The Vaccine-Autism Link. Maybe the parents aren’t so crazy…

This is a supplemental article to “Dear Robert De Niro You’re not Wrong to want more conversation about Autism (and Vaccines)

In a previous article I asked several questions:

  • Is autism a stress-impacted early and pre-life programming?
  • If it is, are children with autism over-reacting to stressors in their environment?
  • Could a vaccine be a stressor that creates a regression in a small minority?
  • I also asked the question if we take a stress approach can we improve both the efficacy of the vaccination program and prevent this hyper-programming?

 

needle

 

What Are Toxins?

A toxin is typically thought of as a skull and crossbones, something that can kill you.  A toxin has what is called an LD50, that is the amount that will kill half (50%) of the population of species it is exposed to. Toxins typically have a very specific mechanism of action unique to the toxin. Which is why, just like snake venom has an anti-venom, a toxin has an antitoxin. Antitoxins are antibodies (or proteins) produced by the body that counteract a toxin. However, anything, even something as essential as water, can be toxic at excessive amounts. That is a different mode of toxicity. For that mode of toxicity anything can be a toxin if it overwhelms our body’s ability to process, absorb, balance, metabolize or eliminate it. Most substances that go by the term “toxin” however, have very specific action of detriment. There are over 700 known toxins.

Primary and Secondary Actions

There are two different ways to look at toxins. The typical toxicology as stated above is that a toxin can kill you. This is the primary action of a toxin, the very direct and linear action. There are also secondary actions of toxins. This is both the amount of oxidative (or nitrosatic) stress the toxin creates in the body AND also how the body senses and reacts to the toxin. When the body senses that a toxin becomes a threat to the system it creates a stress adaptation response. The primary action of a toxin is subdued by an antitoxin, but the secondary action of a toxin is subdued by adaptation, stress reactions and antioxidants.

The differences between linear and nonlinear approaches

It also helps to understand that there are generally two major ways to approach scientific problems. One is call a linear approach and the other is a nonlinear approach. As you might be able to infer from the names one is very straight and direct and the other is much more inclusive of multiple variables and outcomes. Much like the primary and secondary actions of toxins.

The nonlinear approach not only looks at multiple variables but also looks for initial conditions (individual differences). In a nonlinear perspective one cause could lead to many outcomes, whereas in a linear perspective we expect one cause to have the same outcome.

In a linear model of toxicity there is primary and single source and action of a toxin. We measure when that substance becomes dangerous via the rule of thumb of “the dose makes the poison”. The higher the dose the greater the impact, below a certain point there would be no impact. That is a linear model. As the dose goes up, the influence goes up. A linear perspective tells us that a certain amount is toxic.

Whereas a nonlinear model of toxicity the amount is more variable depending on the state of the system, timing of the assault, gender of the individual, the nutritional state and  current state of epigenetic programming. Epigenetic programming can come from earlier or before life. An earlier stress can create a greater response to future stresses.  This is described in research showing that multiple “hits” to a system can create greater reactions to otherwise innocuous stresses.

A nonlinear perspective tells us that toxicity depends on the person and the situation as to what amount is toxic.In a nonlinear model we look at the action from a stress perspective.

Much of the problem here is that we don’t have a framework for stress mechanisms, mostly because current mainstream medicine takes a linear approach to disorders. Stress is nonlinear concept. So we are very absent in our ability to communicate about this next level of science… but we are getting closer.  So let’s keep trying here, because nonlinear models are very important for understanding autism and stress adaptation disorders.

Nonlinear Systems from Wikipedia:

Nonlinear problems are of interest to engineers, physicists and mathematicians and many other scientists because most systems are inherently nonlinear in nature. As nonlinear equations are difficult to solve, nonlinear systems are commonly approximated by linear equations (linearization).

This is an important concept because linear solutions aren’t wrong necessarily, they just aren’t whole answers. They are parts of a larger whole.

Definition of Linear vs Nonlinear Dynamics from the Free Dictionary:

Unlike a linear system, in which a small change in one variable produces a small and easily quantifiable systematic change, a nonlinear system exhibits a sensitive dependence on initial conditions: small or virtually unmeasurable differences in initial conditions can lead to wildly differing outcomes.

Stress is a framework. We all handle a particular stress differently, and what becomes stressful depends on many variables.

Thimerosal: The Toxin in the Vaccine-Autism Debate

The most likely culprit in the vaccine-autism debates was a perservative called Thimerasol, or ethyl-mercury. And most studies that are used to announce that vaccines are not associated with autism use mercury as its subject.

Is it a toxin? Or does it have stress toxic effects?

Let’s explore some of the studies cited on vaccine safety (Thompson 2007, Heron 2004, Andrews 2004) and see if they represent a linear toxicity. Linear toxicity is where the substance has no effect below a certain point for most of the population, but becomes toxic as the dosage increases (following “the dose makes the poison” doctrine).

THOMPSON 2007: “Results were equally divided between positive and negative effects”

HERON 2004: “Results of this study were contrary to expectation, it was common for the unadjusted results to suggest a beneficial effect of thimerosal exposure.”

ANDREWS 2004.”Except for Tics, larger doses of TMR had lesser impact. Hence a positive association.”

Thimerosal Exposure in Infants and Developmental Disorders: A Retro…”)…

Andrews

These Clearly Show a Hormetic Response. What’s a Hormetic Response?

Here we see that thimerosal might indeed have a hormetic response, or appear to have a positive income on the cognition of children. This is because their bodies are reacting and adapting positively to a toxin as a stress to the body. When we see positive impacts at lower levels this would mean we would have to be in a nonlinear framework to interpret the results correctly. A linear interpretation would be that it doesn’t have a toxic effect (since it doesn’t do damage) and that the positive effects would be an artifact, something we could just dismiss as having no meaning. And therefor conclude vaccines have no association to autism. But if we instead assume this could represent hormesis, then we can look at the results of these studies to mean instead that there could be an association because the vaccines, or the thimerosal, created stress. As a potential neurotoxin, thimerosal’s impact can depend on the activation or presence of antioxidant systems.

Hormesis

Hormesis is a biological phenomenon whereby a beneficial effect (improved health, stress tolerance, growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses

In a nonlinear interpretation, a neurotoxin could have a positive effect with lessor amounts depending on a variety of factors.

What this evidence may suggest (not that more is better) rather that the potential relationship between vaccines and autism and any number of xenobiotic stresses need to be evaluated in subclinical toxicity: according to timing (age), dosage (high or low), the person’s genetic makeup (metabolism and nutritional status), other confounders and the current state (mental/physical stress) of the individual.

The stress of heavy metals can create an adaptive stress response in some that are exposed. Metals and many neurotoxins have stress effects and follow the rules of stress. So when we see cognitive ‘improvement’ from mercury (instead of no effect) we know we are looking at a stress and nonlinear model of interpretation instead of a “dose makes the poison” linear impact. (We are not looking at vaccines as a toxin, we are looking at vacccines as a stressor).  This might give us an entirely new interpretation of the information and studies at hand. Instead of “no association” the association would be that those vaccines had the potential to create stress. For some this would be positive, but for others it could be negative. That would be the information we’d need to tease from the research. If vaccines create stress and autism is already an overly sensitive programmed reaction to stressors, could a vaccine create regression in some sensitive subpopulations?

