors (JAK) inhibitors compared to other therapies.
While most IBD patients had a CMIR (89%) and a humoral immune response (97%), among HC, only one had a CMIR, and all had a humoral immune response to an mRNA vaccine series.
Also, the authors could not find any compelling evidence of an association between levels of antibody and CMIR, as three of the four participants with no measurable anti-S antibodies showed a CMIR.
Compared to those taking immunosuppressive medication(s), IBD patients not undergoing such treatments had a lower humoral response but not a lowered CMIR.
To summarize, the study findings demonstrated that mRNA vaccine-induced antibody levels and CMIR are not correlated. It indeed is a surprising revelation as in other immunosuppressed populations, for instance, in solid organ transplant recipients, reported CMIR rates are in the range of 36-46%. Similarly, in patients taking B-cell depleting therapy and with psoriasis on an immunomodulator, CMIR rates of 58% and 62-74% have been reported.
The Advisory Committee on Immunization Practices (ACIP) recommended booster dose for those who were moderate to severely immunocompromised based on evidence that solid organ transplant recipients had a suboptimal antibody response (56%) after the primary COVID-19 vaccination series. The humoral immune response in study subjects remained relatively higher than reported in previous studies examining such response in the immunosuppressed populations.
More importantly, the humoral immune response provides an incomplete measure of the COVID-19 vaccine-induced immune response. Additionally, most patients with IBD mounted a vaccine-induced immune response after an mRNA COVID-19 primary series, similar to HCs, suggesting that they might not necessarily require a third dose as previously speculated.
Future studies should specifically evaluate sustained CMIR, the impact of booster dosing on CMIR, and long-term antibody concentrations and CMIR in patients with IBD. In the future, data from such studies could help ascertain whether IBD patients on immune-modifying therapies may benefit from a booster dose or a mix and match immunization strategy and how these therapies may impact sustained humoral and CMIR.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.