There have been many interesting responses to my recent post, “Are you receiving the influenza 2009 H1N1 vaccine?” Some individuals have already been immunized or plan to do so shortly. Others are concerned about the safety and efficacy of the monovalent preparations. As pointed out recently in a Nature editorial, “Mass-vaccination campaigns…must take public concerns into account”, and “officials should focus on providing people with the information they need to make good choices for themselves.” Here are some facts about the influenza H1N1 vaccine for those who haven’t yet made up their minds whether or not to be immunized.
Four companies are licensed to produce the 2009 H1N1 influenza vaccine for the US – CSL Limited, Novartis Vaccines, Sanofi-Pasteur Inc., and MedImmune. The US Food & Drug Administration has published on their website the package insert for each product. These are multipage documents with a good deal of information, including indications, dosage, contraindications, adverse reactions, and the results of clinical studies. Links to the package insert for each vaccine are listed below.
- CSL Limited – Afluria Influenza A (H1N1) 2009 Monovalent Vaccine (pdf)
- Novartis Vaccines and Diagnostics – Fluvirin Influenza A (H1N1) 2009 Monovalent Vaccine (pdf)
- Sanofi Pasteur, Inc – Fluzone Influenza A (H1N1) 2009 Monovalent Vaccine (pdf)
- MedImmune LLC – Flumist Influenza A (H1N1) 2009 Monovalent Vaccine (pdf)
For example, the package insert for Afluria indicates that the vaccine is supplied as a sterile suspension for intramuscular injection in two forms: a 0.5 mL preservative-free, single-dose, pre-filled syringe; and a 5 mL multi-dose vial containing ten doses. Thimerosal, a mercury derivative, is added as a preservative in the multi-dose vial; each 0.5 mL dose contains 24.5 micrograms of mercury.
The results of two clinical studies on the safety and efficacy of Afluria are also reported: a US study of 1,357 individuals, and a UK study of 275 subjects. No serious adverse effects were reported in either study. The seroconversion rates are included in the form of hemagglutination-inhibition titers.
I encourage everyone to read at least one of these package inserts to become familiar with the extent to which these vaccines have been tested in people. If any aspects of these documents are not clear, don’t hesitate to contact me.
Note added after publication: It was pointed out in the comments that the safety and efficacy data reported in the package inserts were obtained with the seasonal influenza vaccines, Afluria, Fluvirin, Fluzone, and Flumist, not the 2009 monovalent H1N1 vaccine. My apologies for implying otherwise. I will locate the safety and efficacy data for the monovalent H1N1 vaccines and update the post with that information.
Second addendum: According to the FDA, the influenza A (H1N1) 2009 monovalent vaccine has been tested in the same way as new seasonal vaccines that are produced each year. The inactivated influenza A (H1N1) monovalent vaccine manufactured by CSL Limited was tested in 120 adults. By day 21 after vaccination, HI antibody titers of 1:40 or more were observed in 116 (97%) of 120 adults who received a 15 μg dose. Injection site tenderness or pain was reported by 46% of subjects, while 45% of the subjects reported one or more systemic symptoms (headache, malaise, or myalgia). These observations are similar to those observed in testing of seasonal influenza vaccines. The preliminary results have been published.
The Sanofi Pasteur 2009 H1N1 vaccine has been tested in children aged 6-35 months, 3-9 years, and 10-17 years, and the results have been reported by NIAID. After immunization with a single 15 μg dose of vaccine, 25%, 36% and 76% of individuals in each age group developed HI antibody titers of 1:40 or more. No information on adverse effects have been provided.
Medimmune and Novartis have reported immunogenicity and safety study results similar to those observed for seasonal vaccines, but the data have not yet been released.
Although the 2009 H1N1 vaccines produced by all four manufacturers have been approved by the FDA, all the data used for approval have not yet been published or released. As soon as these data are available I will pass them on.