What is Autism?

 From a stress perspective:

The consensus agrees that autism is a gene-environment interaction. Autism is in a way is “caused” by stress, in that stresses act on a system and that systems particular method of sensitivity and adaptation creates trade-offs. We see Autism and developmental delays. It “amps-up” processes and trade-offs in systems that are hit by early life or before life stress. The diagram below is from researchers in Australia trying to give us an idea of the complications involved when it comes to the multitude of factors coming together to create autism.

The Role of Epigenetic Change in Autism Spectrum Disorders
epigenetic loads

Early life stress or exposure can be related to many adult mental and metabolic issues.   As part of nonlinearity, many of the same factors of stress can lead to many outcomes (not just autism).  Whereas autism programming would have likely occurred earlier, so it would be fair to say that it is highly unlikely that alone any early life stress could create autism.

Vaccines, however likely or unlikely, could, in the combination with many other factors, be a stress that creates a regression. What those parents experience after a vaccination could have been a real experience, however, it doesn’t mean that the vaccine was a cause, it would rather be more likely that other factors made an innocuous and beneficial stressor too stressful at that time and context.

Could vaccines be one of innumerable different stresses that in combination, under certain circumstances, create the outcome of Autistic regression after a stress?

We could continue to be investigate and include or eliminate the possibility by first asking the right questions and evaluating it in the proper context of Autism causation.

What factors influence a vaccines success (inoculation to disease) and what could make a vaccine more stressful?

From “Immune System and Vaccination”

Many factors may influence the immune response to vaccination. These include the presence of maternal antibody, nature and dose of antigen, route of administration, and the presence of adjuvants (e.g., aluminum-containing materials added to improve the immunogenicity of the vaccine). Host factors such as age, nutritional factors, genetics, prolonged psychological stress and coexisting disease, may also affect the response.

RESOURCES IMPACTING VACCINATION

  • Social resources like hugs and distraction in infants after pain can help reset excessive pain reprogramming
  • The Microbiome and microbes
  • Essential fatty acids
  • Vitamin D, K, and A
  • Hormones in men and women
  • Time of Day
  • Melatonin
  • Selenium and other minerals
  • Mothers Antibodies from her own vaccination can create greater chance of early life  spread of disease because the infant is left more vulnerable.
  • Stress and our current immune functioning

The Autism-Vaccines Arguments

Let’s take another look from a Stress Perspective. There are many comments around the internet that say the questions about vaccines have been asked and answered

In our medical model we rely almost exclusively on a linear model approach to diseases. We used the logic and rules of what is referred to as “Koch’s Postulates“; that diseases come from a single cause, effect everyone it comes in contact with and to find the cause we find the same culprit in everyone.

Now that we know we need to use a NONLINEAR approach let’s take another look at these statements and assertions about the vaccine-autism links.

  • Correlation is NOT Causation

This is actually derived from the quote “correlation does not imply causation.”

A correlation study is something done typically after the evidence has been collected to suggest there might be a connection. Then this larger observation study of a large group is undergone to test to see if the indeed cause creates a reaction (even in a small minority). Correlation studies are incredibly important to scientific validation because if it seems there could be an association then a correlation epidemiological study should show that there is an association (shown by corresponding rising numbers). However, many large epidemiological studies are contingent upon certain variables being held constant, or that there is linearity assumed that if it is a cause there is a single causal factor. Once we know that the cause in nonlinear however, epidemiological studies will need to be further refined. instead of studying “as large as possible” correlation groups, we will need to study very specific factors in combination of smaller groups and smaller studies. These types of studies accuracy depends solely upon if you are controlling for the correct factors. The studies definitely prove vaccines are not a single cause, but they have yet to study if vaccines are being impacted by stress and if the stress of a vaccine can simulate regression.

  • I have six children. They all had vaccines. Only one has autism. Therefore vaccines do not cause autism.

Again, this is great logic for single source causation. If vaccines were the cause for autism, then this would be a way to prove it doesn’t. However, if we are assuming that autism is a gene-environment interaction and assume further that it is a stress-reactivity programming disorder, we’d have to look at this differently.  It may be that only one child had the multiple factors involved.

  • My husband has autism traits and my son has autism. Therefore its genetic. Nothing causes it but “being born“.

This is again true if there were a single cause of autism. But we know now that it is more complex and there is no “gene” or single genetic pattern that causes autism, rather that there is some interaction with the environment in susceptible populations. We may see the traits in the generation before, but we could very well be experiencing the greater dysfunctional aspects of those genetic traits in the current population. It shows us for certain that vaccines are not the cause, but it does not answer the question if for some, if the amplification of reactivity could either influence the effect of the vaccination or if the vaccination further influences that programming.

  • The Science has Spoken. Vaccines have NOTHING to do with Autism.

Science isn’t a God that gives us absolute answers. Science is a set of rules used to discover truth. A series of questions with evidence to support it. A sense of logical progression that creates a larger story of reason. The consensus of scientific minds can look at the same information and come to the same conclusion, that vaccines don’t cause autism, because they all follow the same rules for causation. The problem is, the set of rules they are following are for single source causation.

  • Those parents are CRAZY. The regression just HAPPENS to be at the same time of the vaccination. Correlation is not Causation.

 Correlation, a regression after a vaccination, even if the vaccine created the regression STILL wouldn’t mean that the vaccine was the “cause”. Because the cause would be a combination of many factors. But ultimately the cause of a regression would be stress. A growth spurt (like going from crawling to walking per se) is stressful on the body/mind because it is a drain on resources. So we’d have to ask if vaccines are enough of a stress during a growth spurt that for some they could be enough to create an additional burden for regression. That could still ultimately mean the genetics or the growth spurt was the “cause” of the susceptibility. But either way if we see a regression, we know its stress, we can start doing something about it. If we see autism as a hyper-sensitivity to the environment we could question whether an autistic individual is more susceptible to the type of stress a vaccination would create. Just as we could question why when there is a growth spurt around the same time we also see regression (in certain subtypes). Can this be caused by any kind of early life stress because of a more fragile brain?

  • There is only ONE study that associated vaccines with Autism and that guy is a fraud.

Andrew Wakefield has become the poster child windmill that all of science can point their finger at. But in reality it was the thousands of parents that noticed this observation. After vaccinations their kids seemed to regress. Its also false that there are millions of studies to show vaccine safety and only this one to show a  connection. There are many animal and in the lab studies that show the potential negative impact of thimerosal (mercury) and vaccines to later life issues.

