Viralox^®

Keeping Your Immune System Healthy And Performing Perfectly

by John I. Buhmeyer, MS

Without our immune system, we would live very short lives: perhaps hours or days at the most. It has been said: If you are sick, you have an immune problem. Virlually all disease is a lack or non function of immune processes. Our immune system is the most incredible defense system imaginable, yet it sometimes misfunctions, doesn't perform up to spec and leaves us withering and sick. There is a way to bring immune functions back to perfection. To restablish balance (modulation) and to quicken responses to enable us to fight infection and regain radiant health. But the key to this cannot be found in plant molecules, chemicals, or minerals. It can only be found and obtained from a healthy and properly functioning mammalian food: Colostrum, the first food of our life.

New drug-resistant bacteria, deadly new diseases like AIDS and Swine flu (H1N1 and H5N1) bird flu, herpes, hepititus, seaonal flu, viruses – the threats to our health seem everywhere. The promise of medicine triumphant against infectious disease seems now like an empty promise. If a cold virus strikes you or your family, what can you do? Over-the-counter medicines only mask the symptoms without getting at the underlying cause. Natural products derived from plants that stimulate the immune system can sometimes have dangerous side effects. Antibiotics are useless against viruses, yet doctors continue to routinely prescribe them for viral infections. What is the answer?

Medicine in the late 20th and early 21st centuries has been confronted with a disturbing dilemma – the appearance of new diseases and new strains of pathogens which defeat the best efforts of medicine to combat them. From AIDS to autoimmune diseases, new challenges keep appearing for which medicine has no good answers.

The failure of pharmaceutical responses to these challenges has been particularly unsettling. In the mid-20th century it seemed that medicine had diseases on the ropes. Vaccines had all but eliminated many ancient killers, such as smallpox and polio, and it seemed an end to all disease could only be a matter of time. The appearance of AIDS in the 1980s brought an end to this period of optimism. It appeared seemingly out of nowhere and killed nearly everyone who contracted the virus. Other pathogens appeared that had apparently discovered our Achilles heel – our immune systems – and developed ways to defeat it, such as HIV, the so-called bird flu, and the newly emerging swine flu varient H5N1, which kills by defeating the normal feedback loop that holds the immune system in balance. And the old antibiotics were not effective against resistant new bacterial strains.

Meanwhile, other diseases that were virtually unknown 100 years ago have begun to increase, slowly at first, then more rapidly. Many of these are autoimmune diseases or chemical sensitivities that indicate immune systems out of balance and unable to cope in an environment tainted with pollution and chemical toxins. The incidence of autism has dramatically increased in the last 25 years. Treatments for these exotic diseases is either lacking or ineffective, the cure often worse than the disease.

These developments have sent medical scientists back to the drawing boards to come up with new treatments. Some have stayed with the old solutions, trying to come with better vaccines and pharmaceutical drugs to counter the new threats. Others have begun to think outside the box and have sought to come up with new solutions. One particularly fruitful line of investigation has reexamined old remedies to see if the answer might have been there all along.

One natural alternative that has received a lot of attention over the past 10 years is colostrum, a baby’s first food in life, and an ancient remedy for all sorts of ills. In Ancient Egypt, colostrum was considered to be the nectar of the gods, the elixir of immortality that Horus suckled from Hathor, the Mother Cow goddess. It was widely used as a topical treatment for wound healing, for example. Other cultures have also valued colostrum throughout history as a tonic that bestows health on the young and sick. Before the invention of antibiotics, it was widely used as a treatment for infectious diseases. But then it was largely abandoned, pushed aside by the shiny newcomers.

Colostrum has proven its worth since its rediscovery as a wellness maintenance dietary supplement. Taking colostrum regularly, usually in a dried state as a capsule or powder, has been found to maintain gastrointestinal health, prevent “leaky gut” syndrome, counteract the destructive effects of NSAIDs and other drugs on the intestinal lining, heal damaged tissues rapidly, build up your stamina and strength, and perhaps most important of all, maintain a healthy, smoothly functioning immune system that is able to respond to all sorts of threats, whether it be pathogenic or chemical.

But scientists did not stop there. They have begun to look more closely at the “biologic soup” of components that make up colostrum, everything from immunoglobulins to growth factors and hormones. Colostrum is packaged by nature to provide everything the newborn, whether it be calf or human, needs to survive in its first few days of life and create a robust immune system of its own. It turns out that what works for the newborn also works for everyone else. And by a quirk of nature, bovine colostrum actually works better for humans past the newborn stage as it has a predominance of immunoglobulin G (IgG), where as humans, with their more permeable placentas, have mainly immunoglobulin A (IgA) in their colostrum. IgG is better for older humans because it provides systemic immunity rather than local immunity, which is what IgA provides.

