Abstracts on Key Studies Conducted with
Transfer Factor from Bovine Colostrum
novo initiation of specific cell-mediated immune responsiveness in
chickens by transfer factor (specific immunity inducer) obtained from
bovine colostrum and milk.
Acta Virol 1988 Jan;32(1):6-18
Wilson GB, Poindexter C, Fort JD, Ludden KD.
Amtron, Inc., Charleston, South Carolina.
Transfer factors (TF) were prepared from colostrum and milk of bovines
previously immunized with antigens obtained from Coccidioides immitis,
infectious bovine rhinotracheitis virus, or from the viral agents responsible
for avian Newcastle disease, laryngotracheitis disease or infectious bursal
disease. The ability of bovine TF to transfer specific cell-mediated immune
responsiveness to a markedly xenogenic species was studied using specific
pathogen free (SPF) and standard commercial (SC) chickens as model recipients.
Cell-mediated immune responsiveness was documented using one or more of the
following for each antigen (organism) studied: (a) an in vitro chicken leukocyte
(heterophil) migration inhibition assay; (b) delayed-wattle reactivity; or (c)
protection from clinical disease. Chicken TFs obtained from spleens of immune
donors were evaluated in parallel to bovine TF's in selected comparative
studies. Bovine TF also referred to as specific immunity inducer (SII), and
chicken TF were found to initiate antigen-specific cell-mediated immunity de
novo in previously non-immune SPF chickens as well as in SC chickens despite the
presence of maternally acquired humoral antibody which may serve as a
"barrier" to immunization of SC chickens when commercially available
vaccines are administered by parenteral routes. Bovine TF's specific for
laryngotracheitis virus or infectious bursal disease virus afforded protection
equal to that found for commercially available vaccines. Bovine TF's action was
rapid (less than a day) and of relatively long duration at least 35 days.
hypersensitivity responses induced by bovine colostral components.
Am J Vet Res 1985 Apr;46(4):875-8
Radosevich JK, Scott GH, Olson GB.
Transfer factor-type substances obtained from leukocytic cells and fluid
portions of bovine colostrum caused effective passive transfer of delayed-type
hypersensitivity responses across species barriers. Passive transfer of Brucella
abortus sensitivity was obtained with equal regularity when using components
derived from peripheral blood and colostrum of dams sensitized at 3 and 9 months
of age. Colostral feedings to calves caused the passive transfer of delayed-type
hypersensitivity as early as 2 days after parturition. The findings indicated
that colostral components were important in the process of cell-mediated
from a pilot study of transfer factor in chronic fatigue syndrome.
De Vinci C, Levine PH, Pizza G, Fudenberg HH, Orens P, Pearson G, Viza D.
Immunodiagnosis and Immunotherapy Unit, 1st Division of Urology
Sant'Orsola-Malpighi Hospital, Bologna, Italy.
Transfer Factor (TF) was used in a placebo controlled pilot study of 20
patients with chronic fatigue syndrome (CFS). Efficacy of the treatment was
evaluated by clinical monitoring and testing for antibodies to Epstein-Barr
virus (EBV) and human herpes virus-6 (HHV-6). Of the 20 patients in the
placebo-controlled trial, improvement was observed in 12 patients, generally
within 3-6 weeks of beginning treatment. Herpes virus serology seldom correlated
with clinical response. This study provided experience with oral TF, useful in
designing a larger placebo-controlled clinical trial.
Randomized controlled trial
of transfer factor for the treatment of recurrent non-bacterial female
cystitis (NBRC): a preliminary report.
De Vinci C, Pizza G, Cuzzocrea D, Menniti D, Aiello E, Maver P, Corrado G,
Romagnoli P, Dragoni E, LoConte G, Riolo U, Masi M, Severini G, Fornarola V,
Immunodiagnosis and Immunotherapy Unit, 1st-Division of Urology, Bologna,
Results of conventional treatment of female non-bacterial recurrent cystitis
(NBRC) are discouraging. Most patients show an unexpected high incidence of
vaginal candidiasis, while their cell mediated immunity to Herpes simplex
viruses (HSV) and Candida antigens seems impaired, and it is known that the
persistence of mucocutaneous chronic candidiasis is mainly due to a selective
defect of CMI to Candida antigens. Twenty nine women suffering of NBRC, and in
whom previous treatment with antibiotics and non-steroid anti-inflammatory drugs
was unsuccessful, underwent oral transfer factor (TF) therapy. TF specific to
Candida and/or to HSV was administered bi-weekly for the first 2 weeks, and then
once a week for the following 6 months. No side effects were observed during
treatment. The total observation period of our cohort was 24379 days with 353
episodes of cystitis recorded and a cumulative relapse index (RI) of 43. The
observation period during and after treatment was 13920 days with 108 relapses
and a cumulative RI of 23 (P < 0.0001). It, thus, seems that specific TF may
be capable of controlling NBRC and alleviate the symptoms.
factors: identification of conserved sequences in transfer factor
Mol Med 2000 Apr;6(4):332-41
Department of Medicine, University of Colorado Health Sciences Center,
BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
of anti HHV-6 transfer factor for the treatment of two patients with
chronic fatigue syndrome (CFS). Two case reports.
