Mass Vaccination against Swine Flu H1N1 in the US

a few abstracts:

from those 4,000+ articles

Requirement of dying cells and environmental adjuvants for the induction of autoimmunity.

OBJECTIVE: Cells commonly die without eliciting autoimmunity. However, dying cells are a potential initiating stimulus for systemic lupus erythematosus (SLE). Our goal was to verify whether immune adjuvants influence the autoimmunity induction that ensues following in vivo injection of dying cells. METHODS: Mice were immunized with apoptotic thymocytes in the presence of artificial moieties, such as Freund's incomplete adjuvant (IFA), or natural adjuvants, such as dendritic cells (DCs). Renal involvement and the development of autoantibodies were monitored. RESULTS: Apoptotic cells failed to induce clinical disease or to sustain production of autoantibodies in (NZB x NZW)F(1) mice. In contrast, autoimmunity developed in the presence of IFA or DCs. The characteristics of the adjuvant influenced the array of autoantibodies, the kinetics of their development, and the severity of the disease. DCs were required for induction of anti-beta(2)-glycoprotein I IgG. Adjuvants alone did not elicit disease. CONCLUSION: A "two-hit" signal composed of autoantigens and adjuvants initiates systemic autoimmunity. Moreover, environmental signals at the site of clearance of dead cells shape the features and the severity of the autoimmune disease. Strategies aimed at preventing the accumulation of dying cells and at modulating endogenous adjuvants may be beneficial for the treatment of SLE.

Autoimmunity induced by adjuvant hydrocarbon oil components of vaccine.

Adjuvant oils such as Bayol F (Incomplete Freund's adjuvant: IFA) and squalene (MF59) have been used in human and veterinary vaccines despite poor understanding of their mechanisms of action. Several reports suggest an association of vaccination and various autoimmune diseases, however, few were confirmed epidemiologically and the risk of vaccination for autoimmune diseases has been considered minimal. Microbial components, not the adjuvant components, are considered to be of primary importance for adverse effects of vaccines. We have reported that a single intraperitoneal injection of the adjuvant oils pristane, IFA or squalene induces lupus-related autoantibodies to nRNP/Sm and Su in nonautoimmune BALB/c mice. Induction of these autoantibodies appeared to be associated with the hydrocarbon's ability to induce IL-12, IL-6, and TNF-alpha, suggesting a relationship with hydrocarbon's adjuvanticity. Whether this is relevant in human vaccination is a difficult issue due to the complex effects of vaccines and the fact that immunotoxicological effects vary depending on species, route, dose, and duration of administration. Nevertheless, the potential of adjuvant hydrocarbon oils to induce autoimmunity has implications in the use of oil adjuvants in human and veterinary vaccines as well as basic research.

Environmental adjuvants, apoptosis and the censorship over autoimmunity.

Alterations during apoptosis lead to the activation of autoreactive T cells and the production of autoantibodies. This article discusses the pathogenic potential of cells dying in vivo, dissecting the role of signals that favor immune responses (adjuvants) and the influence of genetic backgrounds. Diverse factors determine whether apoptosis leads or not to a self-sustaining, clinically apparent autoimmune disease. The in vivo accumulation of uncleared dying cells per se is not sufficient to cause disease. However, dying cells are antigenic and their complementation with immune adjuvants causes lethal diseases in predisposed lupus-prone animals. At least some adjuvant signals directly target the function and the activation state of antigen presenting cells. Several laboratories are aggressively pursuing the molecular identification of endogenous adjuvants. Sodium monourate and the high mobility group B1 protein (HMGB1) are, among those identified so far, well known to rheumatologists. However, even the complementation of apoptotic cells with potent adjuvant signals fail to cause clinical autoimmunity in most strains: autoantibodies generated are transient, do not undergo to epitope/spreading and do not cause disease. Novel tools for drug development will derive from the molecular identification of the constraints that prevent autoimmunity in normal subjects.

NB.  External triggers of autoimmunity does not necessarily lead to disease in normal subjects; genetic predisposition is important.

Acquired autoimmunity after viral vaccination is caused by molecular mimicry and antigen complimentarity in the presence of an immunologic adjuvant and specific HLA patterns.

