Flu Vaccines, Adjuvants, Equity, Safety

[indigo girl]

When it comes to US swine flu vaccine policy, I'm not calling the shots, but if I were I'd do it differently than the current plan, which calls for a vaccine containing only viral antigen and no immunity boosting adjuvant. I opt for a vaccine with an adjuvant, probably the one that has been used for years in Europe, MF59. If I were to make a decision like that, I could well be making a mistake, because no one really can know at this point what is going to happen or not happen. We can only go on the best data we have coupled with some principles of what's right. On that basis and using my own fallible judgment I'd move as fast as I could to develop, distribute and deliver a swine flu vaccine that contained an immununity-boosting adjuvant.

Europe's adjuvanted flu vaccines don't appear to be any less safe than non-adjuvanted ones and are far more effective and efficient in the use of the scarce active ingredient, the viral antigen. It is availability of viral antigen that is limiting vaccine production. Unadjuvanted vaccines require much more viral antigen than those with adjuvants. We have written about adjuvants many time here (e.g., here), and recently Vincent Racaniello over at Virology Blog had a great post on the likely requirement for an adjuvant in any swine flu vaccine that could be given with only one dose. Obviously anything that will make more protection available to more people is a good thing, but like everything in public health, there is a balance to be struck and no sure way in knowing how to strike it.

Commentary continued at:

http://scienceblogs.com/effectmeasure/2009/09/swine_flu_vaccines_adjuvants_e.php

Please note that the comments following the Reveres post are worth reading as well at the link above. Many professionals have contributed their opinions.

The Editors of Effect Measure are senior public health scientists and practitioners. Paul Revere was a member of the first local Board of Health in the United States (Boston, 1799). The Editors sign their posts "Revere" to recognize the public service of a professional forerunner better known for other things.

[indigo girl]

Swine flu vaccines, adjuvants, equity, safety: more discussion

As we expected, yesterday's vaccine piece provoked a lot of discussion, almost all of it thoughtful and pertinent. Since we've already said we might be wrong, we thought we'd take some time to respond, using it as a way to keep thinking things through on our end. Writing is thinking and thinking is needed in this situation.

Over at FluTrackers.com (an excellent flu forum like Flu Wiki with highly informed people) there were a number of lengthy responses, most of them on the negative side. Since these folks follow events closely their opinions are also worth following closely. In addressing them I will also summarize the gist of yesterday's post, which represents the Reveres' joint opinion at this point.

1. We have been somewhat skeptical of the efficacy of influenza vaccination in the past. However reviewing the literature (we dealt with a good summary in this post recently) we have come to the conclusion that the vaccine works sufficiently that it is an important public health measure. Its efficacy varies but, depending upon the group, probably lies somewhere between 30% and 70%. In the case of a good match to a virus to which most of the population has no natural immunity, we believe 70% to be a good estimate considering the groups most at risk. This means that compared to an unvaccinated group, the vaccinated group will have 70% fewer infections. It means that 30% of those vaccinated who are exposed will still get the flu. Flu vaccine isn't even close to 100% effective like DPT or MMR. But even 30% reduction in infection in a pandemic is a Big Deal in terms of demands on services, lost work time and productivity, pain and suffering, and of course, mortality, so we don't think using the high end of efficacy makes much difference.

So that's the first point that may separate us from others. We think the vaccine will work and we base that on experience with seasonal vaccine where numerous randomized clinical trials have been done (see the Basta-Halloran review we linked above; here it is again). Take a look at it and make up your own mind about this. If you don't think the vaccine will work, then there's no reason to get it. We think it will work (based on our review of the science) and that it will make a big difference to how well communities who use it sufficiently will get through whatever might come next.

