# Hydrobates

A mathematician thinks aloud

## Influenza vaccines

I have recently been reading about influenza vaccines and I am summarizing some of the information I found here. I start with some remarks on the classification of influenza viruses. The first distinction is between influenza A and influenza B viruses. The former are classified further into subtypes HnNm for numbers $m$ and $n$. Well-known examples are H5N1 (which includes the recent ‘bird flu’) and H1N1 (which includes the pandemic of 1918 and the current ‘swine flu’.) Influenza B does not carry a pandemic threat and will not be considered further here. Every year a vaccine is produced for the seasonal flu epidemic (in fact two – one for the southern and one for the northern hemisphere). It is trivalent, being directed against three types of virus. In recent years this has always been of the form H3N2 + H1N1 + B. In particular this is the case for the present vaccine for seasonal flu. It is not expected that this vaccine will be effective against the pandemic H1N1 swine flu. Thus a separate type of vaccine has been developed for that. In the classification H and N stand for haemagglutinin and neuraminidase, two proteins which occur on the surface of the virus and come in different forms in different strains. These are the main molecules of the virus recognized by antibodies. They are involved in the processes by which the virus enters and leaves host cells, respectively.

Next I come to some details concerning the vaccines themselves. I concentrate on those being applied in Germany since this is what would be relevant for me if I got vaccinated myself. I get the impression that there are a lot of unreliable and misleading statements on this subject in the media and so some care is necessary in judging the information available. On the web page of the Paul Ehrlich Institute there is a list of vaccines against seasonal flu approved in Germany in this season. Twenty products are listed. All are classified as inactivated. This means that if manufactured successfully the vaccine cannot lead to any reproduction of the virus. In other words the vaccine uses (parts of) ‘dead’ virus particles. Three of the vaccines are described as ‘virosomal’ which means that they can be administered as a nasal spray. Presumably all the others are administered by injection. Two of them include an adjuvant, a substance which is intended to amplify the immune response. This is one theme which has led to recent controversy in connection with swine flu vaccines and I will return to it later. One vaccine (Optaflu) is said to be produced in cell culture. This is connected to another theme of recent controversy, with discussion in the media about vaccines produced using cancer cells.

Having looked at the vaccines for seasonal flu I now come to swine flu vaccines.The web page of the Paul Ehrlich Institute lists three vaccines approved in Germany for the new H1N1 influenza. These are called Celvapan, Focetria and Pandemrix. All three are inactivated. The second and third include an adjuvant. The first is produced in cell culture. Apparently Pandemrix is intended to be the main vaccine used in Germany. There is a statement on the web page of the PEI that, contrary to some claims in the media, this is also what has been used to immunize the employees of that institute. There has been discussion of the fact that apparently politicians and the army are to get Celvapan so that a debate about ‘second class citizens’ has taken place. This is likely to obscure the real issues. Consider next the topic of adjuvants, substances which have recently been getting some bad press. An adjuvant is a substance which increases the reaction of the immune system to an antigen given as a vaccine. A stronger immune response can lead to better immunity for a given amount of antigen. It could also in principle lead to an excessive and damaging immune reaction although I have not seen any convincing evidence that this has happened in the context of the swine flu vaccine. It would be wrong to think that the name adjuvant denotes a particular class of substances. Many different things can act as adjuvants. What they have in common is that they activate some part of the immune system. Given that the immune system is so interconnected this can lead to a stronger immune response on a wider basis. An interesting example is that in the combination vaccination for diphtheria, whooping cough and tetanus the diphtheria toxoid acts as an adjuvant for the other two vaccinations. What has just been said about the nature of adjuvants makes it clear that it is nonsensical to say that all adjuvants are bad. Each one must be considered on its own merits. In the case of Pandemrix the adjuvant is called AS03. I am unable to give any judgement on it, since I have not spent enough time studying the question. In any case my basic assumption is that what has been approved by the relevant medical authorities is OK. In other words, for these things my default attitude is trust, not mistrust.

Now to the question of the cancer cells. Celvapan is produced using a cell line called Vero cells which is derived from monkeys. It seems that these cells arose from kidneys of normal monkeys and have nothing to do with cancer. Usually normal cells can only undergo a limited number of divisions while cancer cells can be immortal. Vero cells are not cancer cells but they do seem to be able to survive in cell culture for an unlimited time. I do not understand how this works. It may be noted that Vero cells have been used in a routine way to produce millions of doses of polio vaccine and so there has been ample opportunity to discover any possible dangers associated to their use. In the production of Optaflu a cell line called Madin-Darby canine kidney cells is used. This looks like the same kind of tissue as with Vero cells, except derived from a different animal. I have not found a reference anywhere claiming the use of cancer cells in this context which looks trustworthy.

