The latest study conducted by researchers at Washington University School of Medicine in St. Louis found that people who received two doses of the Pfizer COVID-19 vaccine while on TNF inhibitors — a type of immunosuppressant used to treat rheumatoid arthritis and other autoimmune conditions — produced less powerful and shorter-lived antibodies against the virus that causes COVID-19 than healthy people and those on other types of immunosuppressants.

This was notably evident in the virus’s delta strain, according to the researchers.

The good news is that a third vaccine dosage increased antibody levels, but the researchers are unsure how long the levels will remain high. The findings, published online in Med, a Cell Press journal, imply that persons using TNF inhibitors are at an increased risk of developing new infections and would benefit the most from a third dose.

Inflammatory bowel illness, rheumatoid arthritis, and psoriasis are some of the disorders for which TNF inhibitors are used. Endocrinology-related drugs such as etanercept (Enbrel), infliximab (Remicade), cetirizine (Cimzia), and golimumab are in this family (Simponi).

“People taking TNF inhibitors didn’t make as many of the potently inhibitory antibodies, and the ones that they did make had largely decayed by five months after the second dose. So even when compared to other immunosuppressed people, people on TNF inhibitors are probably at greater risk for breakthrough infections, especially as immunity wanes and several months have passed since their initial vaccinations. Our data suggests that they should get boosted,” said the study authors.

A previous study co-led by two of the current paper’s authors — Alfred Kim, MD, PhD, an assistant professor of medicine, and Ali Ellebedy, PhD, an associate professor of pathology & immunology, medicine, and molecular microbiology — demonstrated that 90% of people taking immunosuppressive medications (including TNF inhibitors) produce antibodies following COVID-19 vaccination. However, that study examined the presence or lack of antibodies three weeks following the second shot of the vaccine. The researchers made no attempt to assess the antibody response’s quality.

Diamond and lead author Rita Chen, an MD/PhD student, initiated the new study to assess the quality of antibody response to the Pfizer COVID-19 vaccine in immunocompromised individuals. They were particularly interested in determining whether immunization induces antibodies capable of neutralizing the delta version of SARS-CoV-2, the virus that causes COVID-19. Delta is presently responsible for nearly all occurrences of COVID-19 in the United States.

The study enrolled 77 individuals who were taking immunosuppressive medications to treat diseases such as Crohn’s disease, asthma, or multiple sclerosis. Each participant was on one of thirteen different immunosuppressive drug types, including TNF inhibitors, antimetabolites, antimalarials, and anti-integrin inhibitors. Additionally, 25 healthy individuals were included for comparison.

At three months and then five or six months after the second vaccine dosage, the researchers assessed participants’ antibody responses against the original SARS-CoV-2 strain as well as the alpha, beta, and delta variations.

Three months after their second dose, immunosuppressants had almost the same quantity of total antibodies as healthy people, but their antibodies were of poorer quality. The 12 participants in the research on TNF inhibitors exhibited an abnormally low antibody response. Immunocompromised individuals showed reduced levels of neutralizing antibodies, the most strong type capable of preventing viruses from invading cells without the assistance of the rest of the immune system. Non-neutralizing antibodies can also protect the body by activating a range of immune cells to aid in viral destruction, a capability referred to collectively as effector functions. Additionally, patients receiving TNF inhibitors developed antibodies with diminished effector functions. Immunosuppression had a greater effect on the variations than on the original SARS-CoV-2 strain.

Only 8 percent of healthy patients exhibited levels of neutralizing antibody against delta that were probably too low to be protective three months after the second vaccine dose, whereas 36 percent of all immunosuppressed participants and 67 percent of people taking TNF inhibitors fell below the threshold.

The situation only worsened over time, with TNF inhibitor users faring the worst. Only 17 percent of healthy subjects had gone below the predicted threshold of protection six months following the second treatment. In contrast, five months following the second dose, 58 percent of immunocompromised persons and all TNF inhibitor users had likely lost protection against infection.

The Centers for Disease Control and Prevention (CDC) recommended that individuals with autoimmune diseases have a third dose of the Pfizer and Moderna vaccines while this study was being completed. The researchers were able to find four participants who were using TNF inhibitors and assessed their antibody response one month after receiving the Pfizer vaccine’s third dosage. The shot increased their antibody levels to around 25 times what they were before the third dose, putting them squarely in the protective range.

“What I’ve been telling patients is, ‘If you’re on a TNF inhibitor, definitely get your additional booster dose,” said Kim, who treats patients with autoimmune conditions at Barnes-Jewish Hospital. 

“Getting that additional dose restored responses beautifully. We don’t yet know how long it will last, but for now, it will help protect them.”

The researchers are doing studies to see how long the vaccine’s protection lasts after the third dose.

Source: 10.1016/j.medj.2021.11.004

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