Compiled by Liora  Pearlman

VACCINES AND THE DS IMMUNE SYSTEM

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Contents;
SECTION 1 Medical studies that argue AGAINST vaccinating kids with DS (12 studies found). Low seroconversion, immune system differences, and aluminium concerns in DS.
SECTION 2 Medical studies that show no difference in antibody response (2 studies found)
SECTION 3: additional info, notes, mechanisms for vaccine injury in DS

SECTION 1 – AGAINST
Medical studies that show differences in antibody response (“efficacy”) in people with DS, immune system differences and . (P.S. the term “Effectiveness” is rarely studies, but that is the real world measure of protecton from disease, and is always very much lower than efficacy rate, DS or not). These are only DS specific studies on this page. There are plenty of studies showing general vaccine and vaccine aluminum harms (a range of autoimmune diseases, liver cell and motor neuron cell death and damage, more, all there are non DS specific) in the Files section at Trisomy 21 Research and vaccinepapers.org.

Full text and abstracts available by clicking the blue links.

1) Intrinsic defect of the immune system in children with Down syndrome: a review
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759463/
Clin Exp Immunol. 2009 May; 156(2): 189–193.
doi: 10.1111/j.1365-2249.2009.03890.x
ABSTRACT
Down syndrome (DS) is the most frequent cause of mental retardation in man. Immunological changes in DS have been observed since the 1970s. The neurological system appears to be ageing precociously, with early occurrence of Alzheimer disease; until now, the observed immunological differences have been interpreted in the same context. Looking back at past and present results of immunological studies in DS children in relation to the clinical consequences they suffer, we conclude that it is more likely that the DS immune system is intrinsically deficient from the very beginning.

2) Immune evaluation and vaccine responses in Down syndrome: evidence of immunodeficiency?
http://www.ncbi.nlm.nih.gov/pubmed/21596078
Vaccine. 2011
BACKGROUND:
Patients with Down syndrome (DS) appear to be at a greater risk for serious infections, but it is unclear whether this is due to anatomic variations or intrinsic immune defects.
OBJECTIVE:
We assessed a cohort of pediatric subjects with DS to determine if immunological abnormalities indeed account for the excess infections.
CONCLUSIONS:
Our study suggests that there are subtle abnormalities in both humoral and cellular arms of the immune response in children with DS as compared to the control subjects.

3) Infections and immunodeficiency in Down syndrome
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2249.2011.04335.x/full
Clinical & Experimental Immunology
Volume 164, Issue 1, pages 9–16, April 2011
DOI: 10.1111/j.1365-2249.2011.04335.x
Summary
Down syndrome (DS) is the most common genetic disease and presents with cognitive impairment, cardiac and gastrointestinal abnormalities, in addition to other miscellaneous clinical conditions. DS individuals may have a high frequency of infections, usually of the upper respiratory tract, characterized by increased severity and prolonged course of disease, which are partially attributed to defects of the immune system. The abnormalities of the immune system associated with DS include: mild to moderate T and B cell lymphopenia, with marked decrease of naive lymphocytes, impaired mitogen-induced T cell proliferation, reduced specific antibody responses to immunizations and defects of neutrophil chemotaxis. Limited evidence of genetic abnormalities secondary to trisomy of chromosome 21 and affecting the immune system is available, such as the potential consequences of gene over-expression, most significantly SOD1 and RCAN1. Secondary immunodeficiency due to metabolic or nutritional factors in DS, particularly zinc deficiency, has been postulated. Non-immunological factors, including abnormal anatomical structures (e.g. small ear canal, tracheomalacia) and gastro-oesophageal reflux, may play a role in the increased frequency of respiratory tract infections. The molecular mechanisms leading to the immune defects observed in DS individuals and the contribution of these immunological abnormalities to the increased risk of infections require further investigation. Addressing immunological and non-immunological factors involved in the pathogenesis of infectious diseases may reduce the susceptibility to infections in DS subjects.