While examining the incredibly rich composition of colostrum, scientists found several very interesting substances – a protein called Lactoferrin and small peptides called Proline-Rich Polypeptides (PRP)¹. These substances are unique in their ability to modulate the immune system, stimulating it in the case of an underactive system, such as is the case in an infection like AIDS, or suppressing it in the case of an overactive system, such as is the case in autoimmune diseases where the body makes antibody against itself². These two substances, Lactoferrin and PRP, known collectively as Lactopeptides^®, are the main ingredients of Viralox^®, a new spray product designed to keep your immune system healthy and responsive to threats.

Let’s take a look at just what these compounds do in the body.

PRP is a family of closely related peptides – short strings of amino acids, smaller than a protein – which function as molecular signaling devices³. They are found throughout the body and have different functions, but the ones derived from colostrum function mainly as immunomodulators. Lactoferrin, on the other hand, is a large protein originally discovered in milk (hence the “lacto” in the name), closely related to transferrin, a molecule which transports iron (“ferrin” refers to iron) in the body. Lactoferrin also has the ability to bind iron and other heavy metals, and it does apparently participate maintaining iron homeostasis in the body. It makes use of this ability as the principal component of the innate immune system that provides non-specific protection against a broad range of pathogens. Lactoferrin has a host of other functions as well, including anti-inflammatory and anti-tumor activity, as an analgesic, regulator of bone metabolism, reproductive functions, and embryonic development. What is important for our purposes here, though, is that both PRP and Lactoferrin act as immunomodulators, substances which fine tune the immune system, stimulating it when it is underperforming (such as during an infection), or suppressing it when it is overperforming (such as in autoimmune diseases). Thus the name “Lactopeptides”, which reflects the synergy the two compounds demonstrate when used together. In other words, both together are more effective than either separately.

Lactopeptides increase the numbers of and activity of both T and B lymphocytes⁴ and Natural Killer (NK) cells^5,6, a type of lymphocyte which hunts down and destroys pathogens and cancer cells. They also influence the maturation of undifferentiated T lymphocytes into either helper (CD4+) or suppressor T cells^7,8,9. Helper T cells activate B lymphocytes by presenting an antigen, such as a viral protein, to the B cell, which then produces antibodies to that protein¹⁰. Helper T cells also help produce memory T cells which retain the “memory” of the antigen to shorten the response time in the case of reinfection¹¹. Suppressor T cells deactivate other lymphocytes, which effectively turns off the immune response9. This is important to prevent damage to healthy tissue following an infection or other challenge.

Lymphocytes are the basic cells of the adaptive immune system, but other cell types are also important in the immune response, and Lactopeptides help control these cells as well. They are known to affect the differentiation and maturation of monocytes and macrophages, cells which scavenge the connective tissues to destroy invaders, and by doing so regulate the inflammatory process¹². As well, they are able to increase the phagocytic activity and cytotoxicity of monocytes and macrophages6. They also promote the proliferation of white blood cells, which perform a similar function in the blood as well as peripheral tissues¹³. Lactopeptides directly stimulate the production of both pro- and anti-inflammatory cytokines^6,14,15, small peptides which stimulate or suppress the immune response, another way in which they are able to modulate the immune response.

Lactopeptides are effective in a wide variety of disorders, showing potent antimicrobial activity against viruses, bacteria, fungi and protozoan parasites, as well autoimmune disorders¹⁶.

Lactopeptides and the Overactive Immune System
Immunomodulatory means that Lactopeptides can not only turn up the activity of the immune system when the body is being challenged by pathogens or toxins, but also turn down the activity when the immune system is overactive, which is the case with allergies, asthma and autoimmune disorders.

Lactopeptide has been shown to inhibit autoimmune disorders^17,17, including multiple sclerosis¹⁸ and rheumatoid arthritis¹⁹. Lactoferrin reduces the effect and duration of allergy and asthma attacks in several ways. Through its iron-binding ability, it can prevent the formation hydrogen peroxide (H2O2) and hydroxyl radicals from superoxide anion which is generated when the NADPH (nicotinamide adenine dinucleotide) in pollen grains comes into contact with mucosal surfaces of the respiratory tract²⁰. Hydrogen peroxide and hydroxyl radicals act to irritate the lining of the respiratory tract to produce airway inflammation. Lactoferrin also binds certain oligonucleotides produced by certain bacteria that also cause airway inflammation²¹.

Synergistic Actions of PRP and Lactoferrin
While similar in action in many ways, PRP and Lactoferrin also have activity which is not common to both substances but which do enhance their synergistic effect.

PRP aids in the inflammatory process by increasing the permeability of blood vessels in the skin, allowing the passage of blood cells and cytokines into the connective tissue to fight infections²².

Lactoferrin can increase the production of certain cell receptors on target cell surfaces involved in the immune response6. Since PRP function as molecular signaling devices that interact with these same cell receptors, it follows that increasing the number of receptors would increase the effect of PRP.

Antimicrobial Activity of Lactopeptide
Both Lactoferrin and PRP are potent antimicrobials in their own right. PRP, in its role as an immunomodulator and molecular signaling device, stimulates the immune system to develop immunities to pathogens, while Lactoferrin, as a protein and vital component of the innate immune system, is able to actually attack and kill pathogens using a variety of methods of attack.