Acquired autoimmunity syndromes occur after viral vaccinations. Molecular mimicry is involved in these phenomena as is the necessity for the presence of two chemically complimentary antigens and an immunologic adjuvant. The HLA pattern of the host is also an important factor. The example used to explain these phenomena is demyelinating disease that follows hepatitis B vaccination. The somatic antigen of the hepatitis B virus in the vaccine has chemical complimentarity with the Epstein-Barr virus antigen in the vaccine recipient. The Epstein-Barr virus shows molecular mimicry with human myelin. The immunologic adjuvant is either present in the vaccine or muramyl peptides in the individual who is vaccinated. Why more than one type of autoimmune disease occurs is explained by the fact that specific autoimmune T-cells have been shown to develop clones that attack multiple human tissues.

All 'safety concerns' are hypothetical.  If not, they'd be called side effects...

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by: SusanC @ Fri Aug 07, 2009 at 03:28:15 AM CDT

Feels good to know that

you are working as hard as you obviously are on this matter.

In a matter like this pandemic, do the U.S. government and/or MSM ever intentionally deceive us?  

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by: ssal @ Fri Aug 07, 2009 at 06:05:01 AM CDT

I am, working as hard as I can

but everyone will also do their bit, each in their own way..


All 'safety concerns' are hypothetical.  If not, they'd be called side effects...

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by: SusanC @ Fri Aug 07, 2009 at 11:36:25 AM CDT

[ Parent ]

To avoid possible misinterpretation,

I probably should have said "the matter of adjuvants" instead of "this matter."

I get the feeling it is likely no one else may be looking into concerns about adjuvants as thoroughly as you are.  

In a matter like this pandemic, do the U.S. government and/or MSM ever intentionally deceive us?  

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by: ssal @ Sat Aug 08, 2009 at 06:03:40 AM CDT

[ Parent ]

it got more and more interesting ;-)

I get the feeling it is likely no one else may be looking into concerns about adjuvants as thoroughly as you are.  

and, the science is scattered, but growing exponentially, so it takes a lot of sleuthing to figure things out.


All 'safety concerns' are hypothetical.  If not, they'd be called side effects...

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by: SusanC @ Sat Aug 08, 2009 at 06:17:01 AM CDT

[ Parent ]

If the fall wave kills more people, the decisions about adjuvants might be easier to make.

If the lethality stays the same, with 70% of fatal cases happening in those with underlying conditions, then it's like a roll of the dice either way, will you or your kids be in the unlucky 30% who die with no underlying conditions or be in the small(?) group with hidden vulnerability re. autoimmune disease.  

OTOH, in a fall wave the death rate may rise even without an increase in lethality of the virus itself, because more will be ill at the same time, and the hospitals will be even more overwhelmed than they are now, and the seriously ill won't be able to get proper treatment.  

My daughter is grown, but if she were younger, I would do anything I could manage to avoid an adjuvanted vaccine.  I'd keep her out of school and try to avoid infection until there was an unadjuvanted vaccine available.  In a severe flu, it wouldn't be necessary for us to mix with others; we could be patient.  Others may be in different circumstances.  

The policy on vaccines should take into account the different situations that people have, and consider another layer of priorities for vaccination: those who must go to work (and their families, or make dormitories for workers so they don't infect their families), and those who can withdraw from society for a time until enough good (unadjuvanted) vaccine is available.  

It would lessen the necessity for an adjuvanted vaccine if there were a way of volunteering to wait, to put onesself at the end of the line, in order to protect those who should be vaccinated first.  It's elitist in a way to know that one mother can put her children's welfare ahead of everything else because she isn't living paycheck to paycheck.  We should be realistic enough to recognize this reality and help every mother put her children first, by not putting adjuvant in the vaccine and stretching the supply by lessening the demand.

"The truth does not change according to our ability to stomach it."  Flannery O'Connor

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by: Jane @ Fri Aug 07, 2009 at 10:54:40 AM CDT

the odds are not 30%

If the lethality stays the same, with 70% of fatal cases happening in those with underlying conditions, then it's like a roll of the dice either way, will you or your kids be in the unlucky 30% who die with no underlying conditions or be in the small(?) group with hidden vulnerability re. autoimmune disease.  

in case someone misreads this.  The odds of anyone getting infected (according to these planning assumptions) is 30%.  Of those 30%, the CFR is about 0.1-0.3%.  Let's assume the higher.  So the odds of anyone, with or without any prior medical conditions, dying from the fall wave is 0.09%.  This risk, of 0.09%, applies to you only if you assume the risk is the same whether one is healthy or not.  

Obviously that assumption is not correct, since we do not have 70% of the general population having such conditions. We don't know what is the percentage of people with such conditions in the population - the ACIP figures gave 34M in those aged 25-64 plus 5M in ages 5-18.  Obviously this 39M does not cover all age groups, but even so it's a LONG way from 210M (70% of 300M).

