Transfer Factor Preparations Research Articles

Protective activity of specific transfer factor against Salmonella typhimurium infection

Specific transfer factor (TF) extracted from spleens of sensitized and non-sensitized guinea pigs to study the efficacy of transfer of cellular immunity specific for salmonella . Two groups each of five guinea pigs were used for in vivo TF preparation. The First group was inoculated with 1 ml of aromatic dependent Salmonella typhimurium SL 1479 vaccine at a dose of 10' cfu/ml intramuscularly twice at two weeks intervals. The second group was injected with trypticase soy broth similarly . These two groups used as a donor for TF, and TFn respectively. Twenty one recipient guinea pigs were divided into three groups, the first group was TF at a dose of 1 ml equivalent to 5X10 cell intramuscularly three times/2 days intervals, Similarly the second group was given TF, where as the third group was given PBS- Cell mediated immunity in recipient animal was evaluated by delayed type hypersensitivity - skin test, Macrophage migration inhibition test (MIF) and then challenged with virulent Salmonella typhimurium. The TFt recipient group induced skin test and showed migration indices less than 0.8 and overcome the challenge organism. Contrary to TFn & PBS recipient groups which did not show any response for skin test and given migration indices more than 0.8 and did not show resistance for virulent Salmonella typhimurium .

Experimental study on thermal analysis of helical coil heat exchanger using Green synthesis silver nanofluid

Abstract Green Synthesis of silver nano particles using Neem leaf extracts and preparation of nanofluid, heat transfer, pressure drop and friction factor for helical coil heat exchanger have been experimentally investigated and compared with the standard correlation given by various researchers is discussed in this paper. Inlet temperatures of hot water on coil side and cold water on shell side were maintained at around 58 °C and 32 °C respectively. Experiments were performed over the Dean number range on shell side is 1000 to 3000, by varying mass flow rate and Reynolds number on coil side is kept constant at 5780. Thermal analysis has been carried out by considering various parameters such as temperature, flow rate, overall heat transfer coefficient. Use of green synthesized Nano particles have shown enhancement of 32% in heat transfer coefficient compared to base fluid. Thermal performance factor has been slightly decreased with increase in concentration and is feasible to use 0.05% of concentration nanofluid.

Obstacles and limitations of transfer factor biological activity assay design.

Transfer factor (TF) is a heterogeneous mix of low-molecular weight molecules obtained from dialyzed leukocyte extract that is capable of transferring cell-mediated immunity. As an immunostimulatory drug TF is used to improve treatment of infectious diseases, allergies, cancer and immune deficiencies. The main benefit of TF preparations as immunotherapeutic agents is the induction of a rapid immune response and the potential of TF as an adjuvant in combination with other drugs might lead to development of novel approaches to combat various diseases in the future. The process of TF preparation is rather simple. However, with respect to fact that TF is composed by several multifunction molecules, it is likely that during the activity measurement based only on one single parameter, other TF biological activities might be overlooked. In addition, separated TF components might display synergetic activity effect. According to recent European Pharmacopoeia there is no general protocol for immuno-stimulatory drugs (including TF) activity measurement available. Nevertheless, for the process of TF preparation, control of input material and for final pharmaceutical product batches it is inevitable to guaranty proper quality control including appropriate in vivo or in vitro test(s) for TF biological activity assay. The animal-origin materials and in vivo assays convey a considerable logistic, ethic and economic problem, meanwhile the available in vitro assays have been reported with limited reproducibility and sometimes contradictory results. The currently used method for testing biological activity of TF is the in vitro MTT cells proliferation assay that is recognized by control authorities in Slovak Republic. Keywords: immune system; transfer factor; dialysable leukocyte extract; diseases; MTT cells proliferation assay.