Stress can also alter antibody response and decrease the efficacy of vaccination and protection. “Stress affects antibody responses in different ways depending on the type and duration of the stressor, its context and meaning for the individual. The most common effect is immune depression, and some of the effects appear to be mediated by the classical stress hormones of the hypothalamic-pituitary-adrenal axis.” (Booth 2007). So Dr. Offit asserting that we have plenty of antibodies is a linear assumption. That the only thing that matters is the number, but from a nonlinear perspective we ask do we have the ability to create and utilize those antibodies. At what point does using or creating too many antibodies become stressful?

“Logic is a systematic way of coming to the wrong conclusion with confidence.” ~Murphy’s Law

(Edited May 7th, 2016 )

If we take a stress approach can we improve both the efficacy of the vaccination program and prevent this hyper-programming?

Question: So if vaccines are a stress, can we just delay and spread them out?

My answer: No, avoiding stress isn’t the solution, measuring and making us more resilient to such minor stress and aware of stress mechanisms would be.

I talk about the mistakes of a linear perspective in guiding our solutions. Getting rid of toxins (ie “clean vaccines” or no vaccines) or lessening the burden by spacing shots out may be a similar mistake. Granted too great of a toxin burden at any one time is problematic. However, the problem with this line of reasoning from, lets call them “vaccine advocates”, is that there is no evidence that they are generally excessive. And further, spacing out shots could interfere with producing adequate and timely immunity. Not to mention theoretically spacing shots more often may create more stress programming and reactivity opportunity (3-hit concept).

The problem with the argument between the pro-vaccine and “safe”-vaccine advocates is that it is black and white. Pro-vaccine states there is no way there are enough toxins, and the vaccine advocates say any toxin is bad. Herein lies many problems. First, these are two extreme linear arguments. The nonlinear approach to vaccines is in the in-between space, when and why do vaccines becomes stressful?

Instead getting rid of the burden we would look rather to how to make individuals more resilient to stress and create tests for both resiliency and reactivity after vaccination for those with concerns.

The argument I hear most often against this is that it is unfeasible or too expensive. What are the costs for not vaccinating a population? What are the costs of creating a stressor that impairs even a small percent of the population? Besides these type of tests are becoming more available and possible every year. Some may even believe becoming necessary to prevent reactions in those that are genetically, epigenetically  or nutritionally primed to over-react to stresses and particular toxins.

This would simply mean lets test the major stress and detoxification channels before and after vaccination on those that may be susceptible or parents that may be wary for good reason. The more we know the better.

So we test biomarkers before and after shots like antioxidant activity, fatty acids, vitamin D & A, microbiota balances, stress reactivity (cortisol and HPA), neuroendocrine function and genetic detoxification. Then after vaccines take the same to see if any have been compromised and reverse if possible.

Could that be the compromise to mandatory vaccination and/or exemptions? I’d like to see the conversations happen.


 References and Further Reading

“Extraordinary claims require extraordinary evidence” ~Carl Sagan

Early Life Stress Later Life Outcomes

This can’t be stressed enough: The contribution of select environmental toxicants to disruption of the stress circuitry and response. http://www.ncbi.nlm.nih.gov/pubmed/26409212

Early-life stress, HPA axis adaptation, and mechanisms contributing to later health outcomes. http://journal.frontiersin.org/article/10.3389/fendo.2014.00073/full

Phenotypic plasticity in development and evolution: facts and concepts http://rstb.royalsocietypublishing.org/content/365/1540/547

Hormesis is central to toxicology, pharmacology and risk assessment. http://www.ncbi.nlm.nih.gov/pubmed/20332169

“The Three-Hit Concept of Vulnerability and Resilience: Towards Understanding Adaptation to Early-Life Adversity Outcome.” Psychoneuroendocrinology 38.9 (2013): 1858–1873. PMC. Web. 29 Apr. 2016.Daskalakis, Nikolaos P. et al. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773020/

The Long-term Impact of Stress During Childhood on Brain Development http://www.schizophrenia.com/sznews/archives/005836.html

Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks. Chen Y1, Baram TZNeuropsychopharmacology. 2016 Jan;41(1):197-206. doi: 10.1038/npp.2015.181. Epub 2015 Jun 24. http://www.ncbi.nlm.nih.gov/pubmed/26105143

Stress and drugs permanently alter brain development http://www.futurepundit.com/archives/001787.html

Influence of early life stress on later hypothalamic–pituitary–adrenal axis functioning and its covariation with mental health symptoms: A study of the allostatic process from childhood into adolescence http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3266106/

Prenatal Programming of Mental Illness: Current Understanding of Relationship and Mechanisms http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4458064/

Risk of Psychiatric and Neurodevelopmental Disorders Among Siblings of Probands With Autism Spectrum Disorders. Jokiranta-Olkoniemi E1, Cheslack-Postava K2, Sucksdorff D JAMA Psychiatry. 2016 May 4. doi: 10.1001/jamapsychiatry.2016.0495. http://www.ncbi.nlm.nih.gov/pubmed/27145529

Linking Mitochondria to Synapses: New Insights for Stress-Related Neuropsychiatric Disorders http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4738951/

Interpreting ‘Dose-Response’ Curves Using Homeodynamic Data: With an Improved Explanation for Hormesis http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754536/

Environmental factors in the development of autism spectrum disorders.
Sealey LA1, Hughes BW1, Sriskanda AN1, Guest JR1, Gibson AD1, Johnson-Williams L1, Pace DG2, Bagasra O3.Environ Int. 2016 Mar;88:288-98. doi: 10.1016/j.envint.2015.12.021. Epub 2016 Jan 28. http://www.ncbi.nlm.nih.gov/pubmed/26826339

Environmental factors in the development of autism spectrum disorders: A reply to Sealey et al. (2016). Fluegge K1.Environ Int. 2016 Feb 26. pii: S0160-4120(16)30060-5. doi: 10.1016/j.envint.2016.02.024 http://www.ncbi.nlm.nih.gov/pubmed/26926711

Prenatal and Early Life Exposure to Stressful Life Events and Risk of Autism Spectrum Disorders: Population-Based Studies in Sweden and England http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0038893#s4 We found no evidence to support the hypotheses that exposure to stressful life events during the prenatal period is associated with an increased risk of offspring ASD.