OTOH, all of the above is assuming the characteristics of the most susceptible population does not change.  Right now there are very few infections in the elderly but they have very high CFR.  It's hard to tell whether this is truly due to low attack rate (which means a truly high CFR) or due to most cases in the elderly being missed (which would imply a lower CFR).  If, as happened in 1957, older people are spared initially only because the virus first spreads among the young and then affect the elderly later, then we will see more older people getting infected and dying from it as time goes on.  

If this happens slowly, say after 4-5 months, we would be nearing the time when there's enough vaccine for the whole population (February 2010). If this happens quickly, eg in October, there will not be enough vaccines to cover this age group.  In which case, there may IMO be a case for considering using adjuvanted vaccines for the elderly, since they are more likely to benefit from a stronger immune response and less likely to have autoimmune or other adverse events from such vaccines (see 'safety signal with MF59, in top diary)


All 'safety concerns' are hypothetical.  If not, they'd be called side effects...

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by: SusanC @ Fri Aug 07, 2009 at 12:08:10 PM CDT

[ Parent ]

Thanks for clarifying my numbers!

As a mom, I'm kind of pessimistic, so I was only looking at the deaths instead of chances of death.  Somebody's kids were in that 30%, so why should I think we're safe? [rhetorical question]  Being lucky isn't something I'm willing to count on; besides, DD has a kind of autoimmune disease already, even though she is "healthy".  That disease didn't show up until she was about 20 and got sick in a foreign country, was treated too late, and possibly incorrectly.

"The truth does not change according to our ability to stomach it."  Flannery O'Connor

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by: Jane @ Fri Aug 07, 2009 at 12:45:16 PM CDT

[ Parent ]

Underlying Conditions

Assuming the list of underlying conditions is massive ... what would be the definition of a person without underlying conditions?  Are we talking the perfect specimen or just the regular healthy individual?

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by: Rural Dweller @ Fri Oct 16, 2009 at 21:33:58 PM CDT

[ Parent ]

underlying conditions - research

That's an extremely important question.

I've read relative risk for pregnant women is about 4-5.  (Somewhere in an ECDC report, maybe a couple of weeks ago.)

Thing is, pregnancy is an "all or nothing" condition, and relatively easy to assess, specially towards the end.

Overweight has degrees and can be assessed if standardised, and if data are collected.

Most if not all other conditions are harder, but not impossible, to define operationally: heavy smoking, asthma of different aerosol intakes or whatever.

I'm afraid different data is collected in different levels, AFAIK.  We know if severe patients are pregnant.  But do we know if "mild" (by whatever criteria) are pregnant?

I'm guessing this needs its own diary, called "hard data about relative risk for severe flu".  Ah, here it is: http://newfluwiki2.com/diary/4...

You arm yourself to the teeth just in case.  You don't leave the gun near the baby's hand.

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by: lugon @ Sat Oct 17, 2009 at 02:55:48 AM CDT

[ Parent ]

determining priority groups

The policy on vaccines should take into account the different situations that people have, and consider another layer of priorities for vaccination: those who must go to work (and their families, or make dormitories for workers so they don't infect their families), and those who can withdraw from society for a time until enough good (unadjuvanted) vaccine is available.  

is difficult.  There are many issues to consider, including logistical ones eg whether such groups are easily identifiable (or verifiable) - it affects the ability to deliver simple messages to the public.  The severity of a pandemic is another.  In a high CFR scenario like an H5N1 pandemic, the group of 'essential workers' needed to keep society going, would include more than the frontline HCWs and emergency medical people, as per the previous prioritization recommendations made for an H5N1 scenario.  

But with this H1N1, the risk of a healthy working person dying from this pandemic is so low, that it would be more important to use vaccines to reduce infection risk for the young and for those vulnerable to complications instead.  


All 'safety concerns' are hypothetical.  If not, they'd be called side effects...

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by: SusanC @ Fri Aug 07, 2009 at 12:20:34 PM CDT

[ Parent ]

True, but if there isn't enough vaccine to cover these groups,

I don't want them to add adjuvants to stretch it.  I would like them to promise that they won't add it, except for the elderly.  

"The truth does not change according to our ability to stomach it."  Flannery O'Connor

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by: Jane @ Fri Aug 07, 2009 at 12:51:19 PM CDT

[ Parent ]

someone has to get up and say it!!

if that's how you feel.  Turn up in one of those public engagement meetings and SAY it, if you can...


All 'safety concerns' are hypothetical.  If not, they'd be called side effects...