Ablashi DV, Levine PH, De Vinci C, Whitman JE Jr, Pizza G, Viza D.
Advanced Biotechnologies Inc., Columbia, MD 21046, USA.
Specific Human Herpes virus-6 (HHV-6) transfer factor (TF) preparation,
administered to two chronic fatigue syndrome patients, inhibited the HHV-6
infection. Prior to treatment, both patients exhibited an activated HHV-6
infection. TF treatment significantly improved the clinical manifestations of
CFS in one patient who resumed normal duties within weeks, whereas no clinical
improvement was observed in the second patient. It is concluded that HHV-6
specific TF may be of significant value in controlling HHV-6 infection and
of transfer factor in treating patients with recurrent ocular herpes
Meduri R, Campos E, Scorolli L, De Vinci C, Pizza G, Viza D.
Eye Physiopathology Clinical Service, University of Bologna, Italy.
Recurrent ocular herpes is an insoluble problem for the clinician. As
cellular immunity plays an important role in controlling herpes relapses, and
other studies have shown the efficacy of HSV-specific transfer factor (TF) for
the treatment of herpes patients, an open clinical trial was undertaken in 134
patients (71 keratitis, 29 kerato-uveitis, 34 uveitis) suffering from recurrent
ocular herpetic infections. The mean duration of the treatment was 358 days, and
the entire follow-up period 189,121 before, and 64,062 days after TF treatment.
The cell-mediated immune response to the viral antigens, evaluated by the
lymphocyte stimulation test (LST) and the leucocyte migration test (LMT) (P <
0.001), was significantly increased by the TF treatment. The total number of
relapses was decreased significantly during/after TF treatment, dropping from
832 before, to 89 after treatment, whereas the cumulative relapse index (RI)
dropped, during the same period, from 13.2 to 4.17 (P < 0.0001). No side
effects were observed. It is concluded that patients with relapsing ocular
herpes can benefit from treatment with HSV-specific TF.
observations using HIV-specific transfer factor in AIDS.
Pizza G, Chiodo F, Colangeli V, Gritti F, Raise E, Fudenberg HH, De Vinci
C, Viza D.
Immunodiagnosis and Immunotherapy Unit, Ospedale S. Orsola-Malpighi, Bologna,
Twenty five HIV-1-infected patients, at various stages (CDC II, III and IV)
were treated orally with HIV-1-specific transfer factor (TF) for periods varying
from 60 to 1870 days. All patients were receiving antiviral treatments in
association with TF. The number of lymphocytes, CD4 and CD8 subsets were
followed and showed no statistically significant variations. In 11/25 patients
the number of lymphocytes increased, whilst in 11/25 decreased; similarly an
increase of the CD4 lymphocytes was observed in 11/25 patients and of the CD8
lymphocytes in 15/25. Clinical improvement or a stabilized clinical condition
was noticed in 20/25 patients, whilst a deterioration was seen in 5/25. In 12/14
anergic patients, daily TF administration restored delayed type hypersensitivity
to recall antigens within 60 days. These preliminary observations suggest that
oral HIV-specific TF administration, in association with antiviral drugs, is
well tolerated and seems beneficial to AIDS patients, thus warranting further
Clinical trial, phase i
Anticancer Res 1990 Sep-Oct;10(5A):1183-7
transfer factor with activity against Epstein-Barr virus reduces late
relapse in endemic Burkitt's lymphoma.
Neequaye J, Viza D, Pizza G, Levine PH, De Vinci C, Ablashi DV, Biggar RJ,
University of Ghana School of Medicine, Accra.
Twenty-seven children with abdominal Burkitt's lymphoma (stage III), who had
achieved complete remission, were entered into a prospective controlled trial of
adjunct treatment with Epstein-Barr virus (EBV)-specific transfer factor (TF).
Two patients treated with TF and 2 controls relapsed early (less than or equal
to 12 weeks). Two out of 12 TF-treated patients and 5 out of 11 controls
subsequently suffered relapses. Time to first late relapse was longer among
TF-treated patients (p = 0.08), and no late relapse occurred while a patient was
receiving TF treatment. Thus it seems that specific TF might be useful in the
management of endemic Burkitt's lymphoma and also in the treatment of other
virus-associated cancers and diseases.
Controlled clinical trial
factor and repeated otitis media.
