'Germs' Beat Vaccines At Their Own Game: Anti-Malarial Probiotics Show Promise

'Germs' Beat Vaccines At Their Own Game: Anti-Malarial Probiotics Show Promise

http://www.greenmedinfo.com/blog/germs-beat-vaccines-their-own-game-anti-malarial-probiotics-show-promise?page=1

Posted on: Saturday, May 30th 2015 at 9:15 am

Written By: Sayer Ji, Founder

A groundbreaking new study finds probiotic 'germs' may provide an alternative to vaccination for malaria – a finding that challenges fundamental tenets of both vaccinology and germ theory. 

The development of a malaria vaccine has been a persistent and heavily funded goal now for over half a century,[1] but to date not a single effective solution has been produced.

This is all the more surprising when you consider the roster of powerful organizations presently invested in finding one:

• Bill and Melinda Gates Foundation (particularly through PATH Malaria Vaccine Initiative)
• The US National Institute for Allergy and Infectious Disease
• The European Union DG 
• The United States Agency for International Development
• The Wellcome Trust
• The Medical Research Council UK 
• The European Vaccine Initiative (formerly EMVI)
• The European and Developing Countries Clinical Trials Partnership
• The World Health Organization [2]

Today, anti-malarial chemotherapy and so-called "vector control methods," e.g. pesticides, are the primary prevention techniques, all of which carry serious unintended adverse health effects – some at least as serious a health threat as malaria itself. Ostensibly, a malaria vaccine would reduce the need for these 'external' measures by educating the body's own immune system to fight a disease which accounts for over 207 million cases and 627,000 deaths annually, according to the World Health Organization's "World Malaria Report" (2009). [3]

The scientific justification for the development of vaccines in general and the malaria vaccine in particular is based on the observation that surviving natural exposures to pathogens often results in lasting immunity. In the case of malaria, survival from initial infection and frequent re-exposures can result in the absence of clinical symptoms of infection. Also, when gamma-globulin fractions are transferred from semi-immune to naïve humans malaria disease severity is mitigated.[4] [5]

So why, given the feasibility of a vaccine and the virtually limitless financial, scientific and technological resources available to developing an effective solution, has none yet been produced?

This question could be raised for any number of vaccines either in development or already in present day 'immunization' schedules. HIV vaccines, for instance, have been a notorious failure, even increasing death rates in a recent clinical trial. And then there are the vaccines for mostly benign childhood infections, e.g. chickenpox, measles, mumps, etc., which now require multiple 'boosters' because the synthetic immunity they produce have a dismally short if not non-existence effectiveness.  Given the growing tide of vaccine failures in highly vaccine compliant populations, including: chickenpox, shingles, measles, mumps, whooping cough (pertussis), influenza, HPV (Gardasil), hepatitis B, the problem may not lie in the virulence or resistance of a particular pathogen -- be it Ebola or malaria -- rather, the problem may lie with the fundamental tenets of vaccinology itself, including germ theory, which our discovery of the microbiome and even the viral nature of key elements of our own genome has effectively obliterated.  In other words, vaccines cannot and do not replace the type of immunity produced through natural processes and natural exposures, and surprisingly, some 'germs' are actually required to fend off infection.

The Dawn of 'Probiotic Vaccines'

Illustrating exactly this point, a recent study published in the journal Cell titled "Gut Microbiota Elicits a Protective Immune Response against Malaria Transmission," ^[6]  reveals that the human gut bacteria Escherichia coli 086:B7, normally considered a microbe of pathogenic potential within the host, may help us fend off malaria infection. This was the first study of its kind to demonstrate a beneficial effect of what is normally considered a pathogenic 'germ' on malaria infection.