Lactoferrin and PRP are two of the principal immune factors in whole colostrum. In a recent study in Italy, oral colostrum supplementation was compared to flu vaccination in the prevention of influenza. Colostrum was found to be 3 times more effective than vaccination in preventing influenza²³. It should be pointed out that subjects in the study included both healthy and high-risk cardiovascular patients, which points out the safety of colostrum and colostrum products. As Lactoferrin and PRP are much more concentrated in Viralox, it follows that Viralox may be even more effective in preventing influenza than whole colostrum.

PRP supplementation has been shown to produce immunity to viruses, including herpes viruses^24,25,26, Epstein-Barr and human herpes virus-6^26,27 (viruses implicated in chronic fatigue syndrome), HIV²⁹, measles³⁰, vesicular stomatitis virus³¹ (a close relative of the rabies virus), and others. In its immunomodulatory role, PRP may also help quell the “cytokine storm” that often proves fatal to those infected with avian (bird) flu³².

Lactoferrin interferes with viruses in a number of ways to prevent infection. One of its principal methods is to compete for binding sites with viruses on target cells. By blocking these binding sites, Lactoferrin effectively blocks infection and viral replication. It is known to block bind sites for rotavirus³³ (primary cause of diarrhea in young infants), herpes simplex virus 1 and 2³⁴, canine herpes virus³⁵, feline herpes virus³⁶, echovirus³⁷ (most common cause of aseptic meningitis in children), enterovirus³⁸ (includes polio virus and other similar viruses), human papilloma virus³⁹ (implicated in cervical and other human cancers), polio virus⁴⁰, adenovirus⁴¹ (responsible for about 10% of acute respiratory infections in children and often cause diarrhea), hanta virus⁴² (cause a deadly disease spread by rodents), respiratory syncytial virus⁴³ (most common cause of bronchiolitis and pneumonia among infants under 1 year old), and alpha (Sindbis and Semliki) viruses⁴⁴ (RNA viruses which can cause rashes, arthritis and encephalitis in humans and other animals).

Lactoferrin also binds directly to the structural proteins of certain viruses, inactivating them²⁹. It is known to do this with enterovirus 7137 (cause of severe neurologic disease, such as paralysis, meningitis and encephalitis), adenovirus^45,46, and hepatitis C virus⁴⁷. It also interferes with hemagglutination (clumping of red blood cells) by influenza viruses⁴⁸. Finally, it inhibits certain viral enzymes required for viral replication, including the reverse transcriptase enzyme of HIV-1⁴⁹ and cysteine protease⁵⁰, an enzyme common to a number of viruses and bacteria.

In addition to its actions by itself, Lactoferrin also acts synergistically with a number of important antiviral drugs, including zidovudine⁵¹ (used in the treatment of AIDS), cidofovir⁵² (an anti-cytomegalovirus drug), and acyclovir⁵³ (used in the treatment of herpes infections). The effective doses of both Lactoferrin and the antiviral drugs can be reduced significantly, which is important in terms of side effects of the drugs.

Finally, PRP as a immune modulator has proven very promising in the treatment of AIDS. Studies in Africa have shown that use of a PRP spray boosted T cells levels from well below normal to normal or near normal levels, and also remission of AIDS symptoms (such as nausea, vomiting and diarrhea) within two days of start of treatment⁵⁴. This is a very strong indication that Lactopeptide acting as an immunomodulator can restore balance to the immune system to the point where the body can fight off infections such as HIV on its own. Note that Viralox does not have specific immunity against HIV or anything else. Rather it works to help the immune system do its job much better.

Viralox comes in a spray mist form which means that it immediately is absorbed into the bloodstream when sprayed into the back of the mouth. As PRP is composed of peptides, it is readily absorbed through the gastrointestinal lining. It can even be absorbed through the skin. Other products must be absorbed through the gut, where much of the product is digested before it does any good. Only Viralox has the technology to get relief into your bloodstream rapidly, avoiding digestion in the gastrointestinal tract.

So the answer of what to do in the face of new challenges from super bugs and viruses, it is clear that Viralox provides the key. Its unique immunomodulators keep your immune system functioning at optimum levels to meet any challenge while keeping it in balance and avoiding the dangers of an underperforming or an overperforming immune system. Its safety record is unmatched by any natural or pharmaceutical product, and it is easy to use and cost effective to boot.

Disclaimer: The information presented herein is intended to provide education about topics of general interest in the nutritional and nutraceutical areas. It is not intended as medical advice. iCNR, Inc. encourages all readers to discuss questions about information contained in this article with their health care practitioners.

1. Zimecki, M, Artym, J. [Therapeutic properties of proteins and peptides from colostrum and milk] Post?py Higieny i Medycyny Doświadczalnej 59:309-323 (2005). Colostrum and milk are rich in peptides and proteins which play an active role in innate immunity. Lactoferrin has antibacterial, antifungal, antiviral, antiparasitic, and antitumor activities. It helps protect the intestinal epithelium, promotes bone growth, and accelerates the recovery of immune system function in immunocompromised animals. PRP has a variety of immunotropic functions, including the promotion of T cell maturation and inhibition of autoimmune disorders.