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by: SusanC @ Fri Aug 07, 2009 at 13:00:32 PM CDT

[ Parent ]

"elderly" is ____ ?

I'm not sure if I'm "elderly."

(but there's little doubt I can be justifiably referred to as an "old __")

In a matter like this pandemic, do the U.S. government and/or MSM ever intentionally deceive us?  

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by: ssal @ Sat Aug 08, 2009 at 05:51:53 AM CDT

[ Parent ]

65 or over, LOL

following ACIP recommendations.


All 'safety concerns' are hypothetical.  If not, they'd be called side effects...

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by: SusanC @ Sat Aug 08, 2009 at 06:15:16 AM CDT

[ Parent ]

Vaccine for the Young - Especially If Schools Remain Open

Looks like the tide is turning away from school closings as community mitigation.

Hope the vaccines can beat this pandemic to the school-house door.

The 'or else' won't be pretty.  

ITW(Joel J)
Courage is resistance to fear, mastery of fear - not absence of fear.
- Mark Twain
 

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by: Into The Woods @ Fri Aug 07, 2009 at 15:08:09 PM CDT

[ Parent ]

if they have plenty of LAIV

tested safe etc, and if they can just use them with droppers, it will be so much easier to vaccinate a lot of kids, than with injections.


All 'safety concerns' are hypothetical.  If not, they'd be called side effects...

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by: SusanC @ Fri Aug 07, 2009 at 15:15:24 PM CDT

[ Parent ]

Lots of Ifs to Assume

While creating the sense that school closing is no longer really on the menu, there are still a lot of 'ifs' to contend with.

If they are forced to change direction again and recommend school closing they have created a lot of confusion that will lead to delay and non-compliance.

The waters have already been muddied on an issue where state and local decision-makers need solid best-practices support to make timely decisions and fend off all those that will oppose school closings.  

ITW(Joel J)
Courage is resistance to fear, mastery of fear - not absence of fear.
- Mark Twain
 

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by: Into The Woods @ Fri Aug 07, 2009 at 15:20:23 PM CDT

[ Parent ]

I don't think the case is closed

about whether or not to close schools.  That's just the CDC (specifically Frieden's) preference; or at least that's what it looks like to me.  There may be good public health grounds for that, but I think they are seriously underestimating the parents' POV.  Notice there has been NO attempt in public engagement on the school closure issue.  If this virus spreads as rapidly as the models predict (which btw revere has a good angle on it here), public attention and opinion can turn very quickly.  

Right now I'm neutral on whether schools should close, you can argue it both ways, and I can see about equal pros and cons either way.  But I'm not a representative opinion, and parents do not care about the public health implications, just the safety of their kids.  

Whichever way they go, tptb have their job cut out for them, for explaining what they think is the right thing to do, and why, to the public..


All 'safety concerns' are hypothetical.  If not, they'd be called side effects...

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by: SusanC @ Fri Aug 07, 2009 at 15:39:22 PM CDT

[ Parent ]

I agree on parents' POVs

There were about 700 schools that closed this spring -- that didn't happen because of gov't recommendations (I don't think) so much as schools reacting to parental reaction to sudden increase in illness. If the school absentism reaches 30-40% due to illness, don't you think they'll close for a week or so? Of course, it's too late to mitigate the spread then, but I think we will see a lot of closings, if the flu spreads as fast as it has in the Southern Hemisphere. Even if it's just a "rotten flu" rather than a case for hospitalization...  

Keep the information coming!

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by: Cathy M @ Fri Aug 07, 2009 at 16:03:33 PM CDT

[ Parent ]

School Closure Was Part of Status Quo Response Plan

School closure caused by the flu appears to be very likely if current guidance is followed.  Depending on the circumstances, that might be fine or we might be paying the price without getting any benefit we otherwise might get if closure was preventative as was done in the spring.

At this point I am less concerned with what the final policy should be and more concerned with assuming that the lower standard they are discussing should be the new normal.  It is always more difficult to move people up to a higher state of readiness than it is to let them down a notch or two.  With the existing levels of uncertainty, I don't see the advantage in ramping down now, as opposed to closer to to the event.

Based on the guidance and response plans in place when 2009 H1N1 started spreading this spring, there was at least a modicum of clarity and consistency on the part of the response plan that assumed that early closure of the schools was recommended. ("Early" for H1N1 being when a student or staff had or was suspected of H1N1 - not the higher standard of "early" envisioned for H5N1 that would have potentially been "any H5N1 in your area".)

It was already dropping down the ladder a few rungs from the 'plan' which made it more saleable to the public.