Click to view the entire PDF

In the new study, Yilmaz and colleagues found that both the E. coli and malaria parasite (Plasmodium sporozites) exhibit the sugar-containing molecule glycan  Gala1-3Galb1-4GlcNAc-R (a-gal) on their surface, which is not present in humans due to the inactivation of the gene (a1,3GT ) which has been estimated to have occurred in our pre-human ancestors about 28 million years ago.[7]  This genetic deletion prevents the body from unintentionally forming autoantibodies against itself, as human are no longer capable of expressing this glycan on cell surfaces. In fact, because of this mutation the human immune system is capable of producing up to 5% of all of its circulating immunoglobulin IgM and IgG against this particular glycan.[8]

Why is this important?

Yilmaz et al observed several important phenomena that together indicate this E. coli strain (and by implication perhaps other commensal bacteria) in our gut may prime the immune system to produce anti-glycan antibodies that protect against malaria. They came to this conclusion through the following observations, summarized by a recent review of their work titled, "Coming soon: probiotics-based malaria vaccines":

• Higher anti-a-gal antibodies are correlated to lower incidence of malaria infection: "As Yilmaz et al. [7] demonstrated in their study, individuals in malaria-endemic Mali exhibit twice the levels of anti-a-gal IgM antibodies compared to adults with no previous malaria exposure. Levels were in general higher in non-infected individuals, indicating that the high titers of a-gal antibodies protect these individuals from being infected by the malaria parasite."
• Mice engineered to be deficient in the glycan-producing 1,3 GT gene (like humans) produce protective anti-a-gal antibodies following exposure to E. coli 086:B7 or vaccination with a-gal antigen: "The most interesting discovery of the authors was the demonstration that 'human-like' a1,3GT-deficient mice produce anti-a-gal antibodies following enteric exposures to E. coli O86:B7 or immunization with a-gal antigen and that these antibodies protected the mice against Plasmodium berghei infection by Anopheles stephensi mosquitoes."
• Anti-a-gal antibodies bind to the parasite surface and activate classical complement pathway of the immune system within the skin: "Yilmaz and colleagues then dissected the mode of action of the anti-a-gal antibodies during malaria transmission from the mosquito to the human. The antibodies were shown to bind to the sporozoite surface and here induced the classical pathway of complement, resulting in lysis of the sporozoites. Due to the fact that following the mosquito bite sporozoite RNA was detectable in the mouse skin, but not the liver, the initial deposition of the parasites in the skin appears to be the target for complement-mediated destruction."
• A-gal antibodies produced as a result of gut microbe exposure are able to protect against malarial infection of the skin: "[E]xisting a-gal antibodies, originally generated by the host in response to a-gal-presenting gut microbes, are able to target Plasmodium sporozoites once the mosquito injects them into the skin, resulting in complement-mediated destruction of the parasite (Figure 1)."
• While Yilmaz et al focused on the a-gal glycan as a potential vaccine target to protect against malaria infection and transmission, the review pointed out another implication: "the most innovative aspect of the study is the potential use of human gut bacteria as probiotics to protect humans from contracting malaria." The review proposed:
   "In regard to malaria prevention measures this can be achieved by the use of probiotics containing a-gal producing bacteria as dietary supplements to protect from malaria infection, particularly children who are the most vulnerable group. Antimalarial probiotics in theory would have the advantages of long-term efficacy and low production costs. However, much effort is needed to determine composition and administrative doses of such probiotics as well as the antimalarial effect and tolerance of probiotic vaccines for humans."
  Antimalarial Probiotics? 
  A probiotic vaccine? In other words, certain commensal bacteria formerly believed to be either harmless or pathogenic may induce protective antibodies in a manner that is far more effective than conventional vaccines, the latter of which cannot effectively reproduce or replace immunological processes that have taken millions of years to evolve within the metaorganism that we are (our cells + the trillions of microbes that together constitute us). In the case of malaria, this is all the more compelling, since no such vaccine has been found after six decades of investigation; a time span within which millions of people have died or been severely debilitated because of a lack of available conventional treatments.  
  Incidentally, this is not the first study to find probiotic bacteria may help fight malaria. A 2006 study titled, "Lactobacillus casei ssp. rhamnosus enhances non specific protection against Plasmodium chabaudiAS in mice", found that the  well-known probiotic strain Lactobacillus casei exhibited potent anti-malarial activity in the mouse experimental model of infection, indicating that there are a variety of bacterial strains in the gut that could be utilized to support produce probiotic-mediated immunization alternatives to vaccination.
  Moreover, considering that the hundreds of millions of dollars invested in finding drug and vaccine solutions to malaria have yet to produce compelling results, it should be noted that probiotics are not the only 'natural alternatives' that show promise. Others include:
  1.     Lime Juice: A 2011 human study found that lime juice greatly increased malarial clearance when combined with standard drug therapy. [9]They concluded: "lime juice when used with the appropriate antimalarial may enhance malaria parasite clearance especially in those with uncomplicated malaria." Lime juice, in fact, may help combat a wide range of life-threatening diseases.
  2.     Turmeric (Curcumin): There are at least 8 studies in the medical literature demonstrating the value of the primary polyphenol in turmeric known as curcumin in combatting malaria and/or reducing the adverse effects of conventional antimalarial drugs. View the studies here.
  3.     Breastmilk: Natural's original, first source of immunization is breast milk. A 2000 study found vitro growth inhibition of P. falciparum by maternal and infant sera, suggesting "a protective in vivo role for breastmilk in the possible modulation of malaria frequency, severity and complications."[10]
  For more research on natural/integrative anti-malarial interventions, take a look at our research page on the topic which includes preliminary research on over two dozen natural substances of potential value in the cause to reduce morbidity and mortality associated with malaria infection.
  