Неспецифічні та антигенспецифічні властивості трансфер-фактора, отриманого з молозива сенсибілізованих до збудника сальмонельозу корів

A promising direction for the treatment and prevention of many animal diseases caused by viruses, bacteria and other infectious agents is transfer factor usage. The article presents new data on the study of nonspecific and antigen-specific properties of transfer factor derived from bovine colostrum. Colostrum from immunized cows of black-and-white breed was used in order to obtain transfer factor. To sensitize the animals of experimental group, the vaccine was administered to cows twice at doses of 10 cm3 and 15 cm3 in 1.5 months before parturition. Animals of the control group were given an appropriate amount of physiological saline solution. The concentrated vaccine against Salmonellosis in calves from the Kherson Biofactory was used for immunization. To determine the presence of sensitization to Salmonella agent, an allergic skin test was used in 14 days after immunization. Colostrum samples were taken immediately and in 2 days after parturition of cows. Isolation of the transfer factor preparations from colostrum was carried out according to the method modified by the Department of Microbiology, Virology and Biotechnology of NUBIP of Ukraine. In order to assess the ability of transfer factor derived from vaccinated cows’ donors to transfer the condition of specific sensitization, a leukocyte migration inhibition test was made by G. Freemel method with the use of transfer factor in different dilutions. To do this, a leukocytes suspension from mice spleen that was previously incubated with different dilution of the studied preparation with the addition of a specific antigen was used. The results of studies have shown that transfer factor obtained from colostrum in cows, sensitized to the salmonellosis pathogen, has pronounced antigen-specific properties against the Salmonella dublin. In addition, it is established that the antigen-specific properties of transfer factor depend on the degree of its dilution. Thus, transfer factor obtained from the colostrum can be used to transfer cell-mediated immunity into other animals to diseases against which pathogens the animals donors are immunized

The Effect of Transfer Factor as Immunoprotective in Mice Challenged with <i>Mycobacteriu</i>m <i>tuberculosis</i>

Background: Transfer Factor (TF) is an immune modulator which stimulates the cellular arm of the immune system (killer lymphocytes), activates immune cytokine synthesis and regulates immune function [1]. TF is very effective in those diseases in which CMI plays a relevant role in protection and control of the disease, such as intracellular bacterial diseases (tuberculosis) [2]. TF are low molecular weight products from immune cells that are able to transmit the ability to express delayed-type hypersensitivity (DTH) and cell mediated immunity (CMI) from sensitized donors to non immune recipients [3]. Objectives: The aim of this experimental study is to determine the protective efficacy of transfer factor (TF) as immunotprotective for mice. Materials and methods: A total number of 82 mice were examined for their immunopotency and protective efficacy of Transfer factor (TF) against challenge dose of M. tuberculosis (107 CFU). A number of 20 mice were immunized with the attenuated strain of M. bovis, Bacillus Calmette-Guerin (BCG). After 21 days of BCG spleens of 10 tuberculous mice were removed aseptically for the preparation of TF. To evaluate the effect of TF 3 groups of inbred BALB/c male mice were injected with TF and challenged with virulent M. tuberculosis, All mice with TF were tested for tuberculin skin test (TST) so as to determine susceptibility and resistance against tuberculosis, susceptible groups of mice were challenged with virulent M. tuberculosis.Followed by study of humoral response by immunization of a group of mice with immune sera and challenged with M. tuberculosis H37Rv strain. Followed by an experiment of group A and B for the susceptibility and resistance of the strains of mice. Results: After three weeks of observations the mice of experiment were tested for tuberculin skin test and the results were positive. Effectiveness determination of TF as protective efficacy was (83.3%). Humoral immunity response against M. tuberculosis showed negative reaction hence mortality rate was 100%, group B mice were resistant for BCG (Swiss white strain). Conclusions: The results indicated that administration of murine transfer factor (mTF) extracted and prepared from spleen of animal model (mice) as immunoprotective for challenged mice of M. tuberculosis (H37Rv) showed a better results enhanced immune response in respect to delayed type hypersensitivity, survival rate and mortality rate suggesting that efficacy of mTF as immunotherapy for tuberculosis.