Cell Immunol 1984 Nov;89(1):259-64
Kaminkova J, Lange CF.
The effect of transfer factor (TF) was investigated in 12 children with
repeated otitis media. These patients were immunologically compared to a control
group of 23 age-matched healthy children. Levels of immunoglobulins, total and
"active" T-cells, and phagocytic activity of granulocytes and
monocytes were evaluated in the 12 children prior to, during, and after TF
therapy. Percentages of "active" T cells and absolute numbers of
"active" T and total T cells, which were initially low in the patient
group, increased significantly after TF therapy to statistically match those of
the healthy control group. The percentage of phagocytic monocytes in patients
after therapy did not differ from healthy children; however, the percentage of
phagocytic granulocytes remained depressed significantly. The levels of IgG, IgA,
and IgM were unaffected by the therapy although the IgA and IgM were higher in
the patient population throughout the study. After therapy, one-half of the
patient population remained asymptomatic for a 1-year period and the others had
markedly reduced attack rates.
of childhood combined Epstein-Barr virus/cytomegalovirus infection with
oral bovine transfer factor.
Lancet 1981 Jul 18;2(8238):122-4
Jones JF, Minnich LL, Jeter WS, Pritchett RF, Fulginiti VA, Wedgwood RJ.
An illness lasting for two years, with recurrent fever, rash, abdominal pain,
and arthralgia, developed in a four year old boy. He was found to have a
combined Epstein-Barr virus and cytomegalovirus (CMV) infection. His symptoms,
CMV in his urine, and an absent in vitro lymphocyte response to CMV antigen
persisted for two years. After treatment with orally administered bovine
transfer factor clinical symptoms and viruria disappeared and specific immunity
to CMV developed. Evaluation of this treatment in chronic virus infections is
'transfer factor': an oligoribonucleopeptide which initiates
antigen-specific lymphocytes responsiveness.
Wilson GB, Paddock GV, Fudenberg HH.
Bovine transfer factor (TF)--active in initiating specific responsiveness in
human thymus-derived (T) lymphocytes to purified protein derivative from
Mycobacterium tuberculosis (PPD) in vitro--was partially purified from the
dialyzable portion of medium from immune lymph node cells (DLNE). Its
physiochemical properties and structure were determined by methods previously
employed to characterize human PPD-specific TF isolated from dialyzable
leukocyte extracts (DLE). Bovine TF had a molecular weight (MW) of 1100-3000,
was destroyed by heating at 56 or 80 degrees C for 30 min, was soluble in water
but not in phenol or ether, and could be precipitated with ethanol. Bovine TF
activity eluted as a single peak after high-pressure reverse-phase liquid
chromatography (HPLC); the active moiety contained at least one free co-planar
cis-diol group, as shown by boronate affinity chromatography. Additional
structural features were deduced by evaluating TF activity after incubation with
various endonucleases, exonucleases, and peptidases, a phosphatase, and a
protease. The combined results indicate that bovine TF specific for PPD is an
oligoribonucleopeptide. A simplest case molecular model was constructed on the
basis of the data obtained. A comparative evaluation of the physicochemical
properties and structural features of bovine TF and human TF specific for PPD
indicated striking similarities and some differences
response modifiers. Interferons, interleukins, and transfer factor.
Ann Allergy 1989 Mar;62(3):170-6
Department of Medicine, National Jewish Center for Immunology and Respiratory
Medicine, Denver, Colorado.
Natural consequences of knowledge of the mechanisms that regulate immune
responses are the attempts to modify the immune system in order to increase
resistance to infectious diseases and to enhance activity against tumor cells.
This review describes the roles of interferons and interleukins in immune
responses and reviews the experience with transfer factor in treatment of
nature and functions of transfer factors.
Ann N Y Acad Sci 1993 Jun 23;685:362-8
Conrad D. Stephenson Laboratory for Research in Immunology, National Jewish
Center for Immunology and Respiratory Medicine, Denver, Colorado 80206.
Transfer factors are molecules that "educate" recipients to express
cell-mediated immunity. This effect is antigen-specific. The most consistent
effects of transfer factors on the immune system are expression of delayed-type
hypersensitivity and production of lymphokines such as macrophage migration
inhibitory factor (MIF), which is probably identical to gamma-interferon in
response to exposure to antigen. Transfer factors bind to antigens in an
immunologically specific manner. This discovery has enabled us to isolate
individual transfer factors from mixtures that contain several transfer factors.
This reactivity probably explains the specificity of individual transfer
factors, and it has provided a method for purification of individual transfer
factors to apparent homogeneity. The purified materials are immunologically
active and antigen-specific. They have molecular weights of approximately 5,000
Da and appear to be composed entirely of amino acids. Transfer factors appear to
offer a novel means of molecular immunotherapy for certain patients with
defective cell-mediated immunity.