  
  References
  
  
  [1] http://rstb.royalsocietypublishing.org/content/366/1579/2806
  
  
  [2] Moran M, Guzman J, Ropars A, Jorgensen M, McDonald A, Potter S, Haile-Selassie H. The malaria product pipeline: planning for the future. London, UK: The George Institute for International Health; 2007.
  
  
  [3] World Health Organization (2013) World Malaria Report. Geneva, Switzerland. http://www.who.int/malaria/publications/world_malaria_ report_2013/wmr2013_no_profiles.pdf
  
  
  [4] Gamma-globulin and acquired immunity to human malaria. COHEN S, McGREGOR IA, CARRINGTON S Nature. 1961 Nov 25; 192():733-7. 
  
  
  [5] Antibodies that protect humans against Plasmodium falciparum blood stages do not on their own inhibit parasite growth and invasion in vitro, but act in cooperation with monocytes. Bouharoun-Tayoun H, Attanath P, Sabchareon A, Chongsuphajaisiddhi T, Druilhe PJ Exp Med. 1990 Dec 1; 172(6):1633-41.  
  
  
  [6] Yilmaz, B. et al. (2014) Gut microbiota elicits a protective immune response against malaria transmission. Cell 159, 1277–1289 8 Galili, U. and Swanson, K. (1991) Gene sequences suggest inacti
  
  
  [7] Galili, U. and Swanson, K. (1991) Gene sequences suggest inactivation of alpha-1,3-galactosyltransferase in catarrhines after the divergence of apes from monkeys. Proc. Natl. Acad. Sci. U.S.A. 88, 7401–7404
  
  
  [8] Macher, B.A. and Galili, U. (2008) The Galalpha1,3Galbeta1,4GlcNAcR (alpha-Gal) epitope: a carbohydrate of unique evolution and clinical relevance. Biochim. Biophys. Acta 1780, 75–8
  
  
  [9] S A Adegoke, O A Oyelami, O S Olatunya, L A Adeyemi. Effects of lime juice on malaria parasite clearance. Phytother Res. 2011 Oct ;25(10):1547-50. Epub 2011 Mar 17. PMID:21413089
  
  
  [10] O O Kassim, K A Ako-Anai, S E Torimiro, G P Hollowell, V C Okoye, S K Martin. Inhibitory factors in breastmilk, maternal and infant sera against in vitro growth of Plasmodium falciparum malaria parasite. J Trop Pediatr. 2000 Apr;46(2):92-6. PMID: 10822935http://www.greenmedinfo.com/blog/germs-beat-vaccines-their-own-game-anti-malarial-probiotics-show-promise?page=1