The effect of Transfer Factor as Immunotherapy comparing with the effect of BCG in Mice challenged with Mycobacterium tuberculosis

Background: Transfer Factor (TF) is an immune modulator which stimulates the cellular arm of the immune system (killer lymphocytes), activates immune cytokine synthesis and regulates immune function (Lawrence, 1955).TF is very effective in those diseases in which CMI plays a relevant role in protection and control of the disease, such as intracellular bacterial diseases (tuberculosis). ( Estrada Parra, et al1955). TF are low molecular weight products from immune cells that are able to transmit the ability to express delayed-type hypersensitivity (DTH) and cell mediated immunity (CMI) from sensitized donors to non immune recipients (Kirkpatrick, 2000). Objectives: The aim of this experimental study is to determine the protective efficacy of transfer factor (TF) as immunotherapy for mice in comparison to BCG. Materials and methods: A total number of 102 mice were examined for their immunopotency and protective efficacy of Transfer factor (TF) comparing to the protective efficacy of BCG single and second repeated dose against challenge dose of M. tuberculosis (107 CFU) . A number of 20 mice were immunize with the attenuated strain of M. bovis, Bacillus Calmette-Guerin (BCG). After 21 days of BCG spleens of 10 tuberculous mice were removed aseptically for the preparation of TF. To evaluate the effect of TF 3 groups of inbred BALB/c male mice were injected with TF and challenged with virulent M. tuberculosis, followed by another 3 groups of inbred BALB/c male mice which were immunized with BCG single and second repeated dose. All mice with BCG and TF were tested for tuberculin skin test (TST) so as to determine susceptibility and resistance against tuberculosis, susceptible groups of mice were challenged with virulent M. tuberculosis. Followed by study of humoral response by immunization of a group of mice with immune serum and challenged with M. tuberculosis H37Rv strain. Followed by an experiment of group A and B for the susceptibility and resistance of the strains of mice. A group of dead mice For histological study of the infected lungs were examined. Results:After three weeks of observations the mice of experiment(1) were tested for tuberculin skin test and the results were positive. Effectiveness determination of TF as protective efficacy was (83.3%). while effectiveness determination and protective efficacy of BCG first dose and boosting dose were (50%) and (70%) respectively. Humoral immunity response against M. tuberculosis showed negative reaction hence mortality rate was 100%, group B mice were resistant for BCG (Swiss white strain) and the results of histological study of the infected lungs showed lung bacilli that was M. tuberculosis. Conclusions: The results indicated that administration of murine transfer factor (mTF) extracted and prepared from spleen of animal model (mice) as immunotherapy for challenged mice of MTB (H37Rv) showed a better results enhanced immune response in respect to delayed type hypersensitivity , survival rate and mortality rate suggesting that efficacy of mTF as immunotherapy for tuberculosis. Repeat dose of BCG enhanced immune response in respect to delayed type hypersensitivity , survival rate (70%) and mortality rate (30%), suggesting that efficacy of BCG vaccine may improve and give better results if booster doses are given.

Cell mediated immunity to meet the avian influenza A (H5N1) challenge

Avian influenza A subtype H5N1 virus with its recombination potential with the human influenza viruses presents a threat of producing a pandemic. The consensus is that the occurrence of such a pandemic is only a matter of time. This is of great concern, since no effective vaccine is available or can be made before the occurrence of the event. We present arguments for the use of cell mediated immunity for the prevention of the infection as well as for the treatment of infected patients. Transfer factor (TF), an immunomodulator of low molecular weight capable of transferring antigen-specific cell mediated immune information to T-lymphocytes, has been used successfully over the past quarter of a century for treating viral, parasitic, and fungal infections, as well as immunodeficiencies, neoplasias, allergies and autoimmune diseases. Moreover, several observations suggest that it can be utilised for prevention, transferring immunity prior to infection. Because it is derived from lymphocytes of immune donors, it has the potential to answer the challenge of unknown or ill-defined pathogens. Indeed, it is possible to obtain an antigen-specific TF preparation to a new pathogen before its identification. Thus, a specific TF to a new influenza virus can be made swiftly and used for prevention as well as for the treatment of infected patients.