2. Dutta, RC. Peptide immunomodulators versus infection; an analysis. Immunology Letters. 2002; 83(3):153-61. Immune stimulators have been found to be useful in helping to fight off infections, while immunosuppressors have been found useful in autoimmune conditions and transplants.

3. Boldogh, I, Liebenthal, D, Hughes, TK, Juelich, TL, Georgiades, JA, Kruzel, ML, Stanton, GJ. Modulation of 4HNE-mediated signaling by proline-rich peptides from ovine colostrum. Journal of Molecular Neuroscience 20(2):125-134 (2003). PRP, also known as colostrinin, induces mitogenic stimulation as well as a variety of cytokines in peripheral leukocytes. It also possess antioxidant activity in pheochromocytoma (P12) cells, a cancer cell line used for in vitro studies. PRP was shown to reduce the amount of 4HNE-protein adducts, reduce intracellular levels of reactive oxygen species, inhibit 4HNE-mediated glutathione depletion, and inhibit 4HNE-induced activation of the molecular signal cascade which results in the production of c-Jun N-terminal kinase (JNK) in P12 cells. This shows that PRP acts as both an antioxidant and a molecular signaling device.

4. Julius, MH, Janusz, M, Lisowski, J. A colostral protein that induces the growth and differentiation of resting B lymphocytes. Journal of Immunology 140(5):1366-371 (1988). PRP induced resting B cells and supported their progression through the cell cycle to form mature B cells. It had the same action on splenocytes.

5. Shimizu, K, Matsuzawa, H, Okada, K, Tazume, S, Dosako, S, Kawasaki, Y, Hashimoto, K, Koga, Y. Lactoferrin-mediated protection of the host from murine cytomegalovirus infection by a T-cell-dependent augmentation of natural killer cell activity. Archives of Virology 141(10):1875-1889 (1996). Lactoferrin protected mice from cytomegalovirus infection. The mechanism of action was apparently through the stimulation of NK cell activity, as athymic nude mice showed no increase in NK cell activity and no protection against cytomegalovirus infection.

6. Artym, J. [Antitumor and chemopreventive activity of lactoferrin] Post?py Higieny i Medycyny Doświadczalnej 60:352-369 (2006). Lactoferrin participates in iron homeostasis, has immunoregulatory, anti-inflammatory, anti-tumor, and analgesic actions, regulation of bone metabolism, participates in embryonic development, reproductive functions, and others. It provides anti-tumor protection through its immunomodulatory abilities, so it is of particular value in cancer patients with impaired immunity. Lactoferrin increases the number and the activity of T and B cells and NK cells, stimulates the release of a number of cytokines (IL-1, IL-6, IL-8, IL-18, IFN-γ, TNF-α), increases the phagocytic and cytotoxic activity of monocytes and macrophages, accelerates the maturation of T and B cells, and elevates the expression of several types of cellular receptors, including CD4, zeta chain of the CD3 complex, LFA-1, CD11, ICAM-1, and selectin P. In addition, it also exhibits chemopreventive properties, regulates the activity of Phase I and Phase II enzymes which participate in the activation and detoxification of carcinogens, and regulates the composition of the intestinal flora.

7. Janusz, M, Staroscik, K, Zimecki, M, Wieczorek, Z, Lisowski, J. A proline-rich polypeptide (PRP) with immunoregulatory properties isolated from ovine colostrum. Murine thymocytes have on their surface a receptor specific for PRP. Archivum immunologiae et therapiae experimentalis (Warszava) 34(4):427-436 (1986). PRP has immunoregulatory properties. It induces the maturation of thymocytes into mature helper or suppressor T cells.

8. Wieczorek, Z, Zimecki, M, Spiegel, K, Lisowski, J, Janusz, M. Differentiation of T cells into helper cells from immature precursors: identification of a target cell for a proline-rich polypeptide (PRP). Archivum immunologiae et therapiae experimentalis (Warszava) 37(3-4):313-322 (1989). The precursors of helper T cells belong to a minor thymocyte subset bearing the Thy-1 +/-, H-2+, L3T4-, lyt 2-, CD3- phenotype. PRP induced the production of antigens consistent with mature helper T cells.

9. Zimecki, M, Staroscik, K, Janusz, M, Lisowski, J, Wieczorek, Z. The inhibitory activity of a proline-rich polypeptide (PRP) on the immune response to polyvinylpyrrolidone (PVP). Archivum immunologiae et therapiae experimentalis (Warszava) 31(6):895-903 (1983). PRP administered to a test animal before immunization with PVP inhibits the immune response to this antigen. PRP did this by increasing the activity of suppressor T cells and by increasing the generation of new suppressor T cells.

10. Bishop, GA, Haxhinasto, SA, Stunz, LL, Hostager, BS. Antigen-specific B-lymphocyte activation. Critical Reviews in Immunology 23(3):159-197 (2003). B cells have the exclusive ability to produce and secrete immunoglobulins of various types. They also function in antigen presentation and the production of a number of cytokines and chemokines.