Abstracts only available- all are Anti

4) Hepatitis B vaccination in Down’s syndrome and other mentally retarded patients.
Heijtink RA, et al.
Hepatology. 1984 Jul-Aug;4(4):611-4.
http://www.ncbi.nlm.nih.gov/m/pubmed/6235163
Abstract
The immune response after vaccination with H-B-VAX (20 micrograms, Months 0, 1 and 6) was investigated in 23 Down’s syndrome patients and compared to that in 30 other mentally retarded patients and 32 staff members. About 90% of Down’s syndrome and other mentally retarded patients and 100% of staff members had anti-HBs at Month 9, but anti-HBs less than 10 IU per liter were found in 6/23 (26.1%) of Down’s syndrome, 7/30 (23.3%) of other mentally retarded patients, in contrast to 2/32 (6.2%) of staff members. No differences in anti-HBs response with regard to sex and age were observed in staff members, but geometric mean titers of anti-HBs were lower in older Down’s syndrome and other mentally retarded patients, and in male Down’s syndrome patients. Supplementary vaccination is necessary in these individuals to obtain “protective levels” of anti-HBs.
PMID 6235163

5) Aluminum involvement in the progression of Alzheimer’s disease. (note: aluminum adjuvant is in nearly all vaccines)
http://www.ncbi.nlm.nih.gov/pubmed/23380995
J Alzheimers Dis. 2013;35(1):7-43. doi: 10.3233/JAD-121909.
Abstract
The neuroanatomic specificity with which Alzheimer’s disease (AD) progresses could provide clues to AD etiopathology. Magnetic resonance imaging studies of AD clinical progression have confirmed general conclusions from earlier studies of AD neuropathological progression wherein neurofibrillary tangle pathology was observed to spread along a well-defined sequence of corticocortical and corticosubcortical connections, preferentially affecting certain cell types, while sparing others. Identical and non-identical twin studies have consistently shown AD has mixed (environmental and genetic) etiopathogenesis. The decades-long prodromal phase over which AD develops suggests slow but progressive accumulation of a toxic or infective agent over time. Major environmental candidates are reviewed to assess which best fits the profile of an agent that slowly accrues in susceptible cell types of AD-vulnerable brain regions to toxic levels by old age, giving rise to AD neuropathology without rapid neuronal lysis. Chronic aluminum neurotoxicity best matches this profile. Many humans routinely ingest aluminum salts as additives contained in processed foods and alum-treated drinking water. The physical properties of aluminum and ferric iron ions are similar, allowing aluminum to use mechanisms evolved for iron to enter vulnerable neurons involved in AD progression, accumulate in those neurons, and cause neurofibrillary damage. The genetic component of AD etiopathogenesis apparently involves a susceptibility gene, yet to be identified, that increases aluminum absorption because AD and Down syndrome patients have higher than normal plasma, and brain, aluminum levels. This review describes evidence for aluminum involvement in AD neuropathology and the clinical progression of sporadic AD.

6) Safety and effectiveness of an acellular pertussis vaccine in subjects with Down’s syndrome
in Child’s Nervous System
February 1996, Volume 12, Issue 2, pp 100-102
http://link.springer.com/article/10.1007/BF00819505
Abstract
We evaluated the reactogenicity and immunogenicity of an acellular pertussis vaccine in 24 subjects affected by Down’s syndrome and in 10 normal infants. Neither general nor local adverse reactions were observed in either group of subjects. The new acellular vaccine administration elicited protective levels of antibodies in all the subjects with Down’s syndrome, although the geometric mean titres of IgG antibodies againstBordetella pertussis in these subjects were significantly lower than in normal controls.

7) Low hepatitis B vaccine response in children with Down syndrome from Brazil.
Child Care Health Dev. 2014 Jul;40(4):607-9. doi: 10.1111/cch.12099.
http://www.ncbi.nlm.nih.gov/m/pubmed/23952481
Abstract
BACKGROUND:
It has been reported that vaccination against hepatitis B is less effective among people with Down syndrome than in the general population. We aimed to evaluate the rate of seroconversion to hepatitis B vaccine in children with Down syndrome from Brazil.
METHODS:
A total of 120 people with Down syndrome were included. All of them received the vaccine at intervals of 0, 30 and 180 days and serum samples were tested for the presence of antibodies to the hepatitis B surface antigen (anti-HBs) 30 days after the last dose.
RESULTS:
In the studied group, 58.3% (70/120) were male and 41.7% (50/120) female, with the median age of 5 years (range 2-15 years). Fifty-eight of 120 (48.3%) developed anti-HBs after vaccination. No association was found between gender and/or age and vaccine response.
CONCLUSIONS:
The low rate of seroconversion in response to hepatitis B vaccine suggests that all patients with Down syndrome immunized against hepatitis B should be followed and monitored by clinicians.