Transfer Factors: Identification of Conserved Sequences in Transfer Factor Molecules

Transfer factors are small proteins that "transfer" the ability to express cell-mediated immunity from immune donors to non-immune recipients. We developed a process for purifying specific transfer factors to apparent homogeneity. This allowed us to separate individual transfer factors from mixtures containing several transfer factors and to demonstrate the antigen-specificity of transfer factors. Transfer factors have been shown to be an effective means for correction of deficient cellular immunity in patients with opportunistic infections, such as candidiasis or recurrent Herpes simplex and to provide prophylactic immunity against varicella-zoster in patients with acute leukemia. Transfer factors of bovine and murine origin were purified by affinity chromatography and high performance liquid chromatography. Cyanogen bromide digests were sequenced. The properties of an apparently conserved sequence on expression of delayed-type hypersensitivity by transfer factor recipients were assessed. A novel amino acid sequence, LLYAQDL/VEDN, was identified in each of seven transfer factor preparations. These peptides would not transfer expression of delayed-type hypersensitivity to recipients, which indicates that they are not sufficient for expression of the specificity or immunological properties of native transfer factors. However, administration of the peptides to recipients of native transfer factors blocked expression of delayed-type hypersensitivity by the recipients. The peptides were not immunosuppressive. These findings suggest that the peptides may represent the portion of transfer factors that binds to the "target cells" for transfer factors. Identification of these cells will be helpful in defining the mechanisms of action of transfer factors.

The influence of age on transfer factor treatment of cellular immunodeficiency, chronic fatigue syndrome and/or chronic viral infections

A group of 222 patients suffering from cellular immunodeficiency (CID), frequently combined with chronic fatigue syndrome (CFS) and/or chronic viral infections by Epstein-Barr virus (EBV) and/or cytomegalovirus (CMV), were immunologically investigated and treated with transfer factor (TF). The age range was 17-77 years. In order to elucidate the influence of aging on the course of the disease and on treatment, 3 subgroups were formed: 17-43 years, 44-53 years, and 54-77 years. Six injections of Immodin (commercial preparation of TF by SEVAC, Prague) were given in the course of 8 weeks. When active viral infection was present, IgG injections and vitamins were added. Immunological investigation was performed before the start of therapy, and subsequently according to need, but not later than after 3 months. The percentages of failures to improve clinical status of patients were in the individual subgroups, respectively: 10.6%, 11.5% and 28.9%. The influence of increasing age on the percentage of failures to normalize low numbers of T cells was very evident: 10.6%, 21.2% and 59.6%. In individuals uneffected by therapy, persistent absolute lymphocyte numbers below 1,200 cells were found in 23.1%, 54.5% and 89.3% in the oldest group. Statistical analysis by Pearson's Chi-square test, and the test for linear trend proved that the differences among the individual age groups were significant. Neither sex, nor other factors seemed to influence the results. The results of this pilot study show that age substantially influences the failure rate of CID treatment using TF. In older people, it is easier to improve the clinical condition than CID: this may be related to the diminished number of lymphocytes, however, a placebo effect cannot be totally excluded.

Murine Transfer Factors: Dose-Response Relationships and Routes of Administration

Transfer factors are protein immunomodulators that transfer the ability to express cell-mediated immunity from immunized donors to nonimmune recipients. The effects are antigen-specific. The experiments described in this report are a comparison of the relationship of the route of administration of various transfer factors to the magnitude of the delayed hypersensitivity responses (footpad swelling) to the corresponding antigen in the recipients. Three doses of each of four affinity-purified transfer factor preparations were studied. There were no significant differences in the footpad responses by recipients of either oral or subcutaneous transfer factor. These results support proposals for oral administration of transfer factors in clinical trials.