Immune Changes Linked to Regression, GI Distress & Repetitive Behaviors 
https://www.autismspeaks.org/science/science-news/immune-changes-linked-regression-gi-distress-repetitive-behaviors

Transgenerational effects of social stress on social behavior, corticosterone, oxytocin, and prolactin in rats http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076950/

Stress and the social brain: behavioural effects and neurobiological mechanisms http://www.nature.com/nrn/journal/v16/n5/abs/nrn3918.html

Comparing Cortisol, Stress and Sensory Sensitivity in Children with Autism http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2698454/

Atypical sympathetic arousal in children with autism spectrum disorder and its association with anxiety symptomatology. Panju S, et al. Mol Autism. 2015. http://www.ncbi.nlm.nih.gov/m/pubmed/26693000/

Stress-induced perinatal and transgenerational epigenetic programming of brain development and mental health http://www.sciencedirect.com/science/article/pii/S0149763414003091

The Role of Epigenetic Change in Autism Spectrum Disorders http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443738/

The Relationship between Stress and Social Functioning in Adults with Autism Spectrum Disorder and without Intellectual Disability http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412754/

Social-cognitive, physiological, and neural mechanisms underlying emotion regulation impairments: Understanding anxiety in autism spectrum disorder http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4180783/

A Review of Rhythm and Responsiveness of Cortisol in Individuals with Autism Spectrum Disorders http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4165710/

Neonatal Amygdala Lesions Lead to Increased Activity of Brain CRF Systems and Hypothalamic-Pituitary-Adrenal Axis of Juvenile Rhesus Monkeys http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138348/

Prenatal Stress and Risk for Autism http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2632594/

Pathway Network Analyses for Autism Reveal Multisystem Involvement, Major Overlaps with Other Diseases and Convergence upon MAPK and Calcium Signaling. Ya Wen, Mohamad J. Alshikho, Martha R. Herbert. PLOS ONE, 2016; 11 (4): e0153329 DOI: 10.1371/journal.pone.0153329

Ritual circumcision linked to increased risk of autism in young boys, research suggests. http://www.sciencedaily.com/releases/2015/01/150109093725.htm “Possible mechanisms linking early life pain and stress to an increased risk of neurodevelopmental, behavioural or psychological problems in later life remain incompletely conceptualised”. Professor Morten Frisch of the Statens Serum Institut, Copenhagen, who led the research, said: “Our investigation was prompted by the combination of recent animal findings linking a single painful injury to lifelong deficits in stress response and a study showing a strong, positive correlation between a country’s neonatal male circumcision rate and its prevalence of ASD in boys.”

Study Finds Children with Autism Have More Active Adaptive Immune System New Research May Also Identify Potential Mechanism for Immune Dysregulation in Autism http://www.autismspeaks.org/science/science-news/study-finds-children-autism-have-more-active-adaptive-immune-system In an intriguing twist, although baseline levels of almost all the cytokines measured were higher in children with autism than in control individuals, Dr. Molloy found an exception in the relatively lower levels of the critical regulatory cytokine, IL-10, in individuals with autism. If both Th1 and Th2 cells are just generally overactive in individuals with autism, elevated IL-10 production would have been predicted as well.

Thimerosal (ethyl-mercury)

Dose-response analysis indicating time-dependent neurotoxicity caused by organic and inorganic mercury-Implications for toxic effects in the developing brain.
Pletz J1, Sánchez-Bayo F2, Tennekes HA3. Toxicology. 2016 Mar 10;347-349:1-5. doi: 10.1016/j.tox.2016.02.006. Epub 2016 Mar 2. http://www.ncbi.nlm.nih.gov/pubmed/26945727

Thimerosal neurotoxicity is associated with glutathione depletion: protection with glutathione precursors. http://www.ncbi.nlm.nih.gov/pubmed/15527868

Neurodevelopment of Amazonian children exposed to ethylmercury (from Thimerosal in vaccines) and methylmercury (from fish).  Marques RC1, Abreu L2, Bernardi JV3, Dórea JG4.Environ Res. 2016 Jan 7. pii: S0013-9351(15)30184-5. doi: 10.1016/j.envres.2015.12.022.http://www.ncbi.nlm.nih.gov/pubmed/26774584

Dose-response analysis indicating time-dependent neurotoxicity caused by organic and inorganic mercury-Implications for toxic effects in the developing brain.
Pletz J1, Sánchez-Bayo F2, Tennekes HA3.Toxicology. 2016 Mar 10;347-349:1-5. doi: 10.1016/j.tox.2016.02.006. Epub 2016 Mar 2. http://www.ncbi.nlm.nih.gov/pubmed/26945727

Alternatively Spliced Methionine Synthase in SH-SY5Y Neuroblastoma Cells: Cobalamin and GSH Dependence and Inhibitory Effects of Neurotoxic Metals and Thimerosal. http://www.ncbi.nlm.nih.gov/pubmed/26989453

Low-dose mercury exposure in early life: relevance of thimerosal to fetuses, newborns and infants. http://www.ncbi.nlm.nih.gov/pubmed/23992327

Integrating experimental (in vitro and in vivo) neurotoxicity studies of low-dose thimerosal relevant to vaccines. http://www.ncbi.nlm.nih.gov/pubmed/21350943

123 Studies of Vaccine reactions http://textsheet.com/wp-content/uploads/2015/11/220807175-123-Research-Papers-Supporting-the-Vaccine-Autism-Link.pdf

The challenge of assessing infant vaccine responses in resource-poor settings
Katie L Flanagan, Sarah Burl, Barbara L Lohman-Payne, and Magdalena Plebanski. Expert Rev Vaccines. 2010 Jun; 9(6): 665–674. doi: 10.1586/erv.10.41
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2937226/

Multidimensional response to vaccination pain in very preterm, moderate- to-late preterm and full-term infants at age three months.
Mehler K1, Ulbrich L2, Börner S2,Early Hum Dev. 2015 Mar;91(3):199-204. doi: 10.1016/j.earlhumdev.2015.01.011. Epub 2015 Feb 14. LINK

Effect of influenza vaccine on markers of inflammation and lipid profile.
Tsai MY1, Hanson NQ, Straka RJ, J Lab Clin Med. 2005 Jun;145(6):323-7. http://www.ncbi.nlm.nih.gov/pubmed/15976761

Potential Use of Salivary Markers for Longitudinal Monitoring of Inflammatory Immune Responses to Vaccination. Lim PW1, Garssen J2, Sandalova E3.Mediators Inflamm. 2016;2016:6958293. doi: 10.1155/2016/6958293. Epub 2016 Feb 28. http://www.ncbi.nlm.nih.gov/pubmed/27022211

Possible Triggering Effect of Influenza Vaccination on Psoriasis.
Gunes AT1, Fetil E1, Akarsu S1,J Immunol Res. 2015;2015:258430. doi: 10.1155/2015/258430. Epub 2015 Aug 25. http://www.ncbi.nlm.nih.gov/pubmed/26380315

C-reactive protein response to influenza vaccination as a model of mild inflammatory stimulation in the Philippines. McDade TW1, Borja JB2, Kuzawa CW.  Vaccine. 2015 Apr 21;33(17):2004-8. doi: 10.1016/j.vaccine.2015.03.019. Epub 2015 Mar 18. http://www.ncbi.nlm.nih.gov/pubmed/25795257

Elevated maternal C-reactive protein and autism in a national birth cohort.
Brown AS1, Sourander A2, Hinkka-Yli-Salomäki S3, Mol Psychiatry. 2014 Feb;19(2):259-64. doi: 10.1038/mp.2012.197. Epub 2013 Jan 22.

