Patients with inflammatory bowel disease (IBD) who received the COVID-19 vaccine from Johnson & Johnson produced significantly lower levels of antibodies against the SARS-CoV-2 virus than those who received the Pfizer-BioNTech or Moderna vaccines, according to a study led by Cedars-Sinai.

However, antibodies to the virus that causes COVID-19 represent only one component of immune response, and further research is needed to determine how antibody levels relate to overall protection against the virus, said Gil Melmed, MD, director of Inflammatory Bowel Disease Clinical Research at Cedars-Sinai and lead author of the study, published in the journal Gastroenterology.

IBD refers to a set of chronic diseases, including Crohn's disease and ulcerative colitis, that may cause painful swelling of the intestines, diarrhea and other gastrointestinal symptoms. Because immune system malfunction is one possible cause of IBD, and patients are often treated with immune-modifying medications, there has been concern that vaccines might not produce a sufficient immune response in these patients to protect them against COVID-19.

For their study, Melmed and colleagues examined data on 353 IBD patients who had been fully vaccinated against COVID-19. Most were on immune-modifying therapies.

"Research in organ transplant patients, who are also treated with immune-modifying medications, found that those patients produced very low antibody responses to the Johnson & Johnson vaccine," said Melmed, professor of Medicine. "We did this study to determine whether our IBD patients would have a similar response because that could have implications about which vaccine they should get."

More than 90% of IBD patients in the study produced antibodies in response to COVID-19 vaccines, regardless of vaccine type and whether they were taking immune-modifying medications, a result that Melmed called reassuring. However, IBD patients receiving the Johnson & Johnson vaccine had significantly lower levels than those receiving the two other vaccines.

Melmed suggested that the vaccine mechanism and number of doses could account for this result. The Johnson & Johnson vaccine relies on modified adenovirus—a common virus that causes cold and flu symptoms—to deliver genetic code for the SARS-CoV-2 signature spike protein to cells, causing the immune system to produce antibodies that protect against it. In contrast, the Pfizer-BioNTech and Moderna are mRNA vaccines that deliver SARS-CoV-2 genetic code directly to host cells in the body.

"The mRNA vaccines may have a more potent mechanism for inducing antibody response," Melmed said. "And because they are delivered in two doses, rather than one dose like the Johnson & Johnson vaccine, they provide two immunological hits."

Although only about 3% of IBD patients participating in the registry had received the Johnson & Johnson vaccine, Melmed said the study's findings were consistent with research in other types of immune-compromised patients and were highly statistically significant, sending "a strong signal that vaccine type matters."

But he cautioned against drawing overly broad conclusions from the findings.

"Antibodies, which work to prevent infection from taking hold in the body, do not tell the whole story," Melmed said. "It’s possible that some people develop a strong T cell immunity independent from antibody immunity, and there is published data indicating that the Johnson & Johnson vaccine elicits a strong T cell response."

T cells identify and kill cells infected by the virus, and Melmed said strong T cell response could offer patients very good protection against getting sick. Studies of breakthrough COVID-19 infections in fully vaccinated patients are needed to correlate antibody levels and T cell response with actual protection against infection, and Melmed and colleagues are gathering that data.

"Once we understand the correlation between individuals who get breakthrough infections and their antibody and T cell responses to the vaccines, we will be able to connect the dots and hopefully determine the antibody and T cell thresholds for protection against COVID-19," Melmed said. "We will then be able to predict who needs booster doses or other additional forms of protection."

First author for the Gastroenterology study was Valeriya Pozdnyakova, a clinical research associate in the Braun Lab, and co-authors included Dermot P. McGovern, MD, PhD, the Joshua L. and Lisa Z. Greer Chair in Inflammatory Bowel Disease Genetics and professor of Medicine and Biomedical Sciences; and Jonathan G. Braun, MD, PhD, professor of Medicine at the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute.

"Our studies continue, and we are working to learn more about the duration of antibody response, and how it is affected by medication and the different vaccines," said McGovern. "A more thorough understanding of antibody response and the factors that influence it will help us determine the best way to protect immune-compromised patients against COVID-19."

The research was part of a collaboration with the NCI-funded SeroNet-Coronavirus Risk Associations and Longitudinal Evaluation (CORALE) study, led at Cedars-Sinai by study co-authors Susan Cheng, MD, Erica J. Glazer Chair in Women's Cardiovascular Health and Population Science and professor of Cardiology; and Jane Figueiredo, PhD, director of Community and Population Health Research and professor of Medicine.

Funding: Research reported in this publication was supported by the Cedars-Sinai Precision Health Initiative, the Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, the Leona M. and Harry B. Helmsley Charitable Trust, the Diabetes and Digestive and Kidney Diseases Institute of the National Institutes of Health under award numbers P01DK046763 and U01DK062413, and the Erika J. Glazer Family Foundation.

Disclosures: Gil Melmed, MD, has consulted for Janssen and Pfizer, makers of COVID vaccines, and has received research funding from Pfizer for an unrelated investigator-initiated study. Jonathan G. Braun, MD, has received research funding from Janssen. Dermot P. McGovern, MD, PhD, has consulted for Pfizer.