The GlaxoSmithKline Pre-Pandemic Vaccine
First, a caveat, I am not an immunologist, so please take my analysis of this vaccine with a large grain of a salt.
GlaxoSmithKline (GSK) has recently announced that...
...its candidate H5N1 adjuvanted pre-pandemic vaccine, Prepandrix™, designed for use in advance of an officially declared influenza pandemic, has received the first Positive Opinion from Europe’s Committee for Medicinal Products for Human Use (CHMP) for an influenza pre-pandemic vaccine.
Exactly what is a pre-pandemic vaccine? First, it is *not* a universal flu vaccine. That is based on a different conceptual approach and is still experimental. The Prepandrix vaccine is basically a regular flu vaccine on steroids. And the steroid is a proprietary adjuvant. As many know, adjuvants help stimulate the immune system to respond more strongly to the viral protein part of the vaccine. The adjuvant used by GSK is apparently so strong that it stimulates the immune system to produce antibodies that will cross-react with multiple strains of H5N1, not just the one contained in the vaccine.
In one of the pivotal trials, the vaccine, which utilizes the antigen from the H5N1 Vietnam strain, demonstrated a 4-fold increase in serum neutralizing antibodies in 77.1%, 75% and 85% of subjects against three distinct H5N1 strain variants, Indonesia, Anhui and Turkey respectively.
The press release emphasises that this is an adjuvanted vaccine but does not state that the adjuvant is responsible for the cross-reactivity of the vaccine. The paper that they cite supporting their claims might have more information, but it has not yet been published. It will appear in PLoS One this month. If that paper proves my interpretation wrong, I will revise this blog.
Based on the references cited in the press release, this would appear to be the same vaccine that was found to protect 96% of ferrets infected with an otherwise lethal dose of H5N1 (Barres et al.). The vaccine used in the ferret study indicates that the adjuvant was a
proprietary oil-in-water emulsion based Adjuvant System manufactured by GlaxoSmithKline (GSK) Biologicals
Since the adjuvant is proprietary, we cannot know for sure what it is, but I think it is likely a squalene-containing mixture similar to MF59. Studies as far back as 2005 have shown that MF59 greatly increases the cross-reactivity of H5 vaccines (Stephenson et al.).
Why doesn't GSK state the nature of the adjuvant since this is likely key to the effectiveness of the vaccine? Well, it could be because they want to keep it a trade secret, but I think it is likely that most people in the business know that it is MF59 or a related compound. Another possibility is that they fear if they mention that it is a squalene-containing adjuvant they will be attacked by believers in a conspiracy theory proposed by Gary Matsumoto in his book: "Vaccine A: The Covert Government Experiment That's Killing Our Soldiers—and Why GI's Are Only the First Victims". I have previously written about this book here and here and won't say anything further about it except to suggest that Dr. Supari doesn't have anything on Gary Matsumoto when it comes to conspiracy theories involving the US government.
Does that mean I am convinced that GSK pre-pandemic vaccine is perfectly safe? In a word - no. According to the GSK press release
The submission dossier for this proprietary adjuvanted pre-pandemic vaccine, which received the Positive Opinion today, was based on a series of data from numerous clinical and pre-clinical trials which evaluated the safety, reactogenicity, immunogenicity and cross-protection induced by the candidate pre-pandemic vaccine.
Note, that although they say safety was evaluated, they do not say it is perfectly safe. Nor can they. All flu vaccines carry some risk. These range from the minor, a sore arm, to the life-threatening Guillain-Barre disease. Guillain-Barre disease associated with flu vaccine is estimated to manifest itself approximately 13 days after vaccination (Haber et al.). The incidence of Guillain-Barre disease after regular flu vaccine is estimated at about 1 in a million (Haber et al.). Because adjuvants increase the cross-reactivity of vaccines, it is possible that a vaccine with a strong adjuvant may be more likely to result in an auto-immune disease such as Guillain-Barre. Thus, it would be to the benefit of GSK to name the adjuvant used in Prepandrix and provide the numbers of people who have received it. Hiding behind the "proprietary" mask is unwise, imo.
So, would I take this vaccine? Well, given that I think a high CFR pandemic is more than 50% likely, then yes, without a question. Although I strongly agree with those who say that Americans are over-drugged and that no vaccine or drug is a magic bullet, the risk from an adjuvanted flu vaccine is likely very small compared to the risk of a high CFR pandemic, imo.
The fact that the European Medicines Agency has rendered a positive opinion on this vaccine is significant, imo. They point out that:
The most common side effects are injection side reactions, headache, tiredness, fever,
aching muscles and joint pain.
So, they are aware that the vaccine is not without risk. Yet, they also suggest that:
The benefits with Prepandrix are that it can mount an appropriate immune response in individuals that are immunologically naïve against the vaccine strain and the assumption that vaccination with Prepandrix will provide a clinically useful degree of cross-protection against the strain that causes the next pandemic.
This suggests to me that they consider the risk that H5N1 will cause the next pandemic to be quite high. According to GSK
A number of national governments have expressed significant interest in stockpiling our candidate pre-pandemic H5N1 vaccine...
It would be interesting to know which governments those are. And why the sudden interest in a pre-pandemic vaccine. It is pre-pandemic, right?
Saturday, February 23, 2008