So when state and local decision makers ordered (or advised) such early closure they were solidly in the mainstream.  

Now the ground is shifting underneath their feet.  If the final effective recommendation is what they just announced, it may work ok - again, the lower standard will be easier to use.

I'm just concerned that lowering the standard now may make it more difficult in the future if anyone, even on a local basis, decides that their standard has to go back up (schools close earlier - longer).

The lower standard seems based on assumptions that a) H1N1 is not going to be more virulent (or siginficantly more disruptive) in its second wave than it was last spring, b) Sufficient vaccine will be available and c) There is no other reason that school closure would be adviseable (e.g. a need emerges to lower and delay the surge to take pressure off an unexpectedly overtopped health care system and/or buy time for unexpectedly delayed vaccines).  If these assumptions turn out to be wrong, ramping public and school system expectations back up to a readiness and willingness to deal with early closure has been tossed a couple new challenges.

Challenge # 1:  In the meantime, schools will slack off on planning/preparing for closure. (Already low on money and resources, if it's not a priority, they won't be getting ready for it and neither will parents.)

Challenge # 2:  It makes it more difficult to get public support and compliance if, in the end, pre-emptive school closing becomes adviseable because such a JIT message of higher/quicker response will be percieved as fickle, over-reactive and unjustified by the science and expert opinion.

You are undoubtedly correct that parents may vote with their feet (or their childrens' feet), and that may impact individual situations, but for most not until it is too late to buy any good from it - potentionally even for their own children who may have already been exposed.  

ITW(Joel J)
Courage is resistance to fear, mastery of fear - not absence of fear.
- Mark Twain
 

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by: Into The Woods @ Fri Aug 07, 2009 at 17:28:20 PM CDT

[ Parent ]

"Dormitories for workers"

Or perhaps some sort of portable "microrooms" (tiny campers) in which individual workers can live physically separate from but close to their families?

In a matter like this pandemic, do the U.S. government and/or MSM ever intentionally deceive us?  

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by: ssal @ Sat Aug 08, 2009 at 06:12:08 AM CDT

[ Parent ]

adjuvant analogy

adjuvants are substances added to vaccines to boost the immune response

I've been reading and learning a bit aboud adjuvants for a while, but my background in science is not great.

I am realizing I need an analogy to help me understand what an adjuvant is and how it works.

When I originally read the explanation for adjuvant, above, that it "boosts the immune system", I thought that an adjuvant is something that you add to the vaccine, to make the vaccine work better.

Kind of like how, when you are baking bread, you might add a little sugar to the yeast, to make sure the yeast will make the breat rise.

But the more I think about it, the adjuvant is being added to the vaccine, to make your BODY work differently.

It doesn't have an effect on the vaccine components.  It is being added, to change something in your body.  It makes your immune system work ... harder?

Is this a temporary change to the immune system, or is it a permanent change?   Is it something like the Energizer Bunny -- does the effect of the adjuvant on the immune system just keep going... and going... and going?

Or does the adjuvant stop boosting the immune system and some point?

GetPandemicReady.org - non commerical website with practical ways for families to prepare.

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by: Average Concerned Mom @ Fri Aug 07, 2009 at 16:42:25 PM CDT

Adjuvants: try this analogy

The adjuvant stands next to the antigen, waving a red flag and shouting to the immune system "Hey look, over here, come quick, all of you!". The idea is that the effect is temporary - it gets the immune system excited enough that the "memory" of this antigen is strong, even if there was only a tiny amount of antigen, and then the adjuvant is cleared from the body, leaving that strong immune memory as the only effect. It does seem reasonable to me to assume that squalene, the key ingredient in the adjuvants we're talking about, is cleared rather than sticking around, since it's a substance that's produced in the body anyway, so the body has mechanisms for clearing it. Unfortunately that's not enough to ensure that there won't be any permanent effect. The immune system is a complex system, and can sometimes, in some people, be "jolted" into a different state, e.g. an autoimmune disorder, by events that in other people would have no long-term effect. The $64k question is whether anything like that can happen as a result of receiving an adjuvanted vaccine, and if so, how badly and how often.

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by: Mathematician @ Fri Aug 07, 2009 at 16:53:39 PM CDT

[ Parent ]

Maybe instead of a red flag being waved for attention, it's a gun on auto-fire?

The gun can be removed but the damage has been done.