8: Influenza A/H1N1 vaccination response is inadequate in down syndrome children when the latest cut-off values are used.
http://www.ncbi.nlm.nih.gov/m/pubmed/22986705/
Pediatr Infect Dis J. 2012 Dec;31(12):1284-5. doi: 10.1097/INF.0b013e3182737410.
Abstract
We determined the response of 48 Down syndrome children to 2 doses of influenza A/H1N1 vaccination. Ninety-two percent of the children reached the previously defined protective level (hemagglutination-inhibition titer ≥1:40), but only 27% of the children reached the level of ≥1:110 which was recently described to predict the conventional 50% clinical protection rate in children. Further studies, and potentially adaptations of the schedule, are needed.

9) Decreased response after conjugated meningococcal serogroup C vaccination in children with Down syndrome.
Kusters MA, et al. Pediatr Infect Dis J. 2011.
http://www.ncbi.nlm.nih.gov/m/pubmed/21849866
Abstract
No abstract available
PMID 21849866

10) IgG Subclass Deficiency in Patients with Down’s Syndrome and Aberrant Hepatitis B Vaccine Response
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-3083.1988.tb01477.x/abstract
Abstract
Seventeen adult patients with Down’s syndrome (DS) and 19 adult healthy references were vaccinated with a hepatitis B vaccine in order to study the IgG subclass response. An enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies specific for IgG subclasses was employed. In spite of normal levels of total IgG1 and normal or even high levels of IgG3 in the DS patients, a significantly lower IgG1 response to the vaccine was observed in trisomic patients than in the references.

11) Impaired avidity maturation after tetanus toxoid booster in children with Down syndrome.
Kusters MA, et al. Pediatr Infect Dis J. 2011.
http://www.ncbi.nlm.nih.gov/m/pubmed/21057373
Abstract
Down syndrome children show a decreased avidity of the antibody response after tetanus toxoid booster vaccination at 9 years of age suggesting impaired memory B cell selection in the germinal center. Clinicians need to be aware of this ongoing subtle immunologic deficit in Down syndrome.
PMID 21057373

12) Non-efficacy of low-dose intradermal vaccination against hepatitis B in Down’s syndrome.
Randomized controlled trial
Ahman L, et al. Scand J Infect Dis. 1993.
http://www.ncbi.nlm.nih.gov/m/pubmed/8460344
Abstract
Persons with Down’s syndrome (DS) constitute a risk group for hepatitis B (HB) and are recommended to be immunized. Of 123 persons with DS in Orebro county screened for markers of HB, 31% had such markers; 16% were potentially contagious. 83 persons without markers participated in a comparative trial of the immunogenicity of a recombinant HB vaccine given either intramuscularly (IM) or in a lower dose intradermally (ID). Immunity developed in 73% after IM vaccination as compared to 29% of those given ID vaccination (p < 0.005). At 3-year follow-up half and two-thirds of the immune persons, respectively, had lost their immunity. Those > 30 years had a poor immunization response compared to the younger ones (p < 0.01). Only 19% of the non-responders developed immunity after an IM booster dose given 10 months after the third injection. Intradermal vaccination is not warranted in persons with DS, especially not in middle aged and older persons. A booster dose of vaccine does not ascertain immunity in those who do not respond with immunity to the ordinary immunization schedule. Post-vaccination immunity should therefore be controlled. PMID 8460344

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SECTION 2 PRO

Studies that failed to show differences in Antibody Response (efficacy) in DS (two studies found, abstracts only available) Immunogenicity and safety of an inactivated hepatitis A vaccine in children with Down syndrome. Ferreira CT, et al. J Pediatr Gastroenterol Nutr. 2004.

http://www.ncbi.nlm.nih.gov/m/pubmed/15448421 Abstract OBJECTIVES: Hepatitis A vaccine has not been investigated in children with Down syndrome. The aim of this study was to evaluate immunogenicity and safety of an inactivated hepatitis A vaccine in noninstitutionalized children with Down syndrome and compare their responses to those of healthy control children. METHODS: An open, prospective, controlled trial of 127 children ages 1 to 12 years, 63 with Down syndrome and 64 healthy control subjects, was conducted at a single hospital. Inactivated hepatitis A virus (HAV) vaccine containing 720 enzyme-linked immunosorbent assay units of alum-adsorbed HAV was administered intramuscularly in a two-dose schedule at 0 and 6 months. Seroconversion and anti-HAV titers were measured at months 1 and 7. RESULTS: Seroconversion rates at month 1 were 92% and 94% and geometric mean titers (GMT) were 164.02 and 160.77 mIU/mL in the Down syndrome (DS) and control groups, respectively. At month 7, seroconversion rates were 100% in both groups, with GMT of 1,719.86 and 2,344.90 mIU/mL in the DS and control groups, respectively (P = 0.117). Both doses were well tolerated and no significant adverse events observed. Local reaction at the injection site was the most common adverse event reported in both groups (15% in DS and 11% in controls). CONCLUSIONS: The authors’ data demonstrate a good response to HAV vaccination in children with DS living at home, with GMT not statistically different from that of healthy control children. HAV vaccine is well tolerated and highly immunogenic in children with DS. PMID 15448421