11. Shi, M, Hao, S, Chan, T, Xiang, J. CD4+ T cells stimulate memory CD8+ T cell expansion via acquired pMHC I complexes and costimulatory molecules, and IL-2 secretion. Journal of Leukocyte Biology (2006). CD8+ memory T cell expansion following a second encounter with a pathogen is a hallmark of adaptive immunity. Antigen-specific CD4+ cells, activated by dendritic cells, stimulate the expansion of CD8+ cells.

12. Kubis, A, Marcinkowska, E, Janusz, M, Lisowski, J. Studies on the mechanism of action of a proline-rich polypeptide complex (PRP): effect on the stage of cell differentiation. Peptides 26(11):2188-2192 (2005). PRP affects the differentiation and maturation of cells of the monocyte/ macrophage lineage and may regulate in this way the inflammatory processes in which these cells participate

13. Kruzel, ML, Janusz, M, Lisowski, J, Fischleigh, RV, Georgiades, JA. Towards an understanding of biological role of colostrinin peptides. Journal of Molecular Neuroscience 17(3):379-389 (2001). PRP (colostrinin) is a potent inducer of leukocyte proliferation and of certain cytokines.

14. Alvarez-Thull, L, Kirkpatrick, CH. Profiles of cytokine production in recipients of transfer factors. Biotherapy 9(1-3):55-59 (1996). Cell cultures from mice responded to HSV infection by secreting large amounts of IL-2 and INF-γ, modest amounts of IL-10, and no IL-4. The same cells responded to concanavalin A and HSV in a similar manner, but instead of IL-2, they produced large amounts of TNF-α, showing that TF (i.e. PRP) treatment selectively affects cytokine production depending on antigenic stimulation.

15. Zablocka, A, Janusz, M, Rybka, K, Wirkus-Romanowska, I, Kupryszewski, G, Lisowski, J. Cytokine-inducing activity of a proline-rich polypeptide complex (PRP) from ovine colostrum and its active nonapeptide fragment analogs. European Cytokine Network 12(3):462-467 (2001). PRP induces the production of INF-γ, TNF-α, IL-6 and IL-10 in human whole blood cultures.

16. Zimecki, M, Artym, J. [Therapeutic properties of proteins and peptides from colostrum and milk] Post?py Higieny i Medycyny Doświadczalnej 59:309-323 (2005). Colostrum and milk are rich in peptides and proteins which play an active role in innate immunity. Lactoferrin has antibacterial, antifungal, antiviral, antiparasitic, and antitumor activities. It helps protect the intestinal epithelium, promotes bone growth, and accelerates the recovery of immune system function in immunocompromised animals. PRP has a variety of immunotropic functions, including the promotion of T cell maturation and inhibition of autoimmune disorders.

17. Dutta, RC. Peptide immunomodulators versus infection; an analysis. Immunology Letters. 83(3):153-61 (2002). Immune stimulators have been found to be useful in helping to fight off infections, while immunosuppressors have been found useful in autoimmune conditions and transplants.

18. Hughes, RA. Immunological treatment of multiple sclerosis. Journal of Neurology 230(2):73-80 (1983). Transfer factor (PRP) slowed the progession of the disease whereas interferon and levamisole did not.

19. Nitsch, A, Nitsch, FP. Clinical Use of Bovine Colostrum. Journal of Orthomolecular Medicine 13(2) (1998). Low molecular weight components of colostrum (PRPs) were used in a clinical study for the treatment of rheumatoid arthritis with promising results.

20. Kruzel, M., et al. Lactoferrin decreases pollen antigen-induced allergic airway inflammation in a murine model of asthma. Immunology 119(2):159-66 (2006). Pollen grains contain reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and in contact with mucosal surfaces generate superoxide anion (O2*-). In the presence of iron, O2*- may be converted to more reactive oxygen radicals, such as to H2O2 and/or *OH, which may augment antigen-induced airway inflammation. LF lowered the increase in cellular reactive oxygen species (ROS) levels in bronchial epithelial cells. The results suggest the utility of LF in human allergic inflammatory disorders.

21. Britigan, BE, et al. Lactoferrin binds CpG-containing oligonucleotides and inhibits their immunostimulatory effects on human B cells. Journal of Immunology 167(5):2921-28 (2001). Unmethylated CpG dinucleotide motifs in bacterial DNA, as well as oligodeoxynucleotides (ODN) containing these motifs, are potent stimuli for many host immunological responses. These CpG motifs may enhance host responses to bacterial infection and are being examined as immune activators for therapeutic applications in cancer, allergy/asthma, and infectious diseases. Lactoferrin and lactoferricin B, but not transferrin, inhibited CpG ODN stimulation of CD86 expression in the human Ramos B cell line and decreased cellular uptake of ODN, a process required for CpG bioactivity. Lactoferrin binding of CpG-containing ODN may serve to modulate and terminate host response to these potent immunostimulatory molecules at mucosal surfaces and sites of bacterial infection.

