2025-05-23
Crohn’s Disease: targeting map for better treatment?
Gastroenterology and Hepatology
#CrohnsDisease #CD #MAP #vaccine #vaccination
Crohn’s disease (CD) is a chronic inflammatory condition of the gastrointestinal tract, marked by persistent intestinal inflammation. Its etiology remains poorly understood, resulting from a complex interplay between genetic predisposition, environmental factors, immune dysregulation, and alterations of the gut microbiota. Despite therapeutic advances, the disease remains progressive, recurrent, and incurable. A significant unmet medical need persists, especially for patients with refractory disease or frequent relapses.
Among the pathogenic hypotheses being explored, the involvement of an intracellular infectious agent—particularly Mycobacterium avium subspecies paratuberculosis (MAP)—has regained interest. This mycobacterium has been detected in the intestinal tissues of some CD patients and may trigger or sustain a chronic immune response in genetically predisposed individuals.
In this context, an innovative vaccine-based approach has been explored through the development of two experimental viral-vectored vaccines: ChAdOx2 HAV, based on a non-replicating simian adenoviral vector, and MVA HAV, which uses a modified Ankara poxvirus vector. These vaccines are designed to express four MAP-specific antigens (AhpC, Gsd, p12, mpa), selected for their immunogenic potential.
This study was launched to assess the safety, tolerability, and immunogenicity of these vaccines in patients with active Crohn’s disease. It represents a novel therapeutic vaccination strategy targeting a suspected infectious agent and, if successful, could pave the way for a new approach to Crohn’s disease management.
Twenty-eight adults with mild to moderate Crohn’s disease were enrolled and randomly assigned into five groups. Two groups received a single dose of ChAdOx2 HAV, two other groups received a single dose of MVA HAV, and a fifth group received a prime-boost regimen with ChAdOx2 HAV followed by an MVA HAV booster, eight weeks apart. No participant was on immunosuppressive therapy to preserve the integrity of the immune evaluation.
Vaccines were administered intramuscularly, and patients were followed for 12 to 32 weeks depending on their group. The vaccines were very well tolerated. A total of 196 adverse events were reported—most were mild (76%) or moderate (23%) and resolved within seven days. Only three severe adverse events (grade 3) were observed, with no established link to vaccination. Two serious adverse events (SAEs) were reported, both deemed unrelated to the vaccines.
From an immunological standpoint, the vaccination induced a T-cell response marked by activation of interferon-gamma-producing cells. This response was especially strong in the prime-boost group, where the median cell count rose from 53 to 1,335 after the booster, stabilizing at 544 after two months—suggesting durable immune activation. All four vaccine antigens contributed equally to this response.
Clinically, improvement was observed with a drop in the CDAI score, especially in the high-dose ChAdOx2 and prime-boost groups. In the latter, six out of eight patients achieved a score below 150, corresponding to clinical remission. Similarly, the endoscopic SES-CD score, which measures mucosal inflammation, decreased by more than 50% in four patients, indicating visible mucosal healing.
Crohn’s disease is a chronic inflammatory bowel disorder, currently managed mainly through immunomodulation. Despite therapeutic progress, a significant number of patients experience partial or complete treatment failure, and the exact causes of the disease remain elusive. One persistent hypothesis is the possible involvement of Mycobacterium avium subspecies paratuberculosis, an intracellular pathogen suspected of triggering an abnormal immune response in certain individuals.
Faced with this challenge, this study aimed to test for the first time in humans a therapeutic vaccine targeting MAP, assessing the safety, tolerability, and immunogenicity of the ChAdOx2 HAV and MVA HAV vectors in patients with active Crohn’s disease. It represents an innovative approach, focusing on modulating anti-MAP immunity rather than merely suppressing inflammation.
The results show that both vaccines have a satisfactory safety profile, with good tolerability and strong activation of antigen-specific T cells in the prime-boost group. Clinically, signs of improvement were seen in both the CDAI and endoscopic markers, even though the study was not designed to formally evaluate therapeutic efficacy.
These findings represent a key milestone in the development of a therapeutic vaccine for Crohn’s disease. They warrant further investigation in larger cohorts, incorporating clinical, microbiological, and immunological efficacy endpoints. This approach could potentially lead to a paradigm shift in treatment, by targeting an underlying cause of the disease.
