Transfer Factor as an Option for Managing the COVID-19 Pandemic.

Covid-19 or SARS-CoV-2, a new RNA virus with high infectivity, and seemingly low mutability, which appeared in 2019 in the Wuhan province of China, has created a pandemic with dire consequences. At the end of May 2020, it became the first cause of mortality. As no treatment or vaccine may become available before many months, and because occurrence of similar pandemics is only a matter of time, arguments are presented here for testing the effect of transfer factor (TF), an immunomodulator devoid of toxicity, which has been extensively studied in the past for the treatment and prevention of viral infections.

Transfer factor: an overlooked potential for the prevention and treatment of infectious diseases.

Transfer factor (TF) is a low-molecular-weight lymphocyte extract capable of transferring antigen-specific cell-mediated immunity (CMI) to T lymphocytes. It has been used successfully as an adjuvant or primary therapy for viral, parasitic, fungal, and some bacterial infections, as well as immunodeficiencies, neoplasias, allergies and autoimmune diseases. From the list of infections that seem to respond noticeably to transfer factor, those due to viruses of the herpes family are particularly remarkable. Indeed, for these viruses it was shown that TF can prevent infection or relapse, acting as a CMI vaccine. Data also suggest its possible use for adjuvant treatment and probably prevention of two currently widespread infections: tuberculosis and AIDS. Furthermore, TF has an interesting potential: answering the challenge from unknown pathogenic agents, a black box effect permitting production of antigen-specific TF to a new pathogen, even before its identification. It thus seems that the preventative potential of transfer factor is as important as its therapeutic one, both discussed in this review.

Human immunodeficiency virus type 1 productive infection in staurosporine-blocked quiescent cells.

Staurosporine, an antibiotic known to inhibit cellular protein kinases, can reversibly block the progress of normal and tumour cells into the cell cycle. The ability of HIV-1 to infect and replicate in cells blocked by staurosporine was investigated. The results show that blocked, non-cycling cells can be productively infected by HIV-1, steadily releasing infectious progeny virus for several weeks. This suggests that at least in some cases, HIV-1 can be found in a stable and active state in resting, non-proliferating T cells.

HHV-6 inhibition by two polar compounds.

Dimethyl sulphoxide and dimethyl formamide, two polar compounds and powerful cell differentiation inducers, inhibit HHV-6 infection when added to HHV-6-infected HSB2 cultures. This was established by a delay in the time-course of infection and in the development of virus-induced cytopathic effects. Furthermore, viral titration of supernatants showed a significant reduction (3 log10) of the number of infectious particles. Electron microscopy confirmed that viable cells and extracellular virions were present in the cultures containing the polar compounds, while in the non-treated cultures all cells were lysed and no extracellular virus was evident. The mode of action of these compounds is still unclear and warrants further investigation.

Chemical inactivation of human immunodeficiency virus in vitro.

Most chemicals with potential virucidal activity are extremely cytotoxic even at very small concentrations, thus introducing a number of technical problems and uncertainties in the evaluation of the net virucidal effect. In the present study, an attempt was made to confirm the reported virucidal activity of certain well-known chemicals and a number of new compounds were investigated. The results suggest that HIV inactivation is dependent on the viral concentration, the time of incubation in presence of the putative disinfectant and the degree of virucidal activity of the latter. The data illustrate methodological problems arising from residual cytotoxicity of the chemical which may mask or mimic the presence of a true virucidal activity and lead to erroneous conclusions. Alcohol, the most commonly used disinfectant, was found to be ineffective for high viral concentrations, whilst sodium hypochlorite was the most efficient.

Soluble extracts from a lymphoblastoid cell line modulate simian immunodeficiency syndrome (SAIDS) evolution.

Nineteen Macaca fascicularis monkeys were injected with SIV. They were subsequently divided into 5 groups. Four groups of 4 animals were injected with dialysable extracts (DLE) from a lymphoblastoid cell line which had been previously induced with DLE obtained either from the total lymphocyte population, or from the CD4 or CD8 subpopulations of mice immunized with SIV virus. The other three animals which constituted the control group received saline injections. The animals were kept under observation for a 108-day period, and the values of several biological parameters were compared in a multivariant statistical analysis. On the 108th day, the control group was significantly different from the other groups in the multivariant analysis. Furthermore, the CD4/CD8 ratio and the platelets and CD4 cell counts varied significantly between the groups in the univariant analysis. It is thus surmised that DLE obtained from CD8 cells or the total lymphocyte population of immunized animals may exert a modulating effect on the evolution of SAIDS.

Specific transfer factor with activity against Epstein-Barr virus reduces late relapse in endemic Burkitt's lymphoma.

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.

[Treatment of herpes infections with transfer factor]. / Traitement des infections herpétiques par le facteur de transfert.

Twelve patients suffering from recurrent herpetic infections resistant to several current therapies were treated for a 3 to 10 months period with a bovine transfer factor specific to Herpes simplex virus of type 1 and 2. The results obtained showed that this treatment was capable of dramatically reducing the intensity, duration and frequency of the relapses. This preliminary clinical trial suggests that specific transfer factor administered orally could be an effective treatment of herpes infections.

AIDS and transfer factor: myths, certainties and realities.