Effect of Brucella abortus transfer factor in preventing murine brucellosis

Mice vaccinated with a protein extract of attenuated Brucella abortus strain 19 had increased resistance to infection with virulent B. abortus strain 2308 and had increased antibody responses to strain 2308. However, resistance to infection and antibody responses were not increased when nonvaccinated recipient mice were given transfer factor preparations that were obtained from either vaccinated donor mice or strain 2308-infected donor mice. Vaccination of mice with the strain 19 extract plus treatment with each transfer factor preparation also did not further increase resistance to infection or antibody responses when compared with mice that received the vaccine alone. These results suggest that transfer factor from mice that have either vaccine-induced protective immunity to B. abortus or active B. abortus infections does not enhance antibody responses and resistance to infection with B. abortus.

Effect of Brucella abortus transfer factor in preventing murine brucellosis.

Mice vaccinated with a protein extract of attenuated Brucella abortus strain 19 had increased resistance to infection with virulent B. abortus strain 2308 and had increased antibody responses to strain 2308. However, resistance to infection and antibody responses were not increased when nonvaccinated recipient mice were given transfer factor preparations that were obtained from either vaccinated donor mice or strain 2308-infected donor mice. Vaccination of mice with the strain 19 extract plus treatment with each transfer factor preparation also did not further increase resistance to infection or antibody responses when compared with mice that received the vaccine alone. These results suggest that transfer factor from mice that have either vaccine-induced protective immunity to B. abortus or active B. abortus infections does not enhance antibody responses and resistance to infection with B. abortus.

Adoptive Transfer of Delayed Hypersensitivity and Protective Immunity to Eimeria tenella with Chicken-Derived Transfer Factor

Delayed hypersensitivity (DH) and protective immunity were transferred to nonimmune 4- and 10-week-old broiler chickens with transfer factor (TF) prepared from splenic leukocytes of chickens immunized with CocciVac® D. Only chickens injected with the immune TF showed DH by wattle reaction to oocyst antigen and protective immunity to Eimeria tenella challenge infection. Chickens given a single injection of TF 5 days before challenge infection exhibited a significant (P<.05) DH response at the time of infection. Immune TF preparations were active at concentrations of 100, 200, or 400 mg. Neither DH nor protective immunity was transferred to chickens injected with the TF-diluent control or nonimmune TF. The nonimmune TF was prepared from chickens kept free of coccidial infection. These findings indicated that TF prophylaxis produced beneficial results in nonimmune chickens by conferring some protection against challenge with E. tenella. The effects of TF on T-lymphocyte mediated protective immunity to coccidia in chickens are discussed.

A case report of the successful treatment of recurrent aphthous stomatitis with some preparations of orally administered transfer factor

A patient with severe disabling recurrent aphthous stomatitis (RAS) was treated with four different preparations of oral human transfer factor (TF), as well as placebo, following a doubleblind protocol. Two of the TF preparations had a significant effect upon the course of the patient's illness by prolonging the interval between attacks and decreasing the severity of attacks. No side effects attributable to any of the preparations were noted by the patient. Thus, some but not all preparations of human transfer factor given orally are an effective therapy for RAS.

Transfer of Salmonella resistance and delayed hypersensitivity with murine-derived transfer factor.

Protective host immunity and delayed hypersensitivity were transferred to nonimmune ICR and C3H/HeJ mice with transfer factor prepared from the splenic lymphocytes of ICR Swiss mice immune to Salmonella typhimurium. Only mice injected with the "immune" dialysate exhibited significant footpad swelling (P less than 0.01) to a spent medium antigen of S. typhimurium, but not Listeria monocytogenes. Host survival to a lethal Salmonella challenge infection was seen only in transfer factor-injected mice. Also, these challenged animals had fewer numbers of bacteria present in their spleens (P less than 0.01) than did challenged mice previously injected with either control dialysates or commercial endotoxin. Neither the Salmonella antigens nor endotoxin present in the sterile transfer factor preparation was responsible for the transfer of host protection and delayed hypersensitivity, since none of the control dialysates resulted in any positive responses when injected into either the ICR Swiss or endotoxin-resistant C3H/HeJ mice.