Antibody response to pneumococcal capsular polysaccharide vaccine in Down syndrome patients. Costa-Carvalho BT, et al. Braz J Med Biol Res. 2006. http://www.ncbi.nlm.nih.gov/m/pubmed/17160268

Abstract The majority of children with Down syndrome (DS) tend to have frequent bacterial infections including recurrent respiratory infections. Our objective was to evaluate the production of antibodies to pneumococcal polysaccharide antigens after active immunization in DS subjects. IgG antibodies to pneumococcal serotypes (1, 3, 6B, 9V, and 14) were measured before and 6 weeks after immunization with a 23-valent pneumococcal vaccine (Pneumo23, Pasteur-Merrieux) in 6- to 13-year-old DS children (N = 17) and in aged-matched normal controls (N = 30). An adequate response was defined as a 4-fold increase over baseline or a post-immunization level of specific pneumococcal serotype antibody > or = 1.3 microg/mL. After immunization, all DS children had an increase in post-immunization levels against all serotypes analyzed. A 4-fold or more increase was observed in all DS children concerning serotypes 1 and 14, in 90% of subjects for serotypes 3 and 9V, and in 65% for serotype 6B. Regarding this increase, 8 of the 17 DS children had an adequate response to all serotypes analyzed, 8/17 patients to 4 serotypes and 1/17 to 3 serotypes. However, when we compared post-immunization levels between DS children and controls, we observed lower levels in the former group (P < 0.05) for all serotypes except serotype 3. We conclude that pneumococcal polysaccharide immunization could be beneficial for these DS children.
PMID 17160268

3) Additional info and notes.

One known mechanism of vaccine injury in DS kids. Vaccine aluminum, etc. going directly into the brain.

by Dixie Lawrence, at Trisomy 21 Research

The problem is likely a leaky Blood Brain Barrier. MicroRNA-155, if [even] slightly elevated in a non DS individual causes the BBB to look like Swiss Cheese. In DS, it is over expressed by 51% therefore our children have [severely] Leaky BBB s. This means toxins and heavy metals have direct access to the brain. Resveratrol is a must as it down regulates MicroRNA-155 and reduces I.inflammatory cytokines to the extent that it should repair the BBB. Another issue is the levels of MECP 2 in the brain is too low. Since down regulating MicroRNA-155 upregulates MECP2 often parents see a return or improvement of speech.

CITATIONS
1) CNS Neurol Disord Drug Targets. 2015;14(2):157-67.
The blood-brain barrier in multiple sclerosis: microRNAs as key regulators.
Kamphuis WW, Derada Troletti C, Reijerkerk A, Romero IA, de Vries HE1.
http://www.ncbi.nlm.nih.gov/pubmed/25613507/
Abstract
Multiple sclerosis (MS) is a progressive inflammatory disease of the central nervous system (CNS) leading to severe neurological deficits. To date, no treatment is available that halts disease progression, but clinical symptoms can be generally improved by therapies involving anti-inflammatory and/or immune modulatory reagents, which may cause off-target effects. Therefore, there remains a high and unmet need for more selective treatment strategies in MS. An early event in MS is a diminished function of the blood-brain barrier (BBB) which consists of specialized brain endothelial cells (BECs) that are supported in their barrier function by surrounding glial cells. Leakage and inflammation of the BECs in MS patients facilitate the massive influx of leukocytes into the brain parenchyma, which in turn induces irreversible demyelination, tissue damage and axonal dysfunction. Identification of ways to restore BBB function and promote its immune quiescence may therefore lead to the development of novel therapeutic regimes that not only specifically reduce leukocyte entry into the central nervous system but also restore the disturbed brain homeostasis. However, the complex network of molecular players that leads to BBB dysfunction in MS is yet to be fully elucidated. Recent discoveries unravelled a critical role for microRNAs (miRNAs) in controlling the function of the barrier endothelium in the brain. Here we will review the current knowledge on the involvement of BBB dysfunction in MS and the central role that miRNAs play in maintaining BBB integrity under inflammatory conditions.

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