“ADVERSE REACTIONS information is based on studies conducted with seasonal trivalent Influenza Vaccine …” this line is written in all the pdf files that you alluded to in your post, does this mean that safety studies are not based on the new H1N1 strain?
You are absolutely right – the monovalent H1N1 data are not included
in the package insert. I've updated the post to indicate this and will
add the relevant data as soon as possible. Thank you for pointing this
out.
Does the monovalent H1N1 data exist? Were the studies done?
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Question: do we know the manufacturing locations for U.S. 2009 H1N1 suppliers (CSL Limited, Novartis, Sanofi Pasteur, & MedImmune)?
David
Yes, the data do exist for monovalent H1N1 releases in the US – the details are in the post.
I'm not certain where the US vaccines are made, except that only about 20% comes from the US. CSL has plants in Australia and also fills vials in Illinois and Germany. The Novartis and Sanofi vaccines are made in Europe, and I believe at least some of the MedImmune vaccine is made in Pennsylvania. Take all of this with a grain of salt – perhaps others have better information on this question.
Yes – I have included the information in the revised post. All four
have been tested; data are available for two.
There was some testing with 5.25 mcg of virus stuff plus adjuvant. Why did the Canadian gov't decide they could safely go to 3.75 mcg plus adjuvant.
where is it produced?
As an interested lay person, I am having trouble interpreting Section 14.2 of MedImmune's Influenza Nasal Spray Vaccine, and the chart that follows this section. The results from this chart do not seem very impressive for effectiveness. If given a choice, would an adult in this age group be better off with a shot instead of the nasal spray?
Because the lower dose was shown, in clinical trials, to induce high rates of seroconversion commensurate with protection.
That Flumist study wasn't the best because they didn't test directly for influenza virus. I suspect that is one explanation for the low percent reduction in illness; a good amount of the illness that occurred might not have been influenza and of course would not have been prevented by the vaccine. If I had a choice of vaccine I would take Flumist because as an infectious preparation it most closely mimics a natural infection. Other studies have shown Flumist to be as good or better as the inactivated vaccine at preventing infection.
Makes perfect sense. But I haven't seen anything on GSK Canada/ID Biomedical that shows they tested at 3.75mcg.
Off topic I know.
I'm trying to find influenza infection rates in different settings to plug into this computer model. It's the best argument for flu vaccination I've seen.
http://www.shodor.org/ssep/stu/activities/foren… . Can you point me in the right direction.
But it did worse in healthy adults.
http://content.nejm.org/cgi/content/full/361/13…
The data are in part 4 of the Arepanrix product info leaflet, linked in the post. 3.75 micrograms, with adjuvant, 100% seroprotection rate.
That's correct – the inactivated vaccine was 50% better. Probably because those adults had been previously infected with a strain of influenza related to the vaccine, hence preventing proper replication of the vaccine. This year's H1N1 is so novel that it should give much better protection.
Boot to the head, Somehow I missed it when I was looking at it earlier.
Thanks.
If 93.9% of those treated with 15mcg have a seroprotection 1:40 or greater then why does it matter if they were seropositive before and then only qualify as seroconverted if they had a 4 fold increase increase in titre. I poked around and don't understand that. Why isn't the titre number > 1:40 sufficient. As a Canadian, faced with evil adjuvant idiocy, explaining the benefit of AS03 is very important.
Immune response to A/California/7/2009 (H1N1)v-like 21 days after 1st dose
Non-Adjuvanted H1N1 Vaccine (15 µg HA) N=66
Seroprotection rate 93.9%
Seroconversion rate 84.8%
Seroconversion factor 31.0
AS03-Adjuvanted H1N1 Vaccine (3.75 µg HA) N=61
Seroprotection rate 100%
Seroconversion rate 96.7%
Seroconversion factor 43.3
I am a Canadian GP, 34 wks pregnant, with a 2year old son…..very concerned on safety of our adjuvanted vaccine (from GSK) and interested to know how it compares to Sanofi's unadjuvanted and other US vaccines.