 ...Because of excessive reactogenicity and/or toxicity, the current version of MF59 used in an adjuvanted influenza vaccine (FLUAD) registered in Italy does not contain MTP but instead just squalene oil and surfactants.43,44 Published data suggests addition of MF59 only induces a modest (about 25%) increase in antibody levels in the elderly and no difference in younger individuals when compared to unadjuvanted influenza vaccine.4,45 Furthermore, there was little evidence that MF59 is antigen-sparing for influenza vaccines, since the same antigen dose is required for MF59 as for the unadjuvanted vaccine.4,45...

Limitations of MF59.  On the negative side, MF59, like all other oil-in-water adjuvants, is associated with major increases in injection site pain and reactogenicity.4 Another concern with squalene oil is its ability to induce chronic inflammatory arthritis in susceptible animal models.48 Susceptibility to squalene arthritis is genetically determined, raising the risk that adjuvants based on squalene oil may also induce or exacerbate inflammatory arthritis in genetically susceptible humans.48

http://biopharminternational.f...
At this point there is no test for genetic susceptibility, so it's a gamble.  :-/

How do you know the squalene is cleared, though?  The squalene in a vaccine is a mixture, injected into a muscle.  Would that make it harder to clear?  Here are the ingredients, but I don't know what these things are.

MF59 is a submicron oil-in-water emulsion which contains 4-5% w/v squalene, 0.5% w/v Tween 80, 0.5% Span 85, and optionally, varying amounts of muramyl tripeptide phosphatidyl-ethanolamine (MTP-PE), which activates non-TLR sensing receptors known as NOD-LRRs (reviewed in Akira42 )

"The truth does not change according to our ability to stomach it."  Flannery O'Connor

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by: Jane @ Fri Aug 07, 2009 at 17:36:56 PM CDT

[ Parent ]

Oops? We didn't mean to do that?

As any immunologist will tell you, the way an antigen encounters the immune system makes all the difference. You can eat squalene - no problem as it is an oil the body can easily digest. But studies in animals and humans show that injecting squalene will "galvanize the immune system into attacking it, which can produce a self-destructive cross reaction against the same molecule in the places where it occurs naturally in the body - and where it is critical to the health of the nervous system." (6)

http://rigorousintuition.ca/bo...
http://www.vaclib.org/basic/ad...

"The truth does not change according to our ability to stomach it."  Flannery O'Connor

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by: Jane @ Fri Aug 07, 2009 at 17:56:37 PM CDT

[ Parent ]

you're absolutely right

the adjuvant sticks around for only a short time, but the immune responses that it leaves behind can last a long time.  It the same as the immune memory that happens with the response to the vaccine antigen - you have the immune memory so that next time you encounter the same antigen, the virus, your body can mount a robust response.

The only difference is the encounter with the antigen, for the self-antigens in the body, is not 'next time' but, every time, every day.  And the antigen does not ever run out, so you have a chronic and excessive unstoppable response, causing disease.

Now, this doesn't happen to everyone, because our bodies have clever regulatory systems that can deal with such things.  But such systems are not perfect and can get overrun if you challenge them too strongly.  They do get overrun if you have certain types of genes that make some parts of the process more difficult to balance and regulate than in others without those genes.

The biggest practical problem that we have, is that we have no way of predicting accurately who would have problems with adjuvants. If you already have autoimmune disease, or someone in your family has it, chances are you may be more likely to have problems, but it's not a 100% relationship, cos you may not have the genes that your sibling has, for example.  The other problem is you may have the genes and no one in your family has it, or has had any problems, so you still can't tell.  Or the genes are expressed in a complex way and we don't as yet have a perfect understanding, enough to do any screening tests to find out who is or is not at risk!

WARNING: The less geeky reader can stop here and skip to the last 2 paragraphs of this comment!  LOL

There are now high throughput technology to screen the human genome to find which genes correlate to disease.  I will quote one of many that I found - several such studies have given some strong clues about a few genes for lupus, like the ITGAM

Hom 2008, Association of Systemic Lupus Erythematosus with C8orf13-BLK and ITGAM-ITGAX
Maier 2009,Autoimmunity risk alleles in costimulation pathways
Wang 2009, ITGAM is associated with disease susceptibility and renal nephritis of systemic lupus erythematosus in Hong Kong Chinese and Thai

This gene is one of 891 genes upregulated by MF59, in this paper Mosca 2008, Molecular and cellular signatures of human
vaccine adjuvants, which says

