Novel “Inverse Vaccines” Could Soon Target Autoimmune Diseases

A novel class of therapies that are labeled vaccines – known as ‘inverse vaccines’—are designed to treat autoimmune disorders and could be made available in just a few years. In January, Swiss biotech company Anokion—which focuses on improving treatments and health outcomes for individuals suffering with autoimmune disorders—announced promising early human trials of inverse “vaccines” targeting celiac disease and multiple sclerosis (MS), two of the most common autoimmune conditions in the United States.”¹

According to a company press release, “KAN-101 is a novel immune tolerance therapy, which encompasses an established gluten antigen delivered to the liver and immune system using the company’s proprietary liver-targeting technology.” Anokion also revealed a new partnership with Pfizer Ignite, an initiative that “gives biotech companies access to Pfizer’s resources, scale, and expertise to help advance potential breakthrough medicines more rapidly.”¹

Inverse Vaccine Technology “Retrains” Immune System to Not Attack Itself

Unlike conventional vaccines that train the immune system to attack a threat, inverse “vaccines” are designed to have an opposite effect: calming the immune system. The new technology is designed to use synthetic nanoparticles bound to specific antigens to disarm and “retrain” the immune system to stop attacking the body’s own tissues. These synthetic nanoparticles mimic dying cells, so it is thought that the immune system will not register them as dangerous. Instead, the immune system is supposed to learn to tolerate the attached antigens and switch off the self-destructive response that drives autoimmunity.²

Autoimmunity, which affects up to 50 million Americans, is characterized by the body’s defenses mistakenly targeting its own cells. There are more than 80 types of autoimmune disorders. The most common ones include rheumatoid arthritis, type 1 diabetes, multiple sclerosis, and systemic lupus erythematosus (lupus). Other autoimmune disorders include inflammatory bowel disease (IBD), psoriasis, Hashimoto’s thyroiditis, and Graves’ disease. According to Johns Hopkins, the risk for autoimmunity is linked to three factors: genetic susceptibility, immune system imbalances, and environmental triggers.^{2 3}

Northwestern University immunologist Stephen Miller authored a 2021 paper demonstrating the potential effectiveness of inverse “vaccines” to treat autoimmune disorders in humans. The study, which focused on celiac disease—an autoimmune condition where the immune system attacks the intestinal lining when gluten is consumed—gave one group of participants an inverse “vaccine” and the other an intravenous saline placebo. After two weeks, according to the study, the intestinal lining of the inverse “vaccine” group showed no damage while the placebo group experienced worsening symptoms. As the study notes, “The TAK-101 group showed no significant change in VH:CrD ratio [a standard measure of small intestinal health] from baseline to post–gluten challenge, whereas the placebo group demonstrated a significant reduction [meaning tissue injury consistent with active celiac disease].” ⁴

Today’s standard treatments to treat autoimmune disorders typically require daily drugs that suppress the entire immune system, often leaving patients vulnerable to infections and other complications—a trade-off experts believe inverse vaccines could eventually eliminate. Miller told The Guardian, “We want to use a scalpel rather than a sledgehammer to treat these diseases.” He also described the therapy as a “holy grail,” though the study’s authors emphasized that more research is needed to confirm long-term safety and effectiveness.²

Questions and Limitations of Miller’s 2021 TAK-101 Trials

Notably, there are significant limitations and unanswered questions about the Miller study, which tested TAK-101—an experimental therapy that uses tiny biodegradable particles loaded with gluten proteins to retrain the immune system to stop attacking the gut, particularly in people with celiac disease. The study had a short follow-up period, so it is still unclear how long this tolerance might last, whether repeated treatments would be necessary to maintain protection, or whether any adverse effects could surface after the trial period.⁴

The relatively small sample size also limited the power to detect differences in gut tissue protection and symptom outcomes, and participants were only observed over a few weeks. As summarized in their What You Need to Know section, the investigators emphasized that these early studies were “of limited duration” and that “longer-term effects of TAK-101 on celiac disease symptoms were not fully evaluated.”⁴

Miller Study Cites Theoretical Risk of Unintended Immune Effects of Inverse Vaccines