At the end of the 20th century, the triumph of biology is as indisputable as that of physics was at the end of the 19th century, and so is the might of the inductive thought. Virtually all diseases have been seemingly conquered and HIV, the cause of AIDS, has been fully described ten years after the onset of the epidemic. However, the triumph of biological science is far from being complete. The toll of several diseases, such as cancer, continues to rise and the pathogenesis of AIDS remains elusive. In the realm of inductive science, the dominant paradigm can seldom be challenged in a frontal attack, especially when it is apparently successful, and only what Kuhn calls "scientific revolutions" can overthrow it. Thus, it is hardly surprising that the concept of transfer factor is considered with contempt, and the existence of the moiety improbable: over forty years after the introduction of the concept, not only its molecular structure remains unknown, but also its putative mode of action contravenes dogmas of both immunology and molecular biology. And when facts challenge established dogmas, be in religion, philosophy or science, they must be suppressed. Thus, results of heterodox research become henceforth nisi-i.e., valid unless cause is shown for rescinding them, because they challenge the prevalent paradigm. However, when observations pertain to lethal disorders, their suppression in the name of dogmas may become criminal. Because of the failure of medical science to manage the AIDS pandemic, transfer factor, which has been successfully used for treating or preventing viral infections, may today overcome a priori prejudice and rejection more swiftly. In science, as in life, certainties always end up by dying, and Copernicus' vision by replacing that of Ptolemy.

Identification of an antigen associated with malignant melanoma.

Xeno-antisera, prepared by immunization with soluble membrane material obtained from melanoma tumours and partially purified by column chromatography, were found to detect an antigenic specificity common to some tumour extracts and sera of melanoma patients. The presence of this antigen in patients' sera allows speculation for its possible use for early diagnosis of metastases and its role in the blocking of the immunological defences of the melanoma patients. Preparation of monospecific antisera by immunization with insoluble serum-antigen/antibody complexes has been successfully undertaken.

In vitro production of a transfer factor specific for transitional-cell carcinoma of the bladder.

Human dialysable Transfer Factor (TFd) extracted from lymphocytes of patients with transitional cell carcinoma of bladder (TCCB) was replicated in culture by lymphoblastoid cell lines. The effectiveness of two such TFdLs produced in vitro in transferring sensitivity to TCCB was assessed in the lymphocyte migration test (LMT) using formalin-treated TCCB cells as antigen. The results, showed that one TFdL transferred sensitivity in 5/14 cases and the other in 12/15, not only to leucocytes of healthy individuals but also to leucocytes of TCCB patients. Preliminary results showing an in vivo transfer of sensitivity are discussed.

Efficacy of transfer factor in treating patients with recurrent ocular herpes infections.

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.

In vitro studies during long-term oral administration of specific transfer factor.

153 patients suffering from recurrent pathologies, i.e. viral infections (keratitis, keratouveitis, genital and labial herpes) uveitis, cystitis, and candidiasis were treated with in vitro produced transfer factor (TF) specific for HSV-1/2, CMV and Candida albicans. The cell-mediated immunity of seropositive patients to HSV-1/2 and/or CMV viruses was assessed using the leucocyte migration inhibition test (LMT) and lymphocyte stimulation test (LST) in presence of the corresponding antigens, and the frequency of positive tests before, during and after TF administration was studied. The data were stratified per type of test, antigen and the recipients' pathology, and statistically evaluated. For the LMT, a total of 960 tests were carried out for each antigen dilution, 3 different antigen dilutions were used per test. 240/960 tests (25.4%) were found positive during non-treatment or treatment with unspecific TF, whereas 147/346 tests (42.5%) were found positive when the antigen corresponding to the specificity of the TF administered to the patient was used (P < 0.001). When the data were stratified following pathology, a significant increased incidence of positive tests during specific treatment was also observed (0.0001 < P < 0.05). In the LST (1174 tests), a significant increase of thymidine uptake was observed in the absence of antigen (control cultures), during treatment with both specific and unspecific TF, but also in the presence of antigen and/or autologous serum during specific TF administration (P < 0.0001). TF administration also significantly increased the soluble HLA class I antigens level in 40 patients studied to this effect.

Human lymphoblastoid cells in culture replicate immune information carried by xenogeneic RNA.

Immune RNA is obtained from lymphoid organs of immunized animals and is reputed to transfer immunological information. Human lymphoblastoid cells in culture, after incubation with sheep Immune RNA produce RNA (Ic-RNA) which carries the same immunological information as the inducing sheep preparation. This Ic-RNA produced in tissue culture is capable of converting 'naive' human lymphocytes to cytotoxic effector cells against tumour target cells, to the same extent as the Is-RNA preparation used for induction of the cell line. The sheep Immune RNA information is present and can be recovered from the lymphoblastoid cells for at least ten weeks after the induction. It is suggested that xenogeneic Immune RNA information is incorporated in a stable fashion by cultured human lymphoblastoid cells, and also that it is replicated during their own replication. This system could be used for studying the incorporation of information carried by exogenous RNA and it might provide insight into some mechanisms underlying the transfer and processing of immunological information.

Transfer factor prevents relapses in herpes keratitis patients: a pilot study.

Transfer Factor is a dialysable moiety obtained from immune lymphocytes. It has been successfully used for the treatment of several viral infections including labial and genital herpes. In the present study, thirty-three patients with low immune response to HSV antigens and suffering from herpes ocular infections were orally treated with HSV-specific transfer factor (TF). Their relapse index was reduced from 20.1 before treatment to 0.51 after TF administration, with only 6/33 patients relapsing. Although this is not a placebo-controlled-randomized study, the results suggest that TF specific for HSV antigens may be efficacious for preventing relapses of ocular herpes infections as has been the case with genital and labial localisations.