Embryonic exposure to thimerosal, an organomercury compound, causes abnormal early development of serotonergic neurons. http://www.ncbi.nlm.nih.gov/pubmed/21669256

5-HTT Serotonin Gene and Autism http://www.dnalc.org/view/918-5-HTT-Gene.html

Persistent behavioral impairments and alterations of brain dopamine system after early postnatal administration of thimerosal in rats. http://www.ncbi.nlm.nih.gov/pubmed/21549155

Neonatal administration of a vaccine preservative, thimerosal, produces lasting impairment of nociception and apparent activation of opioid system in rats. 2010 http://www.ncbi.nlm.nih.gov/pubmed/19747466 2011 http://www.ncbi.nlm.nih.gov/pubmed/20803069

Activation of methionine synthase by insulin-like growth factor-1 and dopamine: a target for neurodevelopmental toxins and thimerosal. http://www.ncbi.nlm.nih.gov/pubmed?term=thimerasol+folate

Chronic low-level mercury exposure, BDNF polymorphism, and associations with cognitive and motor function. http://www.ncbi.nlm.nih.gov/pubmed/16301096

Integrating experimental (in vitro and in vivo) neurotoxicity studies of low-dose thimerosal relevant to vaccines. http://www.ncbi.nlm.nih.gov/pubmed/21350943

Luteolin and thiosalicylate inhibit HgCl(2) and thimerosal-induced VEGF release from human mast cells. http://www.ncbi.nlm.nih.gov/pubmed/21244751

Lasting neuropathological changes in rat brain after intermittent neonatal administration of thimerosal. http://www.ncbi.nlm.nih.gov/pubmed/21225508

The association between serotonin transporter gene promotor polymorphism (5-HTTLPR) and elemental mercury exposure on mood and behavior in humans.J Toxicol Environ Health A. 2010;73(15):1003-20. http://www.ncbi.nlm.nih.gov/pubmed/20526950

Impact of Lead, Manganese and Mercury: Early exposure impacts later in life http://www.hindawi.com/journals/ijad/2011/607543/

Longitudinal associations of age and prenatal lead exposure on cortisol secretion of 12-24 month-old infants from Mexico City. http://www.ncbi.nlm.nih.gov/pubmed/26926653

Embryonic exposure to thimerosal, an organomercury compound, causes abnormal early development of serotonergic neurons. http://www.ncbi.nlm.nih.gov/pubmed/21669256

Persistent behavioral impairments and alterations of brain dopamine system after early postnatal administration of thimerosal in rats. http://www.ncbi.nlm.nih.gov/pubmed/21549155

Increased susceptibility to ethylmercury-induced mitochondrial dysfunction in a subset of autism lymphoblastoid cell lines. Rose S1, Wynne R1, Frye RE1, Melnyk S1, James SJ1. J Toxicol. 2015;2015:573701. doi: 10.1155/2015/573701. http://www.ncbi.nlm.nih.gov/pubmed/25688267

 

NUTRITION

Host nutritional status: the neglected virulence factor Melinda A. Becka, Jean Handyb and Orville A. Levander Trends in Microbiology, Volume 12, Issue 9, 417-423, 1 September 2004 doi:10.1016/j.tim.2004.07.007 http://www.cell.com/trends/microbiology/abstract/S0966-842X(04)00164-7 These systems work together to first activate and amplify local inflammatory responses that contain or eliminate invading pathogens, and subsequently to terminate inflammation and restore host homeostasis.

Dietary Fatty Acids and Immune Response to Food-Borne Bacterial Infections
Lisa M. Harrison,* Kannan V. Balan, and Uma S. BabuNutrients. 2013 May; 5(5): 1801–1822.
Published online 2013 May 22. doi: 10.3390/nu5051801 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708349/

Dietary fatty acids affect the immune system in male mice sensitized to ovalbumin or vaccinated with influenza. Hogenkamp A, van Vlies N, Fear AL, van Esch BC, Hofman GA, Garssen J, Calder PC. J Nutr. 2011 Apr 1;141(4):698-702. doi: 10.3945/jn.110.

Nutritional Status in Relation to the Efiicacy of the Thesus-Human Reassortant, Tetravalvent Rotavirus Vaccine (RRV-TV) in Infants from  Belem, Para State, Brazil
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0036-46652002000100003

Evaluation of Immune Response in Infants with Different Nutritional Status: Vaccinated Against Tuberculosis, Measles and Poliomyelitis
http://tropej.oxfordjournals.org/cgi/content/abstract/40/6/345?ck=nck
The influence of marginal zinc deficient diet on post-vaccination immune response against hepatitis B in rats. Hepatology Research, Volume 35, Issue 1, Pages 26-30
F. Ozgenc, G. Aksu, F. Kirkpinar, İ. Altuglu, I. Coker, N. Kutukculer, R. Yagci

Measles related complications and the role of vitamin A supplementation. http://www.ncbi.nlm.nih.gov/pubmed/18568439

Vaccines and Vitamin A

Something that important regulates gene and body programming (a lack of Vitamin A gets the body to store more fat reserves). However, as we know, Vitamin A is something we absolutely do not want too much of. Like many resources it can be a both a pro- and anti-oxidant. This is why its not about stress or things like fat resources not being good or bad per se but about a balance and programming. When there is a disruption of homeostatic balances  these are not easily fixed (like an ecosystem, once disrupted, putting back the deficiency doesn’t always “fix” it, once started) from these resources of stress resiliency.  If we think of primal resources we had available that built our immune systems and internal structural integrity; animal sources of protein and fat were staples in most cultures.  Outside influences, like illnesses, can also suck up our Vitamin A reserves. Which will heighten our immune responsivity. This is where it gets confusing. We want strong immune responses, but we don’t want over-programming or wearing down aspects from immune responsivity. So too low or too high levels can mess things up. Diseases like the measles can also lower Vitamin A levels (measles also impacts oxidative status, also merits consideration of microbiotic status, in oxidative status, for better seroconversion or prevent over-reactivity of immune to vaccination in the case of allergies)

One problem with stress is that what is considered stressful is dependent upon the “oxidative structure” of the person. Not necessarily weak or strong, but merely different things are uniquely stressful depending on the person’s own stress structure. A primary stress differential is sexual dimorphic stress reactivity. Possibly dependent upon unique brain structures and diversity of strengths. Which coordinates with immune strengths and resource needs.

So from a stress-balancing perspective of trade-offs, when something enhances a “good” aspect, it can also enhance “bad” aspects.  This will be more prominent in a manner depending on estrogen/testosterone functioning. Which is why we see differential, sexual dimorphic, influences. For vaccines like measles, the vaccine can have “non-specific” effects. Meaning it can impact the immune system more generally. This can be good or bad depending on the system. For girls, an interaction with vitamin A with Measles vaccine has shown higher mortality rates.

