The Crossroads of Immunology and Homeopathy. Tetyana Obukhanych, PhD HP Worldwide Choice Conference, 2016

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1 The Crossroads of Immunology and Homeopathy Tetyana Obukhanych, PhD HP Worldwide Choice Conference,

2 Conventional View of Immunity Immune system => resolution of infection Immunity = protection from (re)infection The immune system Adaptive branch Innate branch Passive (serum transfer) vaccination Innate Immunity Acquired Immunity 2

3 Traditional View of Acquired Immunity The basis of acquired immunity from viral re-infection is traditionally believed to be immunologic memory, seated in the adaptive branch of the immune system. antigen Auxiliary help Cellular component: naïve vs. memory B lymphocytes (B cells) Humoral component (in bodily fluids): antibodies Is traditional view of acquired immunity correct? 3

4 Experimental Demonstration: Immunologic Memory Clinical Protection Infected with VSV All died mice with compromised innate immune system healthy mice infected with VSV mice with compromised innate immune system Infected with VSV Protected VSV = vesicular stomatitis virus Steinhoff et al. (1995) J Virol 69:

5 Dr. Rolf Zinkernagel 5

6 Further Evidence That Immunologic Memory Does Not Protect from Infection or Disease Despite pre-existing measles-specific memory lymphocytes, in the absence of protective serum titers macaques developed measles upon exposure. Lin et al. (2014) Mbio 5:e01047 Measles in vaccinated persons despite evidence of re-activation of immunologic memory. Rosen et al. (2014) Clin Infect Dis 58:

7 Is It Antibody? Humoral immunity is believed to be antibody-based antigen Auxiliary help THIS BELIEF PERSISTS DESPITE CLINICAL OBSERVATIONS TO THE CONTRARY 7

8 Development of Immunity in the Apparent Absence of Antibodies To everyone s surprise [children with agammaglobulinemia] showed a normal measles course with a typical rash which faded at the normal time and was followed by just as substantial immunity against reinfection as would be shown by any other convalescent. Antibody production is therefore not necessary either for recovery from or for the development of immunity to measles. -Sir MacFarlane Burnet Natural History of Infectious Disease, p Sir MacFarlane Burnet

9 Lack of Immunity Despite the Presence of Virus-Specific Antibodies Hospital employees working in patient care areas from July through November 1990 were screened for measles antibody levels using a commercially available enzyme immunoassay (EIA). Four healthcare workers vaccinated in the past developed measles. All had positive pre-illness measles antibody levels. Ammari et al. (1993) Infect Control Hosp Epidemiol 14:

10 Protective Serum Titers vs. Antibody Titers Protective serum titers are determined by: Purifying a serum sample; Serially-diluting (titrating) the sample; Incubating each serial dilution with a live virus; Determining the highest serial dilution that destroys infectivity of the live virus. Antibody titer tests (e.g. ELISA, EIA) measure the levels of virus-specific antibodies based on binding properties of antibodies to their antigens. 10

11 Wild VSV Inactivated VSV Protective Serum Titers for VSV Antibodies to VSV (ELISA test) 11 VSV = vesicular stomatitis virus Ochsenbein et al. (2000) Proc Natl Acad Sci USA 97:

12 The Paradox of Immunity Protective immunity is NOT based on immunologic memory (quicker and better secondary response of memory lymphocytes to previously encountered viruses). Protective immunity is humoral in nature and can be transferred for a short-term (e.g. maternal immunity transfer, immune serum transfer). Although humoral immunity is believed to be antibody-based, antibodies are neither necessary nor sufficient to confer immunity. Protective serum titer tests do not measure antibodies per se they measure protective activity. It remains a possibility that what is being measured is yet an unknown carrier of immunity. Immunology has stopped its quest for the basis of immunity without acknowledging and resolving the existing paradox. 12

13 Good Ol Vaccine Paradigm virus VACCINOLOGY (ATTENUATED OR DEAD FORM) VACCINATION Natural exposure Disease resolution LIFE-LONG IMMUNITY Vaccination was believed to be educating the immune system with a dead/attenuated form of a pathogen, so that it would be recognized faster when met naturally. Vaccination was equated to contracting a weak or dead form of disease, only with less or no risk, compared to contracting a disease. Vaccination was believed to give life-long immunity from infection. 13

14 A Shot at Measles The availability of potent and effective measles vaccines provides the basis for the eradication of measles in any community that will raise its immune thresholds to readily attainable levels. Effective use of these vaccines during the coming winter and spring should ensure the eradication of measles from the United States in Sencer et al. (1967) Public Health Reports 83:

15 Endemic Measles in the U.S. Was Declared Eliminated Decades Later than Expected 1963 Endemic measles eradication started 2000 Endemic measles declared eliminated in the U.S. 15

16 The Measles Paradox The apparent paradox is that as measles immunization rates rise to high levels in a population, measles becomes a disease of immunized persons. Poland & Jacobson (1994) Arch Intern Med 154: Gregory Poland, MD 16

17 Measles in Highly Vaccinated Schools Year of publication % of school vaccinated 1977 > % of cases vaccinated Not Reported Year of publication % of school vaccinated Not Reported % of cases vaccinated Because of the failure rate of the vaccine and the unique transmissibility of the measles virus, the currently available measles vaccine, used in a single-dose strategy, is unlikely to completely eliminate measles. The long-term success of a two-dose strategy to eliminate measles remains to be determined. Poland & Jacobson (1994) Arch Intern Med 154:

18 Measles Eradication Prognosis: 1994 vs The apparent paradox is that as measles immunization rates rise to high levels in a population, measles becomes a disease of immunized persons. Because of the failure rate of the vaccine and the unique transmissibility of the measles virus, the currently available measles vaccine, used in a single-dose strategy, is unlikely to completely eliminate measles. The long-term success of a two-dose strategy to eliminate measles remains to be determined. To date, despite multiple efforts, the reality is that for the practical, sociocultural, and immunologic reasons we have not eradicated measles. As a result, measles is re-emerging as a public health threat, and our current tool for prevention has limitations that increasingly look to be significant enough that sustained elimination, much less eradication, is unlikely. Perhaps it is time to consider, in earnest, the development of the next generation of measles vaccines. Poland & Jacobson (2012) Vaccine 30: Poland & Jacobson (1994) Arch Intern Med 154:

19 Outbreak of Measles in Fraser Valley, British Columbia, 2014 (religious non-vaccinating community) Public Health Agency of Canada A total of 433 cases (325 confirmed and 108 probable) were identified. Rash onset ranged from February 22 to June 9, with 98% during March and April. Fifty-seven percent of cases were students of one school. The median age of cases was 11 years and 68% of cases were aged five to 19 years. Ninety-nine percent of cases were unvaccinated. 19

20 Outbreak of Measles in a Vaccine-Compliant Quebec Community, 2011 The affected community had 95-97% measles vaccination coverage and no concentrated pockets of unvaccinated groups. Imported by a high-school teacher, himself vaccinated for measles in his childhood. This single importation affected 678+ people, starting with high-school students. The overall contribution of twice-vaccinated individuals constituted 48% of measles cases (significantly underreported in the official Canadian statistics, but pointed out by researchers who performed active surveillance of measles cases). De Serres et al. (2013) J Infect Dis 207:

21 Protective Measles Titers in Vaccinated vs. Naturally Immune People Comparative analysis of titers against measles virus in sera of vaccinated and naturally infected Japanese individuals of different age groups. Key findings: The vaccinated group was (~ 9-fold) lower in virus-neutralizing serum titers for measles compared to the group that had natural measles infection in the past. Naturally immune elderly (>60 years old) had high virus-neutralizing titers. Itoh et al. (2002) J Clin Microbiol 40:

22 Waning of Protective Measles Titers after Second MMR shot LeBaron et al. (2007) Arch Pediatr Adolesc Med 161:

23 Vaccination Reality virus VACCINOLOGY Attenuated or dead form of the virus VACCINATION Natural infection Quest to fully understand immunity and its practical applications must continue. Temporary protection LIFE-LONG IMMUNITY 23

24 Rediscovering HP virus VACCINOLOGY HOMEOPROPHYLAXIS MATERIAL COMPONENT (ATTENUATED OR DEAD FORM) Natural infection ENERGETIC COMPONENT VACCINE Disease-specific HP remedy Temporary protection LIFE-LONG IMMUNITY Preventing natural infection or Giving energetic disease? 24

25 Considerations about HP Use HP use during an outbreak versus as a routine childhood application. Analysis of adverse reactions after routine HP application for individual cases. HP is NOT a replacement for the foundation of a healthy immune system, which is built with daily health-supporting measures, such as nutrition, breastfeeding of infants, detoxification, supporting gut microbiome, etc. 25

26 Childhood Infections Lower the Risk of Atopy Measles lowers the risk of atopy, hay fever & asthma Shaheen et al. (1996) Lancet 347: Rosenlund et al. (2009) Pediatrics 123: Chickenpox lowers the risk of hay fever, asthma & atopic dermatitis Children who had wild varicella infection (compared to those who had varicella vaccination) exhibited lower levels of IgE antibodies and lower counts of peripheral blood lymphocytes, and basophils (a type of granulocyte associated with anaphylaxis) for many years to come. Silverberg et al. (2012) Pediatrics 23:

27 Childhood Infections Lower the Risk of Lymphomas The history of childhood infections (measles, mumps, rubella, chickenpox) are associated with a lower risk of Hodgkin s lymphoma; measles is associated with a lower risk of non-hodgkin s lymphoma. Alexander et al. (2000) Br J Cancer 82: Glaser et al. (2005) Int J Cancer 115: Montella et al. (2006) Leuk Res 30:

28 Mumps Primes the Immune System Against Ovarian Cancer The history of mumps is associated with a lower risk of ovarian cancer: When parotid glands are infected with the mumps virus, they swell and produce a new antigen called MUC-1 Thus, mumps infection primes the immune system against MUC-1 Ovarian cancer also produces MUC-1 antigen Cramer et al. (2010) Cancer Causes Control 21:

29 Chickenpox Lowers the Risk of Glioma To date, VZV [varicella zoster virus] is the only virus consistently reported to have an inverse association with glioma. We found that a positive history of chickenpox was associated with a 21% lower glioma risk. Furthermore, the protective effect of chickenpox was stronger for high-grade gliomas. A particularly interesting finding of our study is that the protective effect of chickenpox against high grade glioma was strongest among the youngest (<40) age group [a 47% lower glioma risk]. Median age at glioma development is 55 years. It is possible that high grade gliomas that develop in younger individuals are etiologically heterogeneous from those that develop in older individuals. Amirian et al. (2016) Cancer Med 5: