Clinical Experience with Therapeutic Vaccines Designed for Patients with Hepatitis

Abstract

Franciscan missionary Giovanni Di Plano Carpini traveled in 1245 to a country named Yeke Tartar, to visit a certain man called Genghis Khan. His journey's report narrated peculiar dietary habits of the locals: "they eat anything, even lice". Little that Carpini knew, he had actually documented the earliest known to us record of oral vaccination against blood-borne infections - an approach that is still used occasionally in the present-day Mongolia for therapy of hepatitis. Currently, efforts aimed at developing therapeutic hepatitis vaccines have switched to more palatable path, but we may still benefit from the insight of medieval Mongols. This review provides an update on development of hepatitis B and C vaccines as related to immunotherapy of hepatitis. Immune therapy is a fast-moving field but the results so far failed to pitch woo. Current trends in research on therapeutic vaccine candidates and liver immunology are discussed. We subscribe to the idea that viral hepatitis is essentially an autoimmune disease generating immune-mediated liver damage. Therapeutic vaccines need to be designed in such a way that self-destructive immunity of the host is targeted not the virus, which is not cytopathic.

Open-label phase II clinical trial in 75 patients with advanced hepatocellular carcinoma receiving daily dose of tableted liver cancer vaccine, hepcortespenlisimut-L

“…Judging from our preliminary in vitro investigations, physiologically relevant doses of V5 produce within 2 days a potent anti-inflammatory response reflected in a 10-fold decrease of key inflammatory cytokine tumor necrosis factor-α and at the same time manifold increase in frequency of interferon-γ secreting CD4 and CD8 T cells expressing proliferation markers Ki-67 and CD69 (unpublished, 2010). V5 has been extensively used by us to treat hepatitis and tuberculosis—2 diseases that have in common with HCC only one underlying characteristic—the inflammatory immune reaction directed against self 22–25,44…”

“…The founding principle for making V5 is not much different from established practice of manufacturing old-fashioned killed vaccines, eg, hepatitis B vaccine made from pooled plasma. The process of manufacturing is described in detail – it involves heat and chemical inactivation with subsequent formulation into a tablet capable to withstand digestive degradation in the stomach 22. The manufacturing process eliminates potentially infectious hepatitis B and C viruses as evidenced by serology and PCR analysis of the tablets.…”

“…The accumulated clinical experience in over 10,000 patients in about 30 additional countries indicates that V5 is safe and effective for a range of clinical indications. Published clinical trials have shown the outstanding safety and beneficial effect of V5 in patients with chronic viral hepatitis and liver cirrhosis 22–25. V5 is a tableted, off-shelf formulation derived from heat-inactivated, hydrolyzed, pooled blood of hepatitis B and C carriers, prepared according to proprietary technology developed by us back in 2002 22…”

Immunomodulation and infection: back to the future

“…Empirical immunotherapy has long preceded the knowledge of the immune system, and sometimes what is discovered in the 'past' can be the 'prologue' to future discoveries [1]. Immunotherapy in TB [10] or oral vaccination against blood-borne infections [16] have been recorded in history, and knowledge of this history can guide us in the future. "Immunotherapy in TB or oral vaccination against blood-borne infections have been recorded in history, and knowledge of this history can guide us in the future.…”

Editorial [Hot Topic: New Developments in Drug and Vaccine Discoveries (Executive Editor: Aldar S. Bourinbaiar)]

“…The team of Batdelger et al [1] from Mongolia, Thailand and USA, review the current trend in therapeutic vaccines and summarize their own contribution to immunotherapy of hepatitis B and C -two most common serious, infectious diseases that affect globally over 500 million people or roughly 10% of global population.…”