Melatonin and Vitamin D (Sunlight)

BCG Vaccination: A Role for Vitamin D? http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031626/

Vitamin effects on the immune system: vitamins A and D take centre stage http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906676/

Melatonin: buffering the immune system. Carrillo-Vico A1, Lardone PJ, Alvarez-Sánchez N, Rodríguez-Rodríguez A, Guerrero JM. Int J Mol Sci. 2013 Apr 22;14(4):8638-83. doi: 10.3390/ijms14048638. http://www.ncbi.nlm.nih.gov/pubmed/23609496

Melatonin modulates a wide range of physiological functions with pleiotropic effects on the immune system. Despite the large number of reports implicating melatonin as an immunomodulatory compound, it still remains unclear how melatonin regulates immunity. While some authors argue that melatonin is an immunostimulant, many studies have also described anti-inflammatory properties. The data reviewed in this paper support the idea of melatonin as an immune buffer, acting as a stimulant under basal or immunosuppressive conditions or as an anti-inflammatory compound in the presence of exacerbated immune responses, such as acute inflammation. The clinical relevance of the multiple functions of melatonin under different immune conditions, such as infection, autoimmunity, vaccination and immunosenescence, is also reviewed.

Maternal melatonin communicates daylength to the fetus in Djungarian hamsters. http://www.researchgate.net/publication/19380489_Maternal_melatonin_communicates_daylength_to_the_fetus_in_Djungarian_hamsters

Vaccination prepartum enhances the beneficial effects of melatonin on the immune response and reduces platelet responsiveness in sheep http://www.biomedcentral.com/1746-6148/8/84

The use of melatonin as a vaccine agent. http://www.ncbi.nlm.nih.gov/pubmed/16055232

Melatonin prevents neonatal dexamethasone induced programmed hypertension: Histone deacetylase inhibition. http://www.sciencedirect.com/science/article/pii/S0960076014001320

Advances in the Research of Melatonin in Autism Spectrum Disorders: Literature Review and New Perspectives http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3821628/

Th1 and Th2 Chemokines, Vaccine-Induced Immunity, and Allergic Disease in Infants After Maternal Omega-3 Fatty Acid Supplementation During Pregnancy and Lactation http://www.nature.com/pr/journal/v69/n3/full/pr9201149a.html

Perinatal programming of murine immune responses by polyunsaturated fatty acids. http://www.ncbi.nlm.nih.gov/pubmed/25140925

STRESS

The clear conclusion, as reported in the Journal Brain, Behavior and Immunity, is these vaccines are less effective on a stressed-out population. http://jap.physiology.org/cgi/content/full/82/5/1385

Psychological stress and antibody response to influenza vaccination: when is the critical period for stress, and how does it get inside the body? http://www.ncbi.nlm.nih.gov/pubmed/15039506

Psychological stress and antibody response to influenza vaccination: A meta-analysis.  LINK

Vaccines and Stress Studies

(This is an overview of Stress interaction with immune that goes beyond the linear assumptions that the only side effects can be “local redness, pain and heat”)

How Stress influence the immune response http://www.direct-ms.org/sites/default/files/Stress%20and%20immunity.pdf In response to a stressor, physiological changes are set into motion to help an individual cope with the stressor. However, chronic activation of these stress responses, which include the hypothalamic–pituitary –adrenal axis and the sympathetic–adrenal–medullary axis, results in chronic production of glucocorticoid hormones and catecholamines. Glucocorticoid receptors expressed on a variety of immune cells bind cortisol and interfere with the function of NF-kB, which regulates the activity of cytokine-producing immune cells. Adrenergic receptors bind epinephrine and norepinephrine and activate the cAMP response element binding protein, inducing the transcription of genes encoding for a variety of cytokines. The changes in gene expression mediated by glucocorticoid hormones and catecholamines can dysregulate immune function. There is now good evidence (in animal and human studies) that the magnitude of stress-associated immune dysregulation is large enough to have health implications.

Neural regulation of innate immunity: a coordinated nonspecific host response to pathogens  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1783839/

The vaccine impact and increasing their effectiveness is as an ongoing endeavor and evolving science. If some Autisms have stress regulation factors (even before birth) relating to pain and immune activation at core then I think it’s something that needs continued investigation in conjunction with the need to improve disease prevention by whatever means science discovers, and by this changing paradigm of science.

Stressor-Induced Alterations of Adaptive Immunity to Vaccination and Viral Pathogens http://www.ncbi.nlm.nih.gov/pubmed/21094924

Impact of parent-directed education on parental use of pain treatments during routine infant vaccinations: a cluster randomized trial. http://www.ncbi.nlm.nih.gov/pubmed/25599314

Synergistic effects of psychological and immune stressors on inflammatory cytokine and sickness responses in humans. http://www.ncbi.nlm.nih.gov/pubmed/18835437 Typhoid vaccine induced a significant rise in participants’ serum levels of interleukin-6 (IL-6) and this response was significantly larger in the stress versus rest conditions. Our findings suggest that, as seen in animals, psychological and immune stressors may act synergistically to promote inflammation and sickness behaviour in humans.

Psychological stress and antibody response to influenza vaccination: when is the critical period for stress, and how does it get inside the body? http://www.ncbi.nlm.nih.gov/pubmed/15039506

Perceived stress decreases vaccine response
http://www.bio-medicine.org/medicine-news/Perceived-stress-decreases-vaccine-
response-1668-1/

Optimizing Benefits of Influenza Virus Vaccination during Pregnancy: Potential Behavioral Risk Factors and Interventions http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4043397/

Psychological Stress and Antibody Response to Immunization: A Critical Review of
the Human Literature http://www.psy.cmu.edu/~scohen/cohmillrab01.pdf Conclusions:
The literature supports a relationship between psychological stress and antibody responses to immunizations. The data are convincing in the case of secondary response but weak for primary response. More attention to the kinetics of stress and antibody response and their interrelations is needed in future research

Cortisol circadian rhythms and stress responses in infants at risk of allergic disease. http://www.ncbi.nlm.nih.gov/pubmed/16461131

Neonatal pain-related stress and NFKBIA genotype are associated with altered cortisol levels in preterm boys at school age http://www.ncbi.nlm.nih.gov/pubmed/24066085

Glucocorticoid exposure in preterm babies predicts saliva cortisol response to immunization at 4 months. http://www.ncbi.nlm.nih.gov/pubmed/16306199
Preterm babies are exposed to multiple stressors and this may have long-term effects. In particular, high levels of endogenous cortisol might have a programming effect on the hypothalamic-pituitary-adrenal axis as may administered glucocorticoids.

Cortisol and cardiovascular reactions to mental stress and antibody status following hepatitis B vaccination: a preliminary study http://www.ncbi.nlm.nih.gov/pubmed/12212655 In sum, variations in indices of both hypothalamic pituitary adrenocortical axis and sympathetic nervous system activity were associated with individual differences in immune response to vaccination.

New Evidence Explains Poor Infant Immune Response to Certain Vaccines, says MU Researcher April 1, 2009 http://munews.missouri.edu/news-releases/2009/0401-Zaghouani-Vaccines.php When Zaghouani gave the newborn mice an antigen shortly after birth, he noticed the presence of both Th-1 and Th-2 cells. However, when he gave the antigen a second time, he noticed an abundance of Th-2 cells that responded to the antigen instead of Th-1 cells.