Although no serious adverse events occurred within the study parameters, the safety of repeated or long-term intravenous nanoparticle administration remains unknown, and there is a theoretical risk of unintended immune effects even though the therapy is designed to be antigen-specific. According to the study, “Although no effect of TAK-101 was observed on ex vivo T-cell proliferation and no clinically meaningful changes in vital signs, routine clinical laboratory test results, or serum cytokine/chemokine levels occurred… the durability and broader safety… remain to be determined.”⁴

Additionally, the therapy’s impact on diverse patient populations—especially those with different HLA types (human leukocyte antigens, which are essentially “name tags” on the body’s cells that help the immune system distinguish between self and foreign invaders) or with coexisting autoimmune conditions—is not yet fully characterized. The study also could not confirm whether TAK-101–induced immune tolerance would translate to meaningful symptom improvement in daily life or how it might affect other immune responses, such as those to infections or vaccines. “We were unable to assess whether the protective effects of TAK-101 translated into a reduction in symptoms, as this study design… did not allow adequate granularity to assess symptom differences between groups.”⁴

Anokion Inverse Vaccine Garners Fast-Track Designation From FDA

A couple of years later, in 2023, NYU bioengineer Jeffrey Hubbell—co-founder of the biotech firm Anokion currently working to develop inverse vaccines—published a peer-reviewed study demonstrating that the therapy halted disease progression in a mouse model of multiple sclerosis, an autoimmune disorder affecting the central nervous system.⁵

However, this study faces many of the same uncertainties as Miller’s 2021 trial of TAK-101, including questions about long-term safety, durability of tolerance, effectiveness across diverse patient populations, and the risk of unintended immune effects. Still, in May 2023, Anokion’s related therapy KAN-101 was granted Fast Track Designation by the U.S. Food and Drug Administration (FDA), underscoring the urgency of continued research.¹

Prevalence of Autoimmune Biomarkers in Teens Increased 300 Percent Since Late 1980s

Autoimmune conditions have risen sharply over the last several decades, with some experts, such as Molly Murray, President and CEO of the Autoimmune Association, calling it a major health crisis. As Murray noted in a recent blog post, “Among test subjects, the prevalence of antinuclear antibodies (ANA), the most common biomarker of autoimmunity, nearly doubled between 1988 and 2012. In the same study, the prevalence of ANA among adolescents aged 12 to 19 years old increased nearly 300%.” Over the same period, the U.S. Centers for Disease Control and Prevention (CDC) expanded its recommended childhood vaccination schedule, adding dozens of doses of approximately eight to 10 new vaccines or boosters.^{6 7}

Study Links Vaccines and Adjuvants to Autoimmune Responses in Some Individuals

A 2015 peer-reviewed study published in Pharmacological Research summarized evidence,  including both animal experiments and human case reports, that vaccines and vaccine adjuvants can induce inflammatory responses and autoimmunity in genetically or environmentally predisposed individuals. Aluminum-based adjuvants in particular are highlighted as a concern because they can persist in the body for years, potentially contributing to chronic immune activation or crossing the blood–brain barrier, which could result in neuroinflammation, recognized as a significant factor in Autism Spectrum Disorder (ASD).⁸

Particular attention is drawn to aluminum-based adjuvants due to concerns regarding their prolonged persistence in the body, which may lead to chronic immune activation or penetration of the blood–brain barrier. Such occurrences could result in neuroinflammation, an increasingly 8 significant factor in ASD.¹

The authors advocate for improved vaccine safety research, including trials with proper placebos, rather than aluminum-containing comparators—a renewed focus noted by the U.S. Department of Health and Human Services (DHHS) in recent months. The authors also call for extended observation periods and studies specifically examining autoimmune outcomes—for example, measuring whether people develop autoimmune antibodies, or tracking the incidence of new autoimmune diagnoses after vaccination instead of just looking at general side effects like fever or injection-site pain.^{8 9}

This study adds to a growing body of research exploring a possible link between vaccines—which, by design, trigger a strong inflammatory immune response—and autoimmunity; however, no definitive causal relationship has been recognized by public health authorities.

While experts are hopeful that inverse vaccines are a promising novel therapy, larger and longer trials are essential to fully establish their safety, effectiveness, and clinical benefit. Inverse “vaccines” could potentially obtain FDA licensure within the next three to ten years, depending on the outcomes of ongoing trials. “Twenty years ago, I would have told you this wasn’t possible, absolutely not,” Miller said. “Today, I can say that it will happen. No doubt.”²

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