22. Janusz, M, Lisowski, J. Proline-rich polypeptide (PRP)--an immunomodulatory peptide from ovine colostrum. Archivum immunologiae et therapiae experimentalis (Warszava) 41(5-6):275-279 (1993). PRP increases the permeability of blood vessels in the skin and causes the differentiation of thymocytes into mature T cells.

23. Cesarone, MR, et al. Prevention of influenza episodes with colostrum compared with vaccination in healthy and high-risk cardiovascular subjects: the epidemiologic study in San Valentino. Clinical and Applied Thrombosis/Hemostasis 13(2):130-136 (2007). Colostrum proved to be three times more effective than vaccination in preventing influenza both in healthy subjects and high-risk cardiovascular patients, and is very cost-effective.

24. Pizza, G, Meduri, R, De Vinci, C, Scorolli, L, Viza, D. Transfer factor prevents relapses in herpes keratitis patients: a pilot study. Biotherapy 8(1):63-68 (1994). Use of HSV-specific transfer factor (PRP) reduced relapses in herpes ocular infections from 20.1 to 0.51.

25. Pizza, G, Viza, D, De Vinci, C, Palareti, A, Cuzzocrea, D, Fornarola, V, Baricordi, R. Orally administered HSV-specific transfer factor (TF) prevents genital or labial herpes relapses. Biotherapy 9(1-3):67-72 (1996). Patients with genital or labial herpes received HSV-specific transfer factor (PRP) over a course of 6 months. Controls experienced a relapse index (RI) of 61.2 while those in the experimental group had an RI of 21.4.

26. Meduri, R, et al. Efficacy of transfer factor in treating patients with recurrent ocular herpes infections. Biotherapy 9(1-3):61-66 (1996). Herpes-specific transfer factor (PRP) significantly increased the cell-mediated immune response to viral antigens in patients with recurrent ocular herpes infections, and significantly reduced relapses.

27. Ablashi, DV, Levine, PH, De Vinci, C, Whitman, JE, Jr, Pizza, G, Viza, D. Use of anti HHV-6 transfer factor for the treatment of two patients with chronic fatigue syndrome (CFS). Two case reports. Biotherapy 9(1-3):81-86 (1996). Transfer factor (PRP) specific to Human Herpes Virus-6 (HHV-6) significantly improved the clinical manifestations of one patient suffering from chronic fatigue syndrome, while another showed no improvement.

28. De Vinci, C, et al. Lessons from a pilot study of transfer factor in chronic fatigue syndrome. Biotherapy 9(1-3):87-90 (1996). Transfer factor (PRP) was used in a placebo controlled study of 20 chronic fatigue patients. Efficacy of the treatment was measured by clinical monitoring and testing for antibodies to Epstein-Barr and human herpes virus-6 antibodies. Improvement was noted in 12 of the 20 patients.

29. Raise, E, Guerra, L, Viza, D, Pizza, G, De Vinci, C, Schiattone, ML, Rocaccio, L, Cicognani, M, Gritti, F. Preliminary results in HIV-1-infected patients treated with transfer factor (TF) and zidovudine (ZDV). Biotherapy 9(1-3):49-54 (1996). HIV-1 specific transfer factor (an alternative name for PRP) plus zidovudine (ZDV) was tested for efficacy in patients with AIDS-related complex (ARC). Patients receiving both transfer factor and ZDV experienced an increase in white blood cells, CD8+ lymphocytes and IL-2 levels over those receiving ZDV alone.

30. Ferrer-Argote, VE, Romero-Cabello, R, Hernandez-Mendoza, L, Arista-Viveros, A, Rojo-Medina, J, Balseca-Olivera, F, Fierro, M, Gonzalez-Constandse, R. Successful treatment of severe complicated measles with non-specific transfer factor. In Vivo 8(4):555-557 (1994). 10 patients with severe complicated measles, a life-threatening illness, were treated with non-specific transfer factor. 8 of 9 patients experiencing respiratory failure recovered, while the single case of encephalitis was clear of neurologic sequelae within two weeks following the last dose.

31. Orzechowska, B, Janusz, M, Domaraczenko, B, Blach-Olszewska, Z. Antiviral effect of proline-rich polypeptide in murine resident peritoneal cells. Acta Virologica 42(2):75-78 (1998). It is known that resident peritoneal (RP) cells from BALB/c female mice express a constitutive non-specific antiviral immunity which is progressively reduced during several days of cultivation in vitro. In this report, we have studied the effect of a proline-rich polypeptide (PRP) isolated from ovine colostrum on the kinetics of vesicular stomatitis virus (VSV) replication in freshly isolated and one-day cultured RP cells. The polypeptide was added to the cells immediately after virus adsorption or one day before or after viral infection. Independently on time of PRP addition, an inhibition of VSV replication (virus titres reduced by up to 4 log units) was observed.