Does an acute inflammatory response temporarily attenuate parasympathetic reactivation? http://www.ncbi.nlm.nih.gov/pubmed/20437076

Neonatal pain and developmental outcomes in children born preterm: a systematic review. http://www.ncbi.nlm.nih.gov/pubmed/24866853

Cortisol, behavior, and heart rate reactivity to immunization pain at 4 months corrected age in infants born very preterm. Grunau RE, Tu MT, Whitfield MF, Oberlander TF, Weinberg J, Yu W, Thiessen P, Gosse G, Scheifele D.Clin J Pain. 2010 Oct;26(8):698-704. Importantly, however, stress regulation seems altered in preterm male infants. As cortisol impacts development and functioning of the brain, altered stress regulation has important implications beyond pain systems.

Cortisol levels in former preterm children at school age are predicted by neonatal procedural pain-related stress. http://www.ncbi.nlm.nih.gov/pubmed/25313535

Impact of repeated procedural pain-related stress in infants born very preterm. http://www.ncbi.nlm.nih.gov/pubmed/24500615

Psychoneuroimmunology: Stress and Immunity http://tinyurl.com/7rll4xa

Chronic stress alters the immune response to influenza virus vaccine in older adults http://www.ncbi.nlm.nih.gov/pmc/articles/PMC39758/pdf/pnas01514-0427.pdf)

Tetanus toxoid stimulation of the hypothalamic-pituitary-adrenal axis correlates inversely with the increase in tetanus toxoid antibody titers. http://www.ncbi.nlm.nih.gov/pubmed/9589678

The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181830/

Sleep after vaccination boosts immunological memory.
Lange T, Dimitrov S, Bollinger T, Diekelmann S, Born J. J Immunol. 2011 Jul 1;187(1):283-90. Epub 2011 Jun 1.
http://www.ncbi.nlm.nih.gov/pubmed/21632713
The proinflammatory milieu induced during this sleep stage apparently acts as adjuvant that facilitates the transfer of antigenic information from APCs to Ag-specific Th cells. Like the nervous system, the immune system takes advantage of the offline conditions during sleep to foster adaptive immune responses resulting in improved immunological memory.

Morning vaccination enhances antibody response over afternoon vaccination: A cluster-randomised trial .Long JE, Drayson MT, Taylor AE, et al. Vaccine. 2016; doi:10.1016/j.vaccine.2016.04.032

Preliminary evidence that morning vaccination is associated with an enhanced antibody response in men. Phillips et al. Psychophysiology, 2008; 45 (4): 663 DOI: 10.1111/j.1469-8986.2008.00662.x

Vaccine-induced antibody responses as parameters of the influence of endogenous and environmental factors. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240401/

Vaccination responses may be influenced by a variety of factors other than environmental ones. One factor is the vaccine itself; a second is the vaccination procedure used. In addition, the intrinsic capacity of the recipient to respond to a vaccine, which is determined by sex, genetic factors, and age, is important. Psychological stress, nutrition, and (infectious) diseases are also likely to have an impact. We reviewed the literature on vaccine response. With regard to exogenous factors, there is good evidence that smoking, diet, psychological stress, and certain infectious diseases affect vaccination titers, although it is difficult to determine to what extent. Genetic factors render certain individuals nonresponsive to vaccination.

As a conceptual framework, we must “kill all pathogens” as a general way of approaching health is problematic in itself. It’s the very old and classic argument of “germ or terrain” whereas one approach (germ theory) approaches every pathogen as something to be destroyed, the more ecosystem-oriented terrain approach brings to the discussion the state of the system impacting the deadliness of the pathogen itself and/or proliferation of that pathogen. Also, there are what we might consider “pathogens”, or viruses, that play a considerable role in our evolution and that this knowledge, and changing approaches, may help us develop better vaccinations and programs from a more integrated systems perspective.

Microbiotia impact on nutrition (both food producing microbiota and the microbiota itself making and processing that nutrition making it available). The more we “clean” and sterilize our foods (and an antibiotics fix for all that ails us) brings into question if the more we impact these balances, do we impact our ability to handle stress.

Microbiome

Human nutrition, the gut microbiome and the immune system http://www.nature.com/nature/journal/v474/n7351/full/nature10213.html

I was curious about the claim that there is no scientific evidence-based research that an immature immune system can be bombarded (overwhelmed or become over-reactive). And I can see when we approach it from a perspective of antibody responses we could say “they have plenty” but the question remains what else happens in that antibody response? what else is needed, what else might be programmed? Are there better ways or other factors to consider? When we alter our assumptions of science and look at some facts of physiology and change those assumptions based on new science, we might start looking at this from a more systems perspective of the combination of factors and multiple impacts and layers that vaccines can have on multiple systems of an individual.

Unexpected partnership drives immunity 12 April 2012 http://www.domain-b.com/technology/Health_Medicine/20120412_unexpected_partnership.html New research challenges a well-established theory about antiviral immunity and may lead to a new understanding of the best way to help protect those exposed to potentially lethal viruses, such as rabies. The findings contradict the current view that the production of antibodies, a part of what is called adaptive immunity, are absolutely required to fight off certain types of viral infection.

I

Regulatory T cells play an important role in the establishment of immunological self-tolerance, thereby preventing autoimmunity…. contribute to autoimmunity in a subgroup of children with autism. Stress System Activity, Innate and T Helper Cytokines, and Susceptibility to Immune-Related Diseases http://instructional1.calstatela.edu/eporter/BIOL520/Literature/Calcagni%20et%20al%202006.pdf

Innate Cells and T Helper 2 Cell Immunity in Airway Inflammation http://www.cell.com/immunity/abstract/S1074-7613(09)00372-0

Activated mast cells, eosinophils, and basophils infiltrate the airways of asthmatics as a result of an overexuberant T helper 2 (Th2) cell immune response Frequency of CD4+CD25 high Regulatory T Cells in the Peripheral Blood of Egyptian Children With Autism http://jcn.sagepub.com/content/25/3/328.abstract

 

Gut Microbiota in Health and Disease doi: 10.1152/physrev.00045.2009 http://physrev.physiology.org/content/90/3/859.full

Here would be another interesting angle to explore, which would be the lowered or altered fats creating altered immune responses (still would have to act on a system and still has major combination of impacts, aka lowered nutritional status and multiple stressors acting on the system).  This example is through the Interluekin-10 regulation, which in this study infant formula with AA/DHA helped in the upregulation of IL-10 which could possibly happen after vaccination (Bassagany-Riera 2007)—- or many different/other kinds of stressors, like psychosocial (Bartolomucci 2003)—- and Autism is associated with lower regulation of IL-10. But again, MANY factors involved, clearly not a simple fix or causal pathway, but CONCEPTUALLY a different approach than Germ Theory Model of find something and take it away.