To finish, here is a piece of news from the web site of the ECDC in Stockholm. In the Ukraine there have now been 500 000 reported cases of acute respiratory illness and it seems that the expert opinion (cf. also the WHO website) is that most of these are related to the new H1N1 influenza. There have been 86 deaths reported from there. So it seems that the pandemic is alive and well.

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This entry was posted on November 5, 2009 at 9:03 pm and is filed under diseases, immunology. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.

### 6 Responses to “Influenza vaccines”

1. Uwe Brauer Says:
November 10, 2009 at 4:13 pm | Reply

Hello

I don’t hope to start a “flamewar” on this, but the article
http://www.spiegel.de/wissenschaft/mensch/0,1518,druck-637567,00.html
unfortunately in german, gives some interesting insights.

Tom Jefferson an expert in epidemics from the Cochrane Collaboration claims, that based on statistical analysis only 7% of all the infection which have flu like symptoms are actually caused by the by the influenca virus.

Moreover washing the hands is the best protection.

It calls his attention (and I must say mine) that the influenca virus is unique among all the other groups of virus in the sense that it is the only one for which a vaccine has been developed.

Uwe Brauer

2. hydrobates Says:
November 10, 2009 at 9:40 pm | Reply

Hello Uwe

I am not sure you should believe everything you read in ‘Der Spiegel’ on this
subject. You might like to look at the comments on an article there on the home page of the Paul Ehrlich Institute (http://www.pei.de/)

By the way, there must be some misunderstanding with the ‘no vaccine for a virus’ statement. For instance, I got vaccinated against yellow fever before I visited Cameroon.

• Uwe Brauer Says:
November 17, 2009 at 4:27 pm | Reply

Hello Alan,

first I think I have to clarify a misunderstanding.
I did not want to claim that there are no vaccine for virus. Yellow feaver is one example small pox another. Now the claim is about virus which can cause flu like diseases. As I understand the information whose links I will provide below, correctly there are around 200 viruses which can causes these illnesses.
http://www.spiegel.de/international/world/0,1518,grossbild-1594590-637119,00.html states:
29% of the infections are caused by rhinovirus,
14.4 by coronavirus
3.6% by RSV
7% by influencia
and the rest
46% by virus unknown to man.

However there is another issue with I find annoying: The WHO has changed its definition of pandemic! The old definition was a new virus, which went around quickly, for which you didn’t have immunity, and which created a high morbidity and mortality rate. Now the last two have been dropped, and that’s how swine flu has been categorized as a pandemic.

Here are some links in addition

http://www.bmj.com/cgi/content/full/333/7574/912

http://www.jefferson.edu/information/

Jefferson’s interview in english:

http://www.spiegel.de/international/world/0,1518,637119,00.html

Uwe

3. hydrobates Says:
November 18, 2009 at 10:59 pm | Reply

This evening I went to a lecture on pandemics at the Einstein Forum in
Potsdam. The speaker was Stefan Kaufmann who is director at the Max Planck Institute for Infection Biology in Berlin. I have a very high opinion of him and the lecture, which was excellent, only served to reinforce this.His main subject was tuberculosis, not swine flu, but he said some things which were relevant to your comments. I should mention that this talk was not mainly about medical science, but rather about public health policy and its relations to economics and politics. He mentioned the fact that the WHO changed its definition of ‘pandemic’ at a critical moment, confirming what you mentioned in your comment. His reaction was that it was unwise of them to do that since it just led to making people suspicious. In that context he said that reacting to a disease with a vaccine is 10 per cent medicine and 90 per cent mass psychology. Another interesting remark concerned adjuvants. He believes that with a sufficiently good adjuvant (which does not yet exist) vaccinations to the seasonal flu could be made to last ten years instead of one. To finish let me mention that Kaufmann has written a book entitled ‘Waechst die Seuchengefahr? Globale Epidemien und Armut: Strategien zur Seucheneindaemmung in einer vernetzten Welt’ of which I bought a copy. [For readers who do not speak German: there is also an English version with the title 'The new plagues. Pandemics and poverty in a globalized world']

4. Some vaccinations I have had « Hydrobates Says:
November 30, 2009 at 9:08 am | Reply

[...] consult. I will start with hepatitis A and B since that involves some themes which I mentioned in a previous post on influenza vaccines. A point I want to make is that the swine flu vaccines about which there has been so much public [...]

5. The immortal Henrietta Lacks « Hydrobates Says:
January 23, 2010 at 9:41 pm | Reply

[...] By hydrobates I find immortal cell lines a fascinating topic and I mentioned the subject in a previous post on influenza vaccines. From time to time I had heard about HeLa cells. I knew that this was a cell line derived from [...]

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