Phase III, placebo-controlled, randomized, double-blind trial of tableted, therapeutic TB vaccine (V7) containing heat-killed administered daily for one month.

Objective: Immunotherapy of tuberculosis (TB) to shorten treatment duration represents an unmet medical need. Orally delivered, tableted TB vaccine (V7) containing heat-killed (NCTC 11659) has been demonstrated in prior clinical studies to be safe and fast-acting immune adjunct.

Methods: The outcome of Phase III trial of V7 containing 10 µg of hydrolyzed was evaluated in 152 patients randomized at 2:1 ratio: V7 ( = 100), placebo ( = 52).

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

Background: An increasing number of studies is now devoted to immunotherapy of cancer. We evaluated the clinical benefit of hepcortespenlisimut-L (Hepko-V5 [formerly known as V5])-an oral therapeutic vaccine designated by the United States Food and Drug Administration (FDA) as an orphan drug for treatment of hepatocellular carcinoma (HCC). V5 was initially developed by us in 2002 to treat hepatitis B or C viral infections and liver cirrhosis.

Double-blind, placebo-controlled, 1:1 randomized Phase III clinical trial of Immunoxel honey lozenges as an adjunct immunotherapy in 269 patients with pulmonary tuberculosis.

Aim: Safer and shorter antituberculosis treatment (ATT) regimens represent the unmet medical need.

Patients & Methods: The patients were randomly assigned into two arms: the first (n = 137) received once-daily sublingual honey lozenge formulated with botanical immunomodulator Immunoxel and the second (n = 132) received placebo lozenges along with conventional ATT. Immunoxel and placebo arms were demographically similar: 102 versus 106 had drug-susceptible TB; 28 versus 20 multidrug-resistant TB (MDR-TB); 7 versus 7 extensively drug-resistant TB (XDR-TB); and 22 versus 20 TB-HIV.

Randomized, placebo-controlled Phase II trial of heat-killed Mycobacterium vaccae (Immodulon batch) formulated as an oral pill (V7).

Aim: A 1-month Phase II trial was conducted in 41 patients with pulmonary TB who were randomized into treatment (n = 20) and placebo (n = 21) arms to investigate the safety and efficacy of an orally-administered therapeutic TB vaccine (V7) containing 10 µg heat-killed Mycobacterium vaccae provided by Immodulon Therapeutics Ltd (London, UK).

Materials & Methods: Both arms received conventional anti-TB therapy administered along with a daily pill of V7 or placebo. The subject population had four categories of TB: drug-sensitive TB; retreated TB; drug-resistant TB; and TB with HIV distributed in V7 and placebo arms at 9:4:7:6 and 14:1:6:8 ratios, respectively.

Randomized, placebo-controlled phase II trial of heat-killed Mycobacterium vaccae (Longcom batch) formulated as an oral pill (V7).

One-month Phase II trial was conducted in 43 sputum smear-positive patients with pulmonary tuberculosis randomized into treatment (n = 22) and placebo (n = 21) arms to investigate the safety and efficacy of an orally-administered therapeutic TB vaccine (V7) containing 10 μg of heat-killed Mycobacterium vaccae provided by Longcom company. Immunotherapy and control groups comprised 8 newly diagnosed (1stDx TB; 18.6%), 6 re-treated (RTB; 14%), and 29 multidrug-resistant (MDR-TB; 67.

Adjunct immune therapy of first-diagnosed TB, relapsed TB, treatment-failed TB, multidrug-resistant TB and TB/HIV.

Aim: To evaluate the effect of an adjunct immunotherapy in randomized double-blind, placebo-controlled Phase IIb trial involving 123 TB patients.

Methods: Patients were randomly allocated into two arms: one (n = 62) received a once-daily pill of V-5 Immunitor™ (V5) and the other (control; n= 61) received placebo for 30 days in addition to first- or second-line TB drugs administered under directly observed therapy. The subjects in V5 and placebo arms had first-diagnosed, relapsed, treatment-failed and multidrug-resistant TB at ratios of 17:21:11:13 and 20:19:14:8, respectively; among them, ten and seven had HIV coinfection, respectively.

Clinical validation of sublingual formulations of Immunoxel (Dzherelo) as an adjuvant immunotherapy in treatment of TB patients.

Immunoxel (Dzherelo) is a water-alcohol extract of medicinal plants used in Ukraine as an adjunct immunotherapy to TB and HIV therapy. Four types of solid sublingual formulations of Immunoxel were made: sugar dragées, sugar-coated pills, gelatin pastilles and dried-honey lozenges. They were administered once-daily along with TB drugs.

Immune approaches in tuberculosis therapy: a brief overview.

TB is typically caused by Mycobacterium tuberculosis, a symbiotic bacterium present in one-third of the world's population. There any many factors triggering overt clinical disease in a small proportion of humans. In our view the major role in the process is played by the host's immune response, especially self-directed, destructive inflammation.

Phase IIb randomized trial of adjunct immunotherapy in patients with first-diagnosed tuberculosis, relapsed and multi-drug-resistant (MDR) TB.

Placebo-controlled, randomized, phase 2b trial was conducted in 34 adults comprising 18 first-diagnosed (52.9%), 6 relapsed (17.6%), and 10 MDR-TB (29.

Adjunct oral immunotherapy in patients with re-treated, multidrug-resistant or HIV-coinfected TB.

This Phase IIb, placebo-controlled study involved 55 TB patients treated with anti-TB therapy. They were divided into two groups, matched by age, gender, baseline bodyweight and clinical manifestations: one group (n = 27) received a once-daily V-5 Immunitor (V5) immunotherapy pill and the other (n = 28) received placebo. Only one (3.

