Decreased Antibody Responses to Ad26.COV2.S Relative to SARS-CoV-2 mRNA Vaccines in Patients With Inflammatory Bowel Disease

Abstract

C urrently, 3 vaccines have been granted Emergency Use Authorization for coronavirus disease 2019 prevention in the United States. These include the messenger RNA (mRNA) platform vaccines (mRNA-1273; Moderna/National Institutes of Health) and BNT162b2 (Pfizer-BioNTech) and an adenovirus vector vaccine (Ad26.CoV2.S; Johnson & Johnson), which were 94%, 95%, and 67% effective against COVID-19 infection in their phase III registry trials against the endemic variants at the time, respectively. 1-3 All 3 vaccines target the viral spike (S) protein that facilitates severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into host cells via its receptor binding domain, which interacts with angiotensin-converting enzyme 2. 4 Although the mRNA platform vaccines are 2-dose vaccines administered 3-4 weeks apart, the Ad26.CoV2.S is administered as a single dose. Another adenovirus vector vaccine (ChAdOx1; Astrazeneca), not yet authorized in the United States, is intended as a 2-dose regimen with an interval of 8-12 weeks.Patients with inflammatory bowel disease (IBD) on corticosteroids, immunomodulators, and advanced therapies may have normal to slightly decreased humoral responses to the SARS-CoV-2 mRNA vaccine platforms. 1 In addition, patients receiving infliximab and/or thiopurines have significantly lower rates of seroconversion than those on vedolizumab monotherapy after a single dose of either BNT162b2 or ChAdOx1. 2 A study of solid organ transplant recipients showed decreased humoral responses to Ad26.CoV2.S vaccine relative to both mRNA platform vaccines, although it is unknown whether these findings are generalizable to other immune compromised populations. 5 Q5 We aimed to assess for differences in serologic responses among patients with IBD who received Ad26.CoV2.S relative to those receiving mRNA-1273 or BNT162b2. Among 353 vaccine recipients with IBD participating in a prospective SARS-CoV-2 vaccine registry without prior COVID-19 infection and who had completed a full vaccine regimen, 148 (42%), 193 (55%), and 12 (3%) received mRNA-1273, BNT162b2, and Ad26.CoV2.S, respectively. Demographic and disease characteristics were similar across vaccine groups (mean age, 51 years, 62% were female) (Supplementary Table 1). Approximately 290 (83.1%) participants were on immune-modifying therapies (IMTs), as defined by receipt of advanced therapies (biologics or JAK inhibitors, 80.2%), immunomodulators (16.6%), and/or systemic corticosteroids (6.6%) at the time of initial vaccination. At least 2 weeks after completion of the vaccine regimen, positive antibody levels were detected in 121 (100%), 142 (99%), and 9 (90%) patients receiving mRNA-1273, BNT162b2, and Ad26.CoV2.S, respectively (Figure 1A). Quantitative log 10 (anti-Spike IgG

The T-cell clonal response to SARS-CoV-2 vaccination in inflammatory bowel disease patients is augmented by anti-TNF therapy and often deficient in antibody-responders

“…Taken together, these observations on age, sex, and immunotherapies have potential significance when considering groups to prioritize for SARS-CoV-2 reimmunization. We also observed suggestive signals for vaccine type on the T-cell clonal response, analogous to the reduced levels of antibody response with Ad26.SARS.CoV.2 in this same cohort 5 . Due to the small number of Ad26.SARS.CoV.2 recipients studied, those differences should be interpreted with caution.…”

“…Consistent with reported kinetics of polyclonal functional T-cell response to vaccination 10 – 12 , T-cell clonal response peaked two weeks after the second vaccination dose. Although antibody response also peaks at 2 weeks 5 , antibody levels provided limited predictiveness for the T-cell clonal response induced by vaccination, particularly for individuals with a low T-cell response. This is consistent with findings reported from polyfunctional T-cell assessment 10 , 11 , 13 , 14 .…”

“…Inflammatory bowel disease patients (N=303) were recruited in Los Angeles, CA, USA between January and June 2021 under the CORALE-IBD protocol approved by the Cedars Sinai Institutional Regulatory Board. Details of this cohort were recently reported 5 , 6 . Participants completed baseline surveys detailing demographics and medical history at the time of vaccination, and were offered blood sampling after dose 1 (from 5 days after dose 1 until the day of dose 2), after dose 2 (from 2 to 13 days after dose 2), and at 2 weeks (14 to 29 days after dose 2), and 8 weeks (30 to 84 days after dose 2).…”

“…Plasma antibodies to the receptor binding domain of the S1 subunit of the viral spike protein [IgG(S-RBD)] were quantified using the SARS-CoV-2 IgG-II assay (Abbott Labs, Abbott Park, IL). as previously described 5 .…”

Therapies for inflammatory bowel disease do not pose additional risks for adverse outcomes of SARS‐CoV‐2 infection: an IG‐IBD study

“…The ongoing SARS‐CoV‐2 vaccination program has also raised an important clinical question about the eligibility of IBD patients for priority access to primary vaccination and booster doses. On one hand, this decision could be supported by evidence of a lower serological response to vaccines or natural infection, related to either IBD itself 15 or IBD therapies, namely anti‐TNF agents. 16 , 17 On the other hand, if priority access is granted to people at higher risk of adverse COVID‐19 outcomes, should this apply to some or all IBD patients?…”