Passive transfer of immunity to trichostrongyle species infections in sheep. Investigations of specificity and limitations of 'transfer factor' activity with Trichostrongylus axei infections.

The ability of transfer factor (TF) preparations to transfer resistance to challenge with Trichostrongylus axei in sheep and to correct partially the immune immaturity of young lambs was confirmed. Non-dialysed TF consistently transferred resistance but dialysed TF frequently failed, perhaps demonstrating a loss of activity during TF preparation procedures. Specificity of transfer was demonstrated when T. axei TF transferred resistance to T. axei challenge but Haemonchus contortus TF failed to do so.

Preparation, properties, and clinical use of human transfer factor and “immune” RNA

Preparation, properties, and clinical use of human transfer factor and “immune” RNA

Progressive vaccinia: immunological aspects and transfer factor therapy.

Progressive vaccinia is a rare and serious complication of smallpox vaccination. Depressed immune function can generally be found as an underlying disorder; thus adequate immuno-correction may be expected to be therapeutically effective. Humoral and cell-mediated immunity was repeatedly examined in one case throughout the course of the disease. Results indicated partial deficiency of cell-mediated immunity. No therapeutic effect was achieved by using human antivaccinia immunoglobulin and N-methylisatin beta-thiosemicarbazone. Transfer factor therapy was also attempted. Treatment with a non-specific transfer factor preparation was followed by a transitory clinical improvement. A specific transfer factor preparation given during the last month of life, however, had no therapeutic effect. The patient died on the 145th day after vaccination. Autopsy findings pointed to combined immune deficiency.

Skin test conversion following transfer factor A double-blinded study of normal individuals

The use of skin test conversion as a measure of change in cellular immune status is a fairly routine procedure despite considerable potential for variation in testing. This study is a double-blinded and randomized reassessment of this assay in the context of transfer factor (TF) activity. Thirty-three normal people with negative tuberculin skin tests received either dialyzable TF, column purified TF, hypoxanthine, or saline in a randomized and double-blinded fashion. Skin test reactivity to tuberculin and keyhole limpet hemocyanin (KLH) was read by three of the investigators. Nine of 20 recipients of TF and 7 of 13 controls demonstrated an increase in tuberculin reactivity after “transfer.” Four reactions were greater than 10 mm. Fourteen of 20 recipients of TF and 7 of 13 controls demonstrated some reactivity to KLH on initial testing post-transfer. Control solutions were as effective as TF preparations in “causing” skin test conversion. These observations stress the importance of controlled and blinded studies when serial skin test reactivity is used to evaluate cellular immune status in humans.

The effect of transfer factor on lymphocyte transformation. Comparison of augmentation by dialysates of leucocytes and lymphoid and non-lymphoid organs.

In this paper we describe experiments to determine whether dialysable extracts of non-lymphoid and lymphoid organs augment lymphocyte transformation in vitro in a manner similar to the augmenting activity of leucocyte dialysates. Human peripheral blood leucocytes were cultured with tuberculin PPD or leucoagglutinin, and dose-related effects of the dialysable extracts on lymphocyte transformation were studied by 125IUdR incorporation. Augmentation of lymphocyte transformation was obtained not only with leucocyte dialysates but also with dialysable extracts of lymphoid and non-lymphoid organs (e.g. spleen, liver, kidney, brain). It is concluded that the agent or agents present in dialysable leucocyte transfer factor preparations, which augment lymphoid transformation in vitro, are widely distributed throughout mammalian tissues.