Safety and efficacy trial of adipose-tissue derived oral preparation V-6 Immunitor (V-6): results of open-label, two-month, follow-up study.

Background: Chronic inflammations, atherosclerosis and obesity, are major risk factors for cardiovascular diseases. Immune modulation of the inflammatory response has shown promise in animal models of atherogenesis and metabolic disease. Tableted dietary supplement, V-6, containing pooled antigens derived from pig adipose tissue has been administered daily to 12 volunteers for 2 months.

Effect of oral immunization with pooled antigens derived from adipose tissue on atherosclerosis and obesity indices.

Modulation of the inflammatory response through vaccination has shown promise in animal models of atherogenesis and obesity-main risk factors for cardiovascular diseases. Tableted preparation, V-6, containing pooled antigens derived from pig adipose tissue was administered per os daily to 13 volunteers for 3 months. Total cholesterol and LDL levels have not changed from the baseline value; 193.

Clinical experience with therapeutic vaccines designed for patients with hepatitis.

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.

Serodeconversion of HIV antibody-positive AIDS patients following treatment with V-1 Immunitor.

It is extremely rare when HIV seropositive adult patients experience spontaneous loss of antibodies, that is, seroreversion. The disappearance of HIV antibodies was occasionally attributed to iatrogenic intervention-serodeconversion. Such interventions include: HAART; oral interferon; Chinese herbal remedies; and therapeutic AIDS vaccines derived from pooled blood.

Open-label trial of therapeutic immunization with oral V-5 Immunitor (V5) vaccine in patients with chronic hepatitis C.

We evaluated whether V-5 Immunitor (V5)--tableted therapeutic bivalent vaccine comprising heat-inactivated HCV antigens from pooled blood of HBV- and HCV-infected donors - may produce clinical benefit through induction of oral tolerance and reduction of immune-mediated liver injury. Once daily dose of V5 was administered per os to 10 patients with chronic hepatitis C in an open-label study that lasted 1 month. Every patient who entered the study had elevated liver enzyme levels, which at the end of study have decreased in 100% of analyzed patients.

Oral vaccination: where we are?

As early as 900 years ago, the Bedouins of the Negev desert were reported to kill a rabid dog, roast its liver and feed it to a dog-bitten person for three to five days according to the size and number of bites [1] . In sixteenth century China, physicians routinely prescribed pills made from the fleas collected from sick cows, which purportedly prevented smallpox. One may dismiss the wisdom of the Bedouins or Chinese but the Nobel laureate, Charles Richet, demonstrated in 1900 that feeding raw meat can cure tuberculous dogs - an approach he termed zomotherapy.

Prolonged survival of end-stage AIDS patients immunized with therapeutic HIV vaccine V-1 Immunitor.

Death, rather than surrogate markers, is a single and most straightforward clinical endpoint, defining unequivocally the merit of a therapeutic intervention. As there is still neither a cure for AIDS nor a vaccine to prevent HIV infection, an AIDS diagnosis remains associated with a death sentence. V-1 Immunitor (V1) is an experimental, oral, therapeutic AIDS vaccine licensed as a dietary supplement.

Autoimmunity, alloimmunization and immunotherapy of AIDS.

The nature of clinical and physiological manifestations associated with HIV infection suggests that AIDS is an autoimmune disease. The conventional immunotherapeutic approaches aimed at enhancing the immune response against HIV have repeatedly failed when applied in the clinical practice. The results of several dozen therapeutic AIDS vaccine trials have consistently shown that while in vitro measured HIV-specific immune responses were evident as a result of vaccination the clinical improvement has been seldom observed.

Clinical experience with therapeutic AIDS vaccines.

Recently, there has been a renewed interest in therapeutic vaccination as an adjunct or alternative to current treatment options for HIV. The first immunotherapeutic trial relevant to this topic was published in 1983. Since then, several dozen therapeutic vaccine trials have been carried out.

[AIDS vaccines and immunotherapy of infertility].

The development of prophylactic AIDS vaccines and immunotherapeutic approaches such as therapeutic AIDS vaccines would greatly benefit from acquired experience in reproductive immunology field relating to pregnancy and infertility. Certain immune and pathological aspects of HIV infection are closely related to problems faced by obstetricians, embryologists, gynecologists, and andrologists. This review attempts to bring together the recent advances in AIDS field with progress made in the physiology and pathology of reproduction in humans.

Phase II placebo-controlled study of V-1 Immunitor as a therapeutic modality for treatment of HIV.

Background: V-1 Immunitor (V1) is an oral AIDS vaccine containing heat- and chemically-inactivated viral antigens derived from pooled blood of HIV-positive donors. V1 has a pending status as an investigational drug but is currently marketed as a dietary supplement. Earlier published, uncontrolled studies of V1 demonstrated body weight gain, increase in T-lymphocyte numbers, decrease in viral load, and improved survival of end-stage AIDS patients.

Mucosal AIDS vaccines.

Debates are still being waged over what is the best strategy for developing a potent AIDS vaccine. All the obvious approaches to making AIDS vaccines have been tried in the past two decades without much success. It is clear that new thinking and a revision of prevailing dogmas needs to be in place if we really want a vaccine.

Low-cost anti-HIV compounds: potential application for AIDS therapy in developing countries.

A considerable progress has been made in recent years in the field of drug development against HIV. However, the current cost of AIDS drugs is the main obstacle that prevents their use in developing countries, where 95% of HIV-infected patients reside. The average yearly price of AIDS therapy and related health care of affected patients in the USA runs as high as $22,000 - an amount that corresponds to the combined income of as many as one hundred individuals in developing countries.