32. Chan, MC, Cheung, CY, Chui, WH, Tsao, SW, Nicholls, JM, Chan, YO, Chan, RW, Long, HT, Poon, LL, Guan, Y, Peiris, JS. Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells. Respiratory Research 6:135 (2005). H5N1 influenza viruses are potent stimulators of proinflammatory cytokines chemokines in primary human respiratory epithelial cells. This suggests that hyper-induction of cytokines may be part of the pathogenesis of the disease.

33. Superti, F, Ammendolia, MG, Valenti, P, Seganti, L. Antirotaviral activity of milk proteins: lactoferrin prevents rotavirus infection in the enterocyte-like cell line HT-29. Medical Microbiology and Immunology (Berlin) 186(2-3):83-91 (1997). Beta-lactoglobulin, apo- and iron-saturated lactoferrin inhibit rotaviral infection in a dose-dependent manner. Apo-lactoferrin prevents both rotavirus hemagglutination and viral binding to susceptible cells. It also markedly inhibits rotavirus antigen synthesis when added during the virus adsorption step.

34. Jenssen, H. Anti-herpes simplex virus activity of lactoferrin/lactoferricin – an example of antiviral activity of antimicrobial protein/peptide. Cellular and Molecular Life Sciences 62(24):3002-3013 (2005). Lactoferrin and a peptide derived from lactoferrin, lactoferricin, block entry of HSV into cells.

35. Tanaka, T, Nakatani, S, Xuan, X, Kumura, H, Igarashi, I, Shimazaki, K. Antiviral activity of lactoferrin against canine herpes virus. Antiviral Research 60(3):193-199 (2003). Bovine lactoferrin inhibits both the infection and replication of canine herpes virus in vitro.
36. Beaumont, SL, Maggs, DJ, Clarke, HE. Effects of bovine lactoferrin on in vitro replication of feline herpes virus. Veterinary Ophthalmology 6(3):245-250 (2003). Bovine lactoferrin has a notable inhibitory effect on the in vitro replication of feline herpes virus prior to and during viral adsorption, but not after. It appears that the lactoferrin blocks adsorption to the cell surface and/or penetration of the virus into the cell.

37. Pietrantoni, A, Ammendolia, MG, Tinari, A, Siciliano, R, Valenti, P, Superti, F. Bovine lactoferrin peptidic fragments involved in inhibition of Echovirus 6 in vitro infection. Antiviral Research 69(2):98-106 (2006). Lactoferrin inhibits Echovirus 6 infection by blocking viral attachment to cell receptors, possibly due to the cluster of positive charges at its N-terminus.

38. Weng, TY, Chen, LC, Shyu, HW, Chen, SH, Wang, JR, Yu, CK, Lei, HY, Yeh, TM. Lactoferrin inhibits enterovirus 71 infection by binding to VP1 protein and host cells. Antiviral Research 67(1):31-37 (2005). Lactoferrin binds to host cells, preventing enterovirus 71 from attaching to them. It also interferes with the virus by binding to its VP1 protein.

39. Drobni, P, Naslund, J, Evander, M. Lactoferrin inhibits human papilloma virus binding and uptake in vitro. Antiviral Research 64(1):63-68 (2004). Lactoferrin, particularly bovine lactoferrin, blocks entry of human papilloma virus (HPV) into target cells in vitro. HPV has been implicated in the development of cervical and other cancers.

40 McCann, KB, Lee, A, Wan, J, Roginski, H, Coventry, MJ. The effect of bovine lactoferrin and lactoferricin B on the ability of feline calicivirus (a norovirus surrogate) and poliovirus to infect cell cultures. Journal of Applied Microbiology 95(5):1026-1033 (2003). Lactoferrin interfered with the infection of cells by both feline calicivirus and poliovirus.

41 Arnold, D, Di Biase, AM, Marchetti, M, Pietrantoni, A, Valenti, P, Seganti, L, Superti, F. Antiadenovirus activity of milk proteins: lactoferrin prevents viral infection. Antiviral Research 53(2):153-158 (2002). Lactoferrin prevented viral infection by adenovirus when added before or during the viral adsorption stage.

42. Murphy, ME, Kariwa, H, Mizutani, T, Tanabe, H, Yoshimatsu, K, Arikawa, J, Takashima, I. Characterization of in vitro and in vivo antiviral activity of lactoferrin and ribavirin upon hanta virus. Journal of Veterinary Medicine and Science 63(6):637-645 (2001). Lactoferrin alone or ribavirin alone significantly inhibited hantavirus focus formation in vitro. When combined, the two completely inhibited focus formation. Lactoferrin inhibits adsorption of the virus to cells, and ribavirin inhibits viral protein synthesis.

43. van der Strate, BW, Beljaars, L, Molema, G, Harmsen, MC, Meijer, DK. Antiviral activities of lactoferrin. Antiviral Research 52(3):225-239 (2001). Lactoferrin has antiviral activity against both DNA and RNA viruses, including respiratory syncytial virus, herpes virus, rotavirus and HIV. Its mechanism of action is mainly to block entry of the virus into target cells, either by blocking receptors on target cells or directly binding to virus particles.