i would like to know everything that is in this needle before i even think about my 5 children
and my husband and i getting this h1n1 vac needle??
could u please help me with all the right info my e-mail is
jodyannd29@hotmail.com
List of ingredients: http://www.novaccine.com/specific-vaccines/vacc…
Here's a CDC sourced document for ingredients: http://www.cdc.gov/vaccines/pubs/pinkbook/downl…
It's better. It's got a 10% higher seroconversion rate in healthy adults under 60 than the standard US or non-adjuvanted Cdn 15 mcg dose. The practical difference is that your arm will hurt more if you get the 3.75mcg plus AS03 dose. A similar adjuvant, MF59, has been used in more than 40 million European vaccinations.
For us non-techies with kids…who want to avoid thimersal….can you give us a list of H1N1 vaccines that are free of this preservative? Thanks so much by the way for your time.
I'm 13 years old, and my school is giving out the H1N1 vaccine but i'm not to sure if I should get it or not. Could you help me? If you could thank you very much, but if not it's okay.
I have a three y.o. child who has egg allergy (positive skin test, never exposed) and is prone to febrile seizures. We all were sick 4 or 5 times in a last two months (since she started preschool) and once with a flu-like symptoms. Would you recommend vaccinating her anyway?
Question: is it possible for antihistamines to alter antibodies production in response to either virus or vaccine?
The H1N1 vaccine has already been given to millions, and there has been almost NO SAFETY data released to date. Given that all of the vaccine manufacturers are being held blameless for any adverse effects (you can't sue them), don't you think that's an alarming omission?
There is a nasty, divisive tone to this argument. Apparently, those who are pro-vaccine believe that those who are anti-vaccine are radical conspiracy theorists. From where I'm standing, a parent who decides not to have their children inoculated with this vaccine is just being smart.
The whole argument seems to be political and artificial – why would anybody want to make a choice between vaccinating and not vaccinating in general when it is so much wiser to think in terms of safety of each vaccine versus possible severity of the disease. There is no pure black or pure white in nature…
Flumist is the only H1N1 vaccine that is not available with thimerosal. The inactivated vaccines made by CSL Limited, Sanofi, and Novartis are made in two versions: one without thimerosal and one with the preservative.
Both egg allergies and recent febrile seizures are contraindications for immunization with influenza vaccine.
To my knowledge antihistamines do not interfere with antibody production.
I completely understand your sentiments about the divisive tone in the pro- and anti-vax arguments. I try to present science-based information and allow everyone to make there own decisions. The H1N1 vaccine has been tested, and the data have been released as noted in this post. It is made in the same way as every other influenza vaccine for the past 40 years, and for this reason does not need to be tested in tens of thousands of individuals. And you can always sue vaccine manufacturers.
Please, correct me if I am wrong but from what I have read it seems like the vaccines are tested only by manufacturers… rather than by independent agencies of any kind.
Correct, the influenza vaccines are tested by the manufacturers. The results are provided (in the US) to the FDA which is responsible for approving and releasing the vaccines.
I was just reading the Arepanrix package insert and noticed the following:
“In the first study, there was an increased incidence of fetal malformations with markedly medially thickened/kinked ribs and bent scapula as well as an increased incidence of dilated ureter and delayed neurobehavioral maturation. In the second study, there was an increased incidence of post-implantation loss, and the fetal variation of dilated ureter. Not all findings were observed in both studies, and hence the toxicological significance is uncertain.”
Seems to me that, considering the above and the lack of data on pregnant women and their babies, it would be reckless to declare the adjuvanted vaccine safe for pregnant women.
http://www.hc-sc.gc.ca/dhp-mps/prodpharma/legis…
You neglected to say that the toxicity studies were conducted in rats.