Arachidonic acid-and docosahexaenoic acid-enriched formulas modulate antigen-specific T cell responses to influenza virus in neonatal piglets. Bassaganya-Riera J, Guri AJ, Noble AM,Am J Clin Nutr. 2007 Mar;85(3):824-36. http://www.ncbi.nlm.nih.gov/pubmed/17344506 . ..immunomodulatory effects of AA/DHA-enriched formulas were consistent with up-regulation of interleukin 10 in peripheral blood mononuclear cells. CONCLUSION: Overall, it appears that the AA/DHA-enriched formula modulated antigen-specific T cell responses in part through an interleukin 10-dependent mechanism.

 

The optimal timing of the first MMR vaccine dose depends on 2 main factors. First, the infant’s immune system should be sufficiently mature to respond to the vaccine antigens. Second, levels of maternal antibodies must be low enough to ensure that they do not neutralize the live, attenuated strains in the vaccine. Insight in the kinetics and determinants of maternal antibody concentrations is therefore very important

Response of viral specific CD4 T cells to in vitro stimulation with vaccine and wild measles virus strains in vaccinated and naturally infected subjects.http://www.ncbi.nlm.nih.gov/pubmed/25115114

Differential Immune Responses to Primary Measles-Mumps-Rubella Vaccination in Israeli Children http://www.ncbi.nlm.nih.gov/pmc/articles/PMC515267/

Measles virus-induced suppression of immune responses http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2908915/

Age-dependent dysregulation of innate immunity. http://www.ncbi.nlm.nih.gov/pubmed/24157572

Pattern recognition receptors: sentinels in innate immunity and targets of new vaccine adjuvants. http://www.ncbi.nlm.nih.gov/pubmed/22309671

Stressor-induced alterations of adaptive immunity to vaccination and viral pathogens.http://www.ncbi.nlm.nih.gov/pubmed/21094924

Vaccine-Induced Antibody Responses as Parameters of the Influence of
Endogenous and Environmental Factors http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240401/pdf/ehp0109-000757.pdf

Environmental enrichment alters splenic immune cell composition and enhances secondary influenza vaccine responses in mice.http://www.ncbi.nlm.nih.gov/pubmed/24687160

The Impact of Obesity on Immune Response to Infection and Vaccine: An Insight into Plausible Mechanisms http://omicsonline.org/the-impact-of-obesity-on-immune-response-to-infection-and-vaccine-an-insight-into-plausible-mechanisms-2161-1017.1000113.php?aid=18763

Microbiome/Probiotics

Gut bacteria play key role in vaccination

http://www.sciencedaily.com/releases/2014/09/140911125813.htm

Probiotics and the immunological response to infant vaccinations: a prospective, placebo controlled pilot study. Youngster I, Kozer E, Lazarovitch Z, Broide E, Goldman M.Arch Dis Child. 2011 Apr;96(4):345-9. Epub 2011 Jan 24. http://www.ncbi.nlm.nih.gov/pubmed/21266337

Should the Human Microbiome Be Considered When Developing Vaccines? http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1001190

A viral understudy for commensal bacteria.

http://www.nature.com/nri/journal/v15/n1/full/nri3788.html

Differential Response of the Cynomolgus Macaque Gut Microbiota to Shigella Infection. PLoS ONE, 2013; 8 (6): e64212 DOI: 10.1371/journal.pone.0064212

Impact of Oral Typhoid Vaccination on the Human Gut Microbiota and Correlations with S. Typhi-Specific Immunological Responses. PLoS ONE, 2013; 8 (4): e62026 DOI: 10.1371/journal.pone.0062026

Intestinal bacteria needed for strong flu vaccine responses in mice http://www.sciencedaily.com/releases/2014/09/140911125813.htm

TLR5-Mediated Sensing of Gut Microbiota Is Necessary for Antibody Responses to Seasonal Influenza Vaccination. Immunity, 2014; DOI: 10.1016/j.immuni.2014.08.009

Stool Microbiota and Vaccine Responses of Infants http://pediatrics.aappublications.org/content/134/2/e362.abstract

Genetic Variation

Associations between Single Nucleotide Polymorphisms in Cellular Viral Receptors and Attachment Factor-Related Genes and Humoral Immunity to Rubella Vaccination http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0099997

The genetic regulation of infant immune responses to vaccination http://journal.frontiersin.org/article/10.3389/fimmu.2015.00018/full

A number of factors are recognized to influence immune responses to vaccinations including age, gender, the dose, and quality of the antigen used, the number of doses given, the route of administration, and the nutritional status of the recipient. Additionally, several immunogenetic studies have identified associations between polymorphisms in genes encoding immune response proteins, both innate and adaptive, and variation in responses to vaccines. Variants in the genes encoding Toll-like receptors, HLA molecules, cytokines, and cytokine receptors have associated with heterogeneity of responses to a wide range of vaccines including measles, hepatitis B, influenza A, BCG, Haemophilus influenzae type b, and certain Neisseria meningitidis serotypes, amongst others. However, the vast majority of these studies have been conducted in older children and adults and there are very few data available from studies conducted in infants. This paper reviews the evidence to date that host genes influencing vaccines responses in these older population and identifies a large gap in our understanding of the genetic regulation of responses in early life. Given the high mortality from infection in early life and the challenges of developing vaccines that generate effective immune responses in the context of the developing immune system further research on infant populations is required.

Variability in Immune Response to Pathogens: Using Measles Vaccine to Probe Immunogenetic Determinants of Response (HLA Genes) http://www.sciencedirect.com/science/article/pii/S0002929707634843

HLA Immune Function Genes in Autism. http://www.hindawi.com/journals/aurt/2012/959073/

Differential genetic determination of immune responsiveness to hepatitis B surface antigen and to hepatitis A virus: a vaccination study in twins http://www.sciencedirect.com/science/article/pii/S014067360211083X

Associations between Measles Vaccine Immunity and Single-Nucleotide Polymorphisms in Cytokine and Cytokine Receptor Genes http://jid.oxfordjournals.org/content/195/1/21.long

The genetic basis for interindividual immune response variation to measles vaccine: new understanding and new vaccine approaches(2013) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570049/

Integrative genomic analysis of the human immune response to influenza vaccination http://elifesciences.org/content/2/e00299

Genome-wide SNP associations with rubella-specific cytokine responses in measles-mumps-rubella vaccine recipients. http://www.ncbi.nlm.nih.gov/pubmed/24811271/

Global analyses of human immune variation reveal baseline predictors of postvaccination responses. http://www.ncbi.nlm.nih.gov/pubmed/24725414

Parental caregivers of children with developmental disabilities mount a poor antibody response to pneumococcal vaccination. http://www.ncbi.nlm.nih.gov/pubmed/18595654

Modification of neurobehavioral effects of mercury by a genetic polymorphism of coproporphyrinogen oxidase in children. http://www.ncbi.nlm.nih.gov/pubmed/22765978

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