| First of all, Guillain-Barre Syndrome is an autoimmune neurological disease characterized by acute onset of muscle weakness or paralysis. Patients develop antibodies to certain molecules (anti-ganglioside antibodies) present in large quantities in nerve tissue, possibly as a result of molecular mimicry ie structural similarity between bacterial or viral antigens and the body's own molecules.
From the paper:
Patients with GBS develop anti-ganglioside antibodies that are implicated in the pathogenesis of this disease. Antibodies to a number of different complex gangliosides, includingGM1,GD1a, GD3, GT1a, and GQ1b, can be detected in patients with GBS [10]. Infections with several agents are associated with the development of GBS [11], and Campylobacter jejuni, a common cause of bacterial gastroenteritis, is one of the most frequently identified bacterial pathogens associated with the development of GBS [12]. It has been deduced that the development of GBS after C. jejuni infection is the result of molecular mimicry between the bacterial surface lipooligosaccharide (LOS) expressing
ganglioside-like epitopes and relevant targets in peripheral nerves [10, 13].
Because influenza vaccines are grown in eggs, and because eggs are frequently contaminated with C. jejunei, the researchers set out to discover whether vaccine contamination with C. jejunei might be the cause of the GBS outbreak.
Here's what they did. They obtained unopened vaccine samples from 11 vaccine lots containing the 1976 swine flu vaccine, from 3 different manufacturers. First they tested these vaccines for haemagglutinin inhibition (HAI) test, to prove they still had HA activity. Then they vaccinated mice with these vaccines, and tested their serum samples for antibodies to C. jejunei. They did NOT find any such antibodies. They also ran some PCR tests, again for C. jejunei, with the vaccine samples, and didn't find anything either.
So, that showed them, the 1976 vaccines were NOT contaminated with C. jejunei. So far so good.
But what they did find was rather disconcerting. They found that even though no c. jejunei was present, the mice all developed anti-ganglioside antibodies, just like patients with GBS would.
After that, they tested 2 other influenza vaccines, from 1991-92, and 2004-05 flu seasons. They found similar results - the mice did NOT develop antibodies against C. jejunei (showing there was no contamination) but they DID develop anti-ganglioside antibodies.
To verify this in a different way, they did 2 other tests:
1) they tested the vaccine samples with anti-ganglioside anti-sera, which would be expected to react to the presence of gangliosides or molecules that mimic gangliosides. They found that the same vaccine lots reacted with these anti-sera, showing that the vaccines indeed contain some substance that acts as ganglioside mimics.
2) They tested commercial anti-ganglioside anti-sera, for HAI activity, and again found positive results, showing that there may indeed be some mimicry between ganglioside and HA molecults.
So, up to this point, they have shown that there was something in those vaccines that had ganglioside mimic characteristics, and that this may well be the HA molecule itself (since commercial anti-ganglioside anti-sera had HAI activity!). So far, the tested vaccines were all subunit vaccines.
Finally, they tested a recombinant HA vaccine, ie a vaccine that ONLY contains the HA molecule and nothing else. This time they used the H5 vaccines, generated against the 1997 Hong Kong virus, and another against the Vietnam 2004 virus. Again they got the same results - the HA vaccine triggered the development of anti-ganglioside antibodies in vaccinated mice.
So what does this study tell us? If the results are correct (it's always prudent to get other researchers to repeat the study), it shows that the HA in influenza virus itself, irrespective of which virus, has some properties that can trigger anti-ganglioside antibodies. Although the mice did not develop symptoms of GBS (we know that mice are not good models for human disease) this is a worrying finding. Current vaccination strategies, whatever vaccine you use, focus on the HA as the main target antigen. The aim is to produce robust immune response against the HA. If, as this study suggests, HA is in fact a molecular mimic for molecules in our nervous system, it may not be a smart idea to stimulate strong antibody reactions against HA, after all!
In the words of one FDA scientist, there may be a good reason why we are not MEANT to have strong immune responses against influenza viruses! Of course, this is speculative at this point, but it really is something worth watching IMO. |