Itgam/CD11b, was up-regulated at high levels by MF59 already at 12 h (Fig. S2). We monitored the recruitment of CD11b+ cells by immunofluorescence analysis and found that at 1 day after injection, only MF59 induced influx of CD11b+ cells into the muscle (Fig. 3 Left). This finding is consistent with previous data obtained from muscle single-cell suspension, which showed that at 1 day after injection, MF59 induced a influx of mononuclear cells (16). All adjuvants induced the recruitment of CD11b+ cells with similar efficiency 4 days after injection

Now the CD11b+ pathway involves (from the paper by Wang et al)

The product of ITGAM, integrin-aM (CD11bþ), is a molecule that combines with integrin-b2 to form a leukocytespecific integrin. The aMb2-integrin is important in the adherence of neutrophils and monocytes to stimulated endothelium and in the phagocytosis of complement-coated particles. Ligation of the complement C3 activation product iC3b to integrin-aM on antigen-presenting cells results in the production of TGFb2 and IL10, a process that is essential for the induction of tolerance (12). Molad et al. (13) reported that neutrophils from SLE patients with more active disease expressed greater CD11b/CD18 than those from controls or patients with less active disease. In addition to clearance of immune complexes, ITGAM may suppress differentiation of helper T-cell type 17 (Th17), a pathway that has been shown to be involved in autoimmunity (14,15). ITGAM deficiency may also lead to enhanced IL6 production by antigen presenting cells, which subsequently promotes preferential differentiation of naive T cells to Th17 (16).

such an enhancement of IL6 was demonstrated very clearly by a study in 1994 from Chiron (before it became Novartis), Valensi 1994 Systemic Cytokine Profiles in BALB/c Mice Immunized with Trivalent Influenza Vaccine Containing MF59 Oil Emulsion and Other Advanced Adjuvants.

This is one example of rapidly emerging evidence from immunology showing us the overlapping points where disturbances in a normal/desirable immune response (enhancement of CD11b+ activity) that could play a role in making sure our body does not overshoot, becomes detrimental in patients with genetic defects in the same pathway.  

In a way, it's not all bad news.  Maybe some years or decades down the road, we will be able to tell with some precision who should or should not take such adjuvanted vaccines, but until that day arrives, everything that I've learned tells me we need to be very cautious with this kind of powerful stuff!


All 'safety concerns' are hypothetical.  If not, they'd be called side effects...

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by: SusanC @ Fri Aug 07, 2009 at 23:13:25 PM CDT

[ Parent ]

IL6 is also shown to be up-regulated

in the Mosca et al paper.  Here's a little diagram from that paper showing some (not all) of the genes regulated by 3 different adjuvants, MF59, alum, and CpG.

All 'safety concerns' are hypothetical.  If not, they'd be called side effects...

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by: SusanC @ Sat Aug 08, 2009 at 00:24:32 AM CDT

[ Parent ]

Maybe an adjuvant works like a tiny Borg on Star Trek

("You will be assimilated")because it changes you permanently.  The Energizer battery eventually loses its power.  There isn't any treatment for the changes made by the adjuvant though; it changes someone's body.  SusanC's post explained it better than I can (from her first post):

The following paragraph is taken from the immunology textbook Janeway's Immunobiology (page 615)

   14-11  Chronic autoimmune disease develops through positive feedback from inflammation, inability to clear the self antigen, and a broadening of the autoimmune response.

   When normal immune responses are engaged to destroy a pathogen, the typical outcome is the elimination of the foreign invader, after which the immune response ceases, leaving only an expanded cohort of memory lymphocytes.  In autoimmunity, however, the self antigen cannot easily be eliminated, because it is in vast excess or is ubiquitous, as with the SLE autoantigen, chromatin.  Thus, a very important mechanism for limiting the extent of an immune response cannot apply to autoimmune diseases.  Instead autoimmune diseases tend to evolve into a chronic state.  There is no cure for such diseases once they are well established - short of a bone marrow transplant that replaces much of the immune system from new cohorts of precursor cells.  Even this may not be successful in curing disease.

"The truth does not change according to our ability to stomach it."  Flannery O'Connor

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by: Jane @ Fri Aug 07, 2009 at 20:58:52 PM CDT

[ Parent ]

Suscan - do you ever sleep? Outstanding job as always nt

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by: LauraB @ Fri Aug 07, 2009 at 18:25:07 PM CDT

I just did, actually LOL

I worked on this for several days, not getting much sleep, and finally tonight my brain quit, and I went to bed at a scandalously early hour of 11pm!

Now I'm up at 4:30am. LOL.

Thanks for your kind comment.


All 'safety concerns' are hypothetical.  If not, they'd be called side effects...

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by: SusanC @ Fri Aug 07, 2009 at 22:33:54 PM CDT

[ Parent ]

thank you for getting all the info together!

