Vaccine immunotherapy targeting interleukin 6 (IL-6) has shown promising results in the treatment of inflammatory osteoarthritis of the knee, according to a phase 1 double-blind controlled study. Published in Nature Communications, the results demonstrated a good safety profile and an anti-IL-6 immune response in all treated patients.
Although the trial was not designed to evaluate the clinical efficacy of PPV-06, functional improvement was observed at 42 weeks in patients who received all three doses of the vaccine compared with those in the placebo group. Patients with the highest IL-6 neutralization capacity exhibited the best clinical outcomes.
“The results show that PPV-06 is well tolerated and confirm the scientific interest in this innovative active immunotherapy approach targeting IL-6. Given the lack of a curative and lasting solution for patients suffering from osteoarthritis, this is an encouraging first step for further clinical development,” said the study’s lead author, François Rannou, MD, PhD, professor of Medicine, University Paris Descartes, Cochin Hospital, Paris, France, in a press release.
Speaking with Medscape’s French edition, Rannou confirmed the launch in 2026 of a multicenter phase 2 trial in seven European countries to evaluate the efficacy of the vaccine approach in 204 patients with inflammatory knee osteoarthritis. “We will initially use the lowest dose, namely 10 µg of PPV-06, which proved in the phase 1 trial to be as immunogenic as the 50-µg dose.”
The effect of immunotherapy on the bone structure was assessed using imaging. “We hope for at least a halt to the deterioration,” Rannou said. If efficacy is confirmed, the vaccination schedule must be defined. “Will it be necessary to vaccinate every year, every 2 years? A phase 2B trial will be necessary to answer this question.”This approach will also be evaluated for other inflammatory diseases, according to Peptinov, the company that developed immunotherapy.
In 2026, additional phase 2 trials will be conducted to evaluate its effectiveness in preventing relapses of giant cell arteritis and Behçet disease and in the treatment of endometriosis. Other conditions, such as uveitis and Takayasu arteritis, are also under consideration.
PPV-06 immunotherapy, developed by Peptinov, targets low-grade chronic inflammation. “Our company has selected indications in which there are unmet medical needs,” stated Peptinov.
Other conditions are under consideration, “such as uveitis and Takayasu arteritis,” an inflammatory disease affecting the aorta and pulmonary arteries.
Since IL-6 is a key cytokine in low-grade inflammatory processes, “these studies will pave the way for an extension of the clinical development of PPV-06 to other indications related to chronic low-grade inflammation, including those associated with ageing,” the laboratory added.
Expectations for progress are high given the long history of setbacks in osteoarthritis research. The development of anti-nerve growth factor monoclonal antibodies, once considered a promising analgesic approach, was halted in 2021 after the discovery of cases of rapid joint destruction.
According to Rannou, “the idea with vaccine immunotherapy is to regulate IL-6, not inhibit it.” IL-6 levels rise only slightly during inflammatory flare-ups of osteoarthritis, which typically last several weeks to 3-6 months.
In contrast, highly inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, and ankylosing spondylitis, involve substantial increases in proinflammatory mediators, and intravenous antibody therapies have shown clear benefits.
“There are now few treatments in clinical trials,” Rannou said. Beyond this vaccine approach, current investigations have assessed GLP-1 receptor agonists for slowing osteoarthritis progression, relieving associated pain, and intraarticular botulinum toxin injections, which have also shown encouraging results.
Given the central role of IL-6 in the pathophysiology of osteoarthritis and cartilage degradation, several trials have previously tested anti-IL-6 antibodies, although none have produced conclusive clinical benefits. In this phase 1 study, we evaluated vaccine-based immunotherapy designed to influence IL-6 levels over the long term.
Immunotherapy uses a conjugate vaccine consisting of a fragment of the IL-6 protein linked to a nontoxic mutant of diphtheria toxoid to generate a neutralizing immune response. Preclinical studies have demonstrated the safety and efficacy of conjugate vaccines.
The phase 1 trial included 24 patients with inflammatory knee osteoarthritis (stage 2 or higher) and ultrasound-confirmed effusion. Participants were randomized to receive 10 µg of PPV-06 (n = 9), 50 µg of PPV-06 (n = 9), or placebo (n = 6). Three injections were administered, with two doses administered 1 month apart and a third dose at week 16. Tolerability was good, with mostly mild-to-moderate adverse events, such as injection site induration, erythema, and headache. No serious adverse events were reported.
Immunotherapy induced an immune response in all treated patients, with anti-IL-6 antibody levels peaking 8 weeks after the third injection and then declining gradually in the absence of a booster dose. No memory T-cell response was detected against the conjugated peptide.
Both treatment groups showed a trend toward improvement in the Knee Osteoarthritis Outcome Score at week 42 compared with the placebo group, particularly for pain and quality of life. This trend was more pronounced in patients with a higher anti-IL-6 neutralising capacity.
Vaccine immunotherapy “seems to have more interest” in diseases characterized by low-grade inflammation, Rannou said. He also noted a potential role in conditions such as diabetes and Alzheimer’s disease, “diseases which are micro-inflammatory.” In these settings, “the levels of inflammation regulation are quite low,” which this vaccination strategy could help address.
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