2. Safety, adjuvanted or unadjuvanted. Yesterday's post pointed out that it is not feasible to assure the advance safety of any product being consumed or administered to tens or hundreds of millions of people. No advance testing is possible for relatively rare adverse events that would still be numerous when that many people are exposed. But the mathematics of the adverse events versus the risks from flu, even if it is only the virulence of seasonal flu, is so overwhelmingly in favor of vaccination that we don't think this is a hard call. True, there are various guesses that have to be made about how many people are infected, what the CFR will be, how well the vaccine will work, etc., and while we tried to be pretty conservative in most of them (we did use a high end number for vaccine efficacy because we thought the data for similarly placed populations merited it, but even if we'd used the lowest efficacy vaccines come out far ahead), and you might differ with some of them. At least you know what we assumed. But the major point is this. If you want to wait for assurances of safety, then you better have a definition of "safety" that is determinable ahead of time or you are just saying you won't accept any vaccine. And for most of the rare events people talk about (e.g., Guillian-Barre Syndrome) there is no way to test for it in advance.

The rest of their commentary is here:

http://scienceblogs.com/effectmeasure/2009/09/swine_flu_vaccines_adjuvants_e_1.php

[indigo girl]

Adjuvant Effect on H1N1 Vaccine

http://www.virology.ws/2009/09/01/adjuvant-effect-on-h1n1-vaccine/

There has been a great deal of discussion about the use of adjuvants to improve the immunogenicity of vaccines against the 2009 H1N1 pandemic influenza strain. What effect do these compounds have on the immune response?

Adjuvants are compounds added to vaccines that stimulate the immune response. They are often used when the antigen is in short supply, or does not induce a good antibody response. Because the 2009 H1N1 pandemic influenza strains do not replicate well in eggs, it has been suggested that adjuvants be used to ensure that there is sufficient supply of vaccine.

A recent study demonstrates very clearly the effect of adjuvants on the immune response. Mice were immunized with egg-produced 2009 H1N1 influenza vaccine with or without the adjuvant MF59. A boost inoculation was given on day 21. Sera were taken on days 13 and 21 and the antibody response was measured by hemagglutination-inhibition (HI) assay. If you don't know how an HI assay works, please read my previous description. The results of the assay are shown in the figure.

One week after immunization with 0.5 micrograms of antigen, the average serum HI titer was 1:15 (bars labeled post1). This titer is barely higher than obtained when mice were immunized with buffer alone (PBS). The HI titer rose to 1:160 after the boost. When MF59 adjuvant was included, the first and second HI titers were significantly higher - 1:63 and 1:1280.

What do thes numbers mean? Protection of humans against seasonal influenza is generally believed to require a HI titer of 1:40 or more. Therefore when MF59 adjuvant is used in mice, one immunization is sufficient to confer protection against disease. Without adjuvant, two doses are required for protection.

Trials are ongoing in adults to determine the immunogenicity of 2009 H1N1 vaccines with and without adjuvant.

I know that many readers are concerned about the possible side effects of adjuvants. MF59 has been used for 12 years in seasonal influenza vaccines in Europe and is considered a safe adjuvant. However, the Centers for Disease Control and Prevention believes that the 2009 H1N1 vaccine will likely not be used with adjuvant.

[indigo girl]

Branswell: Feds Between Rock & Hard Place On Vaccines

In the race to get pandemic vaccine into Canadian arms, public health and vaccine regulatory authorities in this country find themselves the reluctant filling in a rock-and-a-hard-place sandwich, knowledgeable observers say.

Doctors who've seen how desperately sick some swine flu patients become are pressing authorities to further fast-track vaccine approval. But a large portion of the public appears reluctant to take the vaccine, a situation that could worsen if fast-tracking deepens suspicions about the product's safety.

Individuals and organizations concerned about global equity are urging countries with vaccine contracts to stretch supplies by using boosting compounds called adjuvants so developing countries can also get some serum. But the decision to use an adjuvant is being blamed - unfairly, federal officials say - for the fact Canada may not start vaccinating until a month after the U.S. and Britain.

http://afludiary.blogspot.com/2009/09/branswell-feds-between-rock-hard-place.html