I did print out your post for the Lincoln meeting, and also a number of the linked references -- shared it with my table - most were very appreciative to read some of the info -- hopefully we get some new members or at least lurkers from it..   Having read your posts and info for the past 2 years, I have to say I don't know how you get it all done.  I am in awe of you!  Thank you very much!!!

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by: elint6000 @ Sun Aug 09, 2009 at 11:27:19 AM CDT

[ Parent ]

thank you for helping to spread the word

see, we play different roles, which is what makes this community great!  ;-)


All 'safety concerns' are hypothetical.  If not, they'd be called side effects...

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by: SusanC @ Sun Aug 09, 2009 at 11:31:37 AM CDT

[ Parent ]

Great Work

Read it all and taking a copy as reference tomorrow.  Thank you very much for all your hard work SusanC.

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by: FluMom @ Sat Aug 08, 2009 at 01:38:42 AM CDT

good luck and keep us posted! n/t

All 'safety concerns' are hypothetical.  If not, they'd be called side effects...

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by: SusanC @ Sat Aug 08, 2009 at 01:48:49 AM CDT

[ Parent ]

Officials lower expectations for size of first novel flu vaccine deliveries

http://www.cidrap.umn.edu/cidr...

Aug 14, 2009 (CIDRAP News) - Federal officials today during a pandemic H1N1 planning update dialed back the number of novel flu vaccine doses they expect in October from 120 million to 45 million, listing several reasons for the smaller projection.

During a late July meeting of a federal immunization advisory panel, which targeted 159 million people to receive the first doses, authorities projected that 120 million doses would be available in October, with another 80 million per month in the following months.

However, during a National Biodefense Safety Board (NBSB) teleconference today, Dr. Robin Robinson, director of the Biological Advanced Research and Development Authority (BARDA) at the US Department of Health and Human Services (HHS), said the latest expectation is 45 million doses by mid October, with manufacturers delivering 20 million doses per week after that.

He said the revised estimate is based on several factors expected to slow vaccine delivery from manufacturers. Health officials have already acknowledged that yields of the novel H1N1 antigen are less than for the seasonal flu vaccine. Robinson also said vaccine makers have a limited number of fill-and-finish sites, which are just completing seasonal flu vaccine production, but that federal officials are looking for ways to maximize the current capacity.

CSL Biotherapies, an Australian company that is one of the five manufacturers making pandemic H1N1 vaccine for the US market, has a contractual obligation to produce vaccine first for its home country, Robinson said. Because Australia is in the midst of the Southern Hemisphere's flu season, the United States will work with CSL to ensure that it can deliver vaccine doses to both countries.

COMMENT: Well, this is not good news.  I was listening to the NBSB teleconference but I had a very bad line.  I did catch that they are having some delays but I didn't catch how many millions of doses.  45 million is a long way from 120 million.  Hmmm...


All 'safety concerns' are hypothetical.  If not, they'd be called side effects...

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by: SusanC @ Fri Aug 14, 2009 at 17:58:34 PM CDT

it's just as well that the ACIP

had made the alternate prioritization recommendations -

further prioritization only if supply limited (total 42M)

• pregnant women (4M)
  
• Household contacts and caregivers for children younger than 6 months of age (5M)
  
• Healthcare personnel and emergency medical services (14M)
  
• Children aged 6m through 4y (18M)
  
• Children aged 5y through 18 y with chronic medical conditions (6M)

They may have to stay with these groups until more vaccines become available.


All 'safety concerns' are hypothetical.  If not, they'd be called side effects...

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by: SusanC @ Fri Aug 14, 2009 at 18:01:28 PM CDT

[ Parent ]

bump for visibility n/t

All 'safety concerns' are hypothetical.  If not, they'd be called side effects...

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by: SusanC @ Mon Sep 21, 2009 at 19:32:05 PM CDT

well the numbers just keep on slipping

The CDC's Dr. Anne Schuchat said while 40 million doses had been anticipated for the end of October, only about 28 to 30 million doses would be available.

http://www.newfluwiki2.com/sho...

Also:

She also said more children had died in the space of a few weeks than usually die in an entire influenza season.

NOT good.  This is speculative, but I'm wondering if the chance of Plan B (see top diary) being activated - or at least seriously considered - may have increased from very low to low, possibly...

I hope I'm wrong, of course.  


All 'safety concerns' are hypothetical.  If not, they'd be called side effects...

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by: SusanC @ Fri Oct 16, 2009 at 15:09:32 PM CDT