| The 1976 vaccine was correlated with an increased incidence of GBS, which, according to a recent study described earlier, may be due to molecular mimicry, between the HA molecule and human gangliosides, proteins that permeate our nervous system.
Ideally one would want to repeat the study and confirm the findings, at least, but we are in a pandemic, and tptb are in a rush to provide vaccines for millions of people. In the absence of further data, is there anything we can learn, even tentatively?
If HA is indeed a biological mimic, it could account for the very small but increased incidence of GBS after flu vaccines in general, and the 1976 one in particular. The effect of biological mimicry is, by definition, dependent on how closely the molecules are similar. To the extent that different HAs from different flu viruses have slight differences in conformation, they would probably have varying degrees of mimicry, such that vaccines made from these HAs may therefore have varying ability to induce GBS. Which is compatible with the varying incidence of GBS reported after seasonal flu vaccinations in different years. (see Haber 2004, Guillain-Barré Syndrome Following Influenza Vaccination)
As an extension of that, can we also say that any HA that is similar to 1976 (like the current H1N1) may be more likely to induce GBS? We can't answer that question, because we don't know what other components are/were important in the pathogenesis of GBS in 1976.
For example, it was widely believed that the 1976 vaccine had a particularly high endotoxin content, a bacterial by-product (or impurity) of the vaccine manufacturing process, which may have contributed to the higher GBS rate.
One very interesting study Geier 2003, Influenza vaccination and Guillain Barre syndrome had the following findings:
- increased risk of acute GBS and severe GBS after influenza vaccination as compared to adult tetanus-diphtheria (Td) vaccine - which was chosen as control since an IOM review concluded "the evidence favored a causal relationship" between GBS and Td vaccination.
- Influenza vaccines contained from a 125- to a 1250-fold increase in endotoxin concentrations in comparison to an adult Td vaccine control
- Endotoxin concentrations varied up to 10-fold among different lots and manufacturers of influenza vaccines, as shown in the chart
- There was statistically significant variation in the incidence of reported GBS after vaccination from vaccines from the different manufacturers. Unfortunately, the identity of specific manufacturers for this test could not be revealed, as the CDC deemed this information to be 'proprietary and confidential' ;-( , hence we cannot determine from the data whether those vaccines with higher endotoxin content were associated with higher GBS report rates.
Nevertheless, the authors still concluded that The biologic mechanism for GBS following influenza vaccine may involve the synergistic effects of endotoxin and vaccine-induced autoimmunity.
Here, the question gets interesting, because different kinds of bacterial endotoxins, eg from E. coli, have been used as vaccine adjuvants. The intranasal flu vaccine that caused a spate of Bell's palsy cases leading to its withdrawal, was adjuvanted with endotoxin from E. coli. The novel adjuvant AS04, made by GSK and used in Hepatitis B (Fendrix) and HPV (Cervarix) vaccines in Europe, also contains MPL, which, according to this paper with a rather triumphant title, Vaccine adjuvants: the dream becomes real, "comes from the cell wall LPS (=lipopolysaccharide) of Gram-negative Salmonella minnesota R595".
In other words, if endotoxin was a significant factor in vaccine-induced GBS in 1976, the whole episode may have been a demonstration of the effect of a naturally-occuring adjuvant on induction of autoimmunity.
Here's my question. And please don't fault me for asking 'rhetorical' questions - I'm asking them because they are real, I don't know the answer, but the answer may be relevant to our assessment of the safety of using novel adjuvants in flu vaccines in the current pandemic.
If endotoxin was acting as an adjuvant and was partly responsible for the increased incidence of GBS in 1976, would much more powerful vaccine adjuvants deliberately formulated to enhance the immune response to the HA (and to a lesser degree NA), aka MF59 or AS03, also enhance the biological mimicry to such a degree that the risk of GBS would again be dramatically increased? Since we (or at least I) don't know the relative potency of the endotoxin content of the 1976 vaccine possibly acting as adjuvant, as compared to MF59 or AS03, I don't believe we can give even a rough assessment, of the potential for GBS, before large scale vaccination happens, right?
Does that scare you? It does me. Not personally, but on a population level, the effect could be catastrophic. |