Crohn’s disease (CD) is a chronic inflammatory condition of the gastrointestinal tract, marked by persistent intestinal inflammation. Its etiology remains poorly understood, resulting from a complex interplay between genetic predisposition, environmental factors, immune dysregulation, and alterations of the gut microbiota. Despite therapeutic advances, the disease remains progressive, recurrent, and incurable. A significant unmet medical need persists, especially for patients with refractory disease or frequent relapses.
Among the pathogenic hypotheses being explored, the involvement of an intracellular infectious agent—particularly Mycobacterium avium subspecies paratuberculosis (MAP)—has regained interest. This mycobacterium has been detected in the intestinal tissues of some CD patients and may trigger or sustain a chronic immune response in genetically predisposed individuals.
In this context, an innovative vaccine-based approach has been explored through the development of two experimental viral-vectored vaccines: ChAdOx2 HAV, based on a non-replicating simian adenoviral vector, and MVA HAV, which uses a modified Ankara poxvirus vector. These vaccines are designed to express four MAP-specific antigens (AhpC, Gsd, p12, mpa), selected for their immunogenic potential.
This study was launched to assess the safety, tolerability, and immunogenicity of these vaccines in patients with active Crohn’s disease. It represents a novel therapeutic vaccination strategy targeting a suspected infectious agent and, if successful, could pave the way for a new approach to Crohn’s disease management.
Can a vaccine really calm Crohn’s?
Twenty-eight adults with mild to moderate Crohn’s disease were enrolled and randomly assigned into five groups. Two groups received a single dose of ChAdOx2 HAV, two other groups received a single dose of MVA HAV, and a fifth group received a prime-boost regimen with ChAdOx2 HAV followed by an MVA HAV booster, eight weeks apart. No participant was on immunosuppressive therapy to preserve the integrity of the immune evaluation.
Vaccines were administered intramuscularly, and patients were followed for 12 to 32 weeks depending on their group. The vaccines were very well tolerated. A total of 196 adverse events were reported—most were mild (76%) or moderate (23%) and resolved within seven days. Only three severe adverse events (grade 3) were observed, with no established link to vaccination. Two serious adverse events (SAEs) were reported, both deemed unrelated to the vaccines.
From an immunological standpoint, the vaccination induced a T-cell response marked by activation of interferon-gamma-producing cells. This response was especially strong in the prime-boost group, where the median cell count rose from 53 to 1,335 after the booster, stabilizing at 544 after two months—suggesting durable immune activation. All four vaccine antigens contributed equally to this response.
Clinically, improvement was observed with a drop in the CDAI score, especially in the high-dose ChAdOx2 and prime-boost groups. In the latter, six out of eight patients achieved a score below 150, corresponding to clinical remission. Similarly, the endoscopic SES-CD score, which measures mucosal inflammation, decreased by more than 50% in four patients, indicating visible mucosal healing.
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Toward a new target in Crohn’s disease?
Crohn’s disease is a chronic inflammatory bowel disorder, currently managed mainly through immunomodulation. Despite therapeutic progress, a significant number of patients experience partial or complete treatment failure, and the exact causes of the disease remain elusive. One persistent hypothesis is the possible involvement of Mycobacterium avium subspecies paratuberculosis, an intracellular pathogen suspected of triggering an abnormal immune response in certain individuals.
Faced with this challenge, this study aimed to test for the first time in humans a therapeutic vaccine targeting MAP, assessing the safety, tolerability, and immunogenicity of the ChAdOx2 HAV and MVA HAV vectors in patients with active Crohn’s disease. It represents an innovative approach, focusing on modulating anti-MAP immunity rather than merely suppressing inflammation.
The results show that both vaccines have a satisfactory safety profile, with good tolerability and strong activation of antigen-specific T cells in the prime-boost group. Clinically, signs of improvement were seen in both the CDAI and endoscopic markers, even though the study was not designed to formally evaluate therapeutic efficacy.
These findings represent a key milestone in the development of a therapeutic vaccine for Crohn’s disease. They warrant further investigation in larger cohorts, incorporating clinical, microbiological, and immunological efficacy endpoints. This approach could potentially lead to a paradigm shift in treatment, by targeting an underlying cause of the disease.
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