44. Waarts, BL, Aneke, OJ, Smit, JM, Kimata, K, Bittman, R, Meijer, DK, Wilschut, J. Antiviral activity of human lactoferrin: inhibition of alpha virus interaction with heparan sulfate. Virology 333(2):284-292 (2005). Lactoferrin inhibits viral infection by alphaviruses (Sindbis and Semliki Forest) by interfering with virus-receptor interaction.

45. Pietrantoni, A, Di Biase, AM, Tinari, A, Marchetti, M, Valenti, P, Seganti, L, Superti, F. Bovine lactoferrin inhibits adenovirus infection by interacting with viral structural polypeptides. Antimicrobial Agents and Chemotherapy 47(8):2688-91 (2003). In addition to competeing for common receptors on target cells, lactoferrin also neutralizes infection by adenovirus by binding to adenovirus particles, specifically viral III and IIIa polypeptides.

46. Seganti, L, Di Biase, AM, Marchetti, M, Pietrantoni, A, Tinari, A, Superti, F. Antiviral activity of lactoferrin towards naked viruses. Biometals 17(3):295-299 (2004). Lactoferrin is a well-known potent inhibitor of naked viruses, including rotavirus, enterovirus, and adenovirus. Lactoferrin is especially potent against viruses which replicate in the gastrointestinal system as it is resistant to tryptic digestion. Against rotavirus, it prevents viral attachment to the gastrointestinal wall by binding to viral particles, and it inhibits a post adsorption step. Lactoferrin interferes with an early infection step of the polio virus, and iron-saturated lactoferrin inhibits viral replication after the adsorption phase.

4.7 Nozaki, A, Ikeda, M, Naganuma, A, Nakamura, T, Inudoh, M, Tanaka, K, Kato, N. Identification of a lactoferrin-derived peptide possessing binding activity to hepatitis C virus E2 envelope protein. Journal of Biological Chemistry 278(12):10162-10173 (2003). Both human and bovine lactoferrin prevent hepatitis C infection in vitro. A peptide in the lactoferrin molecule has been shown to a viral envelope protein, by which it apparently blocks the viral particles from binding to target cells.

48. Kawasaki, Y, Isoda, H, Shinmoto, H, Tanimoto, M, Dosako, S, Idota, T, Nakajima, I. Inhibition by kappa-casein glycomacropeptide and lactoferrin of influenza virus hemagglutination. Bioscience, Biotechnology, and Biochemistry 57(7):1214-1215 (1993). Lactoferrin inhibits the hemagglutination (clumping of blood cells) of the influenza virus. Hemagglutination inhibition is one of the tests which show the effectiveness of influenza vaccines.

49. Ng, TB, Lam, TL, Au, TK, Ye, XY, Wan, CC. Inhibition of human immunodeficiency virus type 1 reverse transcriptase, protease and integrase by bovine milk proteins. Life Science 69(19):2217-11^22,23 (2001). Lactoferrin strongly inhibits HIV-1 reverse transcriptase and slightly inhibited HIV-1 protease and integrase, enzymes which are crucial to the HIV-1 life cycle.

50. Ohashi, A, Murata, E, Yamamoto, K, Majima, E, Sano, E, Le, QT, Katunuma, N. New functions of lactoferrin and beta-casein in mammalian milk as cysteine protease inhibitors. Biochemistry and Biophysics Research Communications 306(1):98-103 (2003). Lactoferrin inhibits cathepsin L (a cysteine protease inhibitor), an activity which is dependent on the tertiary structure of lactoferrin. A peptide of lactoferrin shows 90% homology with the sequences of a common active site of cystatins.

51. Viani, RM, Gutteberg, TJ, Lathey, JL, Spector, SA. Lactoferrin inhibits HIV-1 replication in vitro and exhibits synergy when combined with zidovudine. AIDS 13(10):1273-1274 (1999). Lactoferrin in combination with zidovudine is more effective than either alone in inhibiting HIV-1 replication.

52. van der Strate, BW, De Boer, FM, Bakker, HI, Meijer, DK, Molema, G, Harmsen, MC. Synergy of bovine lactoferrin with the anti-cytomegalovirus drug cidofovir in vitro. Antiviral Research 58(2):159-165 (2003). Combining lactoferrin with acyclovir or foscarnet resulted in antagonism, lactoferrin and ganciclovir showed neither antagonism or synergy, but lactoferrin with cidofovir showed marked synergy against cytomegalovirus.

53. Andersen, JH, Jenssen, H, Gutteberg, TJ. Lactoferrin and lactoferricin inhibit Herpes simplex 1 and 2 infection and exhibit synergy when combined with acyclovir. Antiviral Research 58(3):209-215 (2003). When used against HSV-1 and -2, the combination of lactoferrin or its peptide lactoferricin with acyclovir demonstrated good synergy. The effective dosage of both lactoferrin and acyclovir could be reduced 2-7 times.

54. Keech, A. (2006) Unpublished data.