Furthermore, “Not all findings were observed in both studies, and
hence the toxicological significance is uncertain.” I haven't seen the
study results in rats so I can't evaluate them. But remember that
Health Canada has written: “The Government of Canada ordered
unadjuvanted vaccine to offer pregnant women, since adjuvanted vaccine
has not been tested in this group. The decision to purchase
unadjuvanted vaccine for pregnant women was based on a desire to err
on the side of caution.”
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I received the H1N1 Flumist one week after having a C-section. At that time I was anemic due to the surgery and was on antibiotics for a UTI. With all of these underlying issues, will I be properly protected? or should I receive the flu shot as well?(the vaccine info sheet said not to use Flu Mist if you are anemic or have any health conditions) (Also, it felt like the entire mist went straight down the back of my throat instead of staying in my nasal passages.)
The advice not to receive Flumist if your anemic or have health
conditions is mainly to protect you; these conditions (unless they
include immunosuppression) should not affect your immune response. One
of the things you are told to do when receiving Flumist is to avoid
swallowing after inhaling. But it's a normal response to feel that a
lot goes down the throad; in reality a lot also remained in your upper
tract. Re-immunization should not be needed.
where does it exist today
I am looking for studies showing the efficacy of H1N1 Flumist compared to placebo and compared to the injected form. I have not been able to find any.
I went ahead and recently took the Flumist based on the the same reasons you suggested. However, the lack of any published laboratory evidence supporting my decision makes me suspicious that the company possibly has results they aren't releasing because their product did not produce a robust immune response in the test subjects.
What do you think?
The most recent study was published in NEJM: N Engl J Med. 2009 Sep
24;361(13):1260-7. Let me know if you can't get this article. Other
studies include J Adolesc Health. 2009 Jul;45(1):91-4. Epub 2009 Apr
2.; a review article here: Influenza Other Respi Viruses. 2008
Nov;2(6):193-202.
Thanks for your response. I was really hoping to find studies showing results for the current pandemic H1N1 monovalent version of Flumist. I had reviewed the abstract of the afore-mentioned NEJM: 2009 Sep article which showed for the influenza A (predominately H3N2) seasonal flu, that:
“The absolute efficacy against the influenza A virus was 72% …for the inactivated vaccine and 29% … for the live attenuated vaccine,”
It was this 72% vs 29% disparity that weakens my confidence in the current H1N1 pandemic strain. Even the package insert for the current H1N1 produced by MedImmune does not include any references whatsoever to titer responses of the monovalent vaccine in question but instead, defers the reader to older seasonal flu mixes, most of which are in the pediatric population. Although some of the pediatric polyvalent results are quite satisfying, I am hesitant to extrapolate those findings to the current H1N1 Flumist.
It is difficult to believe that MedImmune has not done any lab studies of titer responses in adults using the 2009 monovalent H1N1. I do not wish to feed into the distrustful mentality that the general public has for vaccine manufacturers, so in some ways I am reluctant to bring it up, but this glaring omission is quite perplexing.
Thanks for your response. I was really hoping to find studies showing results for the current pandemic H1N1 monovalent version of Flumist. I had reviewed the abstract of the afore-mentioned NEJM: 2009 Sep article which showed for the influenza A (predominately H3N2) seasonal flu, that:
“The absolute efficacy against the influenza A virus was 72% …for the inactivated vaccine and 29% … for the live attenuated vaccine,”
It was this 72% vs 29% disparity that weakens my confidence in the current H1N1 pandemic strain. Even the package insert for the current H1N1 produced by MedImmune does not include any references whatsoever to titer responses of the monovalent vaccine in question but instead, defers the reader to older seasonal flu mixes, most of which are in the pediatric population. Although some of the pediatric polyvalent results are quite satisfying, I am hesitant to extrapolate those findings to the current H1N1 Flumist.
It is difficult to believe that MedImmune has not done any lab studies of titer responses in adults using the 2009 monovalent H1N1. I do not wish to feed into the distrustful mentality that the general public has for vaccine manufacturers, so in some ways I am reluctant to bring it up, but this glaring omission is quite perplexing.