<html><body style="word-wrap: break-word; -webkit-nbsp-mode: space; -webkit-line-break: after-white-space; "><br><div><blockquote type="cite"><div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; min-height: 14px; "><br></div> </div><span class="Apple-style-span" style="border-collapse: separate; color: rgb(0, 0, 0); font-family: Helvetica; font-size: 14px; font-style: normal; font-variant: normal; font-weight: normal; letter-spacing: normal; line-height: normal; orphans: 2; text-align: auto; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; -webkit-border-horizontal-spacing: 0px; -webkit-border-vertical-spacing: 0px; -webkit-text-decorations-in-effect: none; -webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0; "><div bgcolor="#ffffff"><div><font face="Calisto MT" size="2">Here is the second installment of this review, which looks at the role of endotoxins contained in vaccines either as contaminants or in the adjuvant material, and the potential synergistic effects of endotoxins, adjuvants, and HA in activity against nerve cells.</font></div><div><font face="Calisto MT" size="2"></font> </div><div><font face="Calisto MT" size="2">There is also an interesting discussion at the fluwiki link on this material, which is not included here. Also, you'll need to go to that link to access the charts and the other hotlinks.</font></div><div><font face="Calisto MT" size="2"></font> </div><div><font face="Calisto MT" size="2">Char</font></div><div><font face="Calisto MT" size="2">_______________________</font></div><div><font face="Calisto MT" size="2"></font> </div><div><font face="Calisto MT" size="2"><a href="http://www.newfluwiki2.com/diary/3625/guillainbarre-syndrome-after-influenza-vaccination-more-lessons-from-1976">http://www.newfluwiki2.com/diary/3625/guillainbarre-syndrome-after-influenza-vaccination-more-lessons-from-1976</a></font></div><div><font face="Calisto MT" size="2"></font> </div><div><table width="100%"><tbody><tr><td><h1 class="diaryTitle"><a class="diaryTitle" href="http://www.newfluwiki2.com/diary/3625/guillainbarre-syndrome-after-influenza-vaccination-more-lessons-from-1976"><font size="3">Guillain-Barre Syndrome after Influenza Vaccination - More Lessons from 1976</font></a><font size="3"></font></h1><h2 class="author"><font size="3">by:<span class="Apple-converted-space"> </span></font><a href="http://www.newfluwiki2.com/user/SusanC"><font size="3">SusanC</font></a></h2><h3 class="diaryTimestamp"><i><font size="3">Mon Jul 27, 2009 at 19:45:18 PM EDT</font></i></h3></td></tr><tr><td>A follow-up to<span class="Apple-converted-space"> </span><a href="http://www.newfluwiki2.com/diary/3126/swine-flu-1976-old-vaccines-new-lessons">Swine Flu 1976 - Old Vaccines, New Lessons?</a></td></tr><tr><td class="theFlip"><a href="http://www.newfluwiki2.com/userDiary.do?personId=5">SusanC</a><span class="Apple-converted-space"> </span>::<span class="Apple-converted-space"> </span><a href="http://www.newfluwiki2.com/showDiary.do?diaryId=3625">Guillain-Barre Syndrome after Influenza Vaccination - More Lessons from 1976</a></td></tr><tr><td>The 1976 vaccine was correlated with an increased incidence of GBS, which, according to a recent study<span class="Apple-converted-space"> </span><a href="http://www.newfluwiki2.com/diary/3126/swine-flu-1976-old-vaccines-new-lessons">described earlier</a>, may be due to<span class="Apple-converted-space"> </span><a href="http://en.wikipedia.org/wiki/Molecular_mimicry">molecular mimicry</a>, between the HA molecule and human gangliosides, proteins that permeate our nervous system.<p>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?</p></td></tr></tbody></table></div><div> </div><div>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<span class="Apple-converted-space"> </span><a href="http://jama.ama-assn.org/cgi/content/full/292/20/2478">Haber 2004, Guillain-Barré Syndrome Following Influenza Vaccination</a>)</div><div><p>As an extension of that,<span class="Apple-converted-space"> </span><b>can we also say that any HA that is similar to 1976 (like the current H1N1) may be more likely to induce GBS?</b><span class="Apple-converted-space"> </span> We can't answer that question, because we don't know what other components are/were important in the pathogenesis of GBS in 1976. </p><p>For example, it was widely believed that the 1976 vaccine had a particularly high<span class="Apple-converted-space"> </span><a href="http://en.wikipedia.org/wiki/Endotoxin#Lipopolysaccharide_and_other_endotoxins">endotoxin</a><span class="Apple-converted-space"> </span>content, a bacterial by-product (or impurity) of the vaccine manufacturing process, which may have contributed to the higher GBS rate. </p><p>One very interesting study<span class="Apple-converted-space"> </span><a href="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WCJ-48FSV9S-7&_user=3174088&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=3174088&md5=c6ca7ee8bc1c499d85ddafffe980a869">Geier 2003, Influenza vaccination and Guillain Barre syndrome</a><span class="Apple-converted-space"> </span>had the following findings:</p><div><br class="webkit-block-placeholder"></div><ol><li>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.<div><br class="webkit-block-placeholder"></div></li><li>Influenza vaccines contained from a 125- to a 1250-fold increase in endotoxin concentrations in comparison to an adult Td vaccine control<div><br class="webkit-block-placeholder"></div></li><li>Endotoxin concentrations varied up to 10-fold among different lots and manufacturers of influenza vaccines, as shown in the chart<p> <font face="Calisto MT" size="2">[see chart at above fluwiki link]</font></p><div><br class="webkit-block-placeholder"></div></li><li>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. </li></ol><p>Nevertheless, the authors still concluded that</p><blockquote>The biologic mechanism for GBS following influenza vaccine may involve the<span class="Apple-converted-space"> </span><b>synergistic effects of endotoxin and vaccine-induced autoimmunity.</b></blockquote><p>Here, the question gets interesting, because different kinds of bacterial endotoxins, eg from<span class="Apple-converted-space"> </span><i>E. coli</i>, have been used as vaccine adjuvants. The intranasal flu vaccine that<a href="http://www.newfluwiki2.com/showComment.do?commentId=133586">caused a spate of Bell's palsy cases</a><span class="Apple-converted-space"> </span>leading to its withdrawal, was<span class="Apple-converted-space"> </span><a href="http://content.nejm.org/cgi/content/full/350/9/896">adjuvanted with endotoxin from E. coli</a>. 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,<span class="Apple-converted-space"> </span><a href="http://www.ncbi.nlm.nih.gov/pubmed/18682690">Vaccine adjuvants: the dream becomes real</a>, "comes from the cell wall LPS (=lipopolysaccharide) of Gram-negative<span class="Apple-converted-space"> </span><i>Salmonella minnesota R59</i>5".</p><p>In other words, if endotoxin was a significant factor in vaccine-induced GBS in 1976,<span class="Apple-converted-space"> </span><b>the whole episode may have been a demonstration of the effect of a naturally-occuring adjuvant on induction of autoimmunity.</b></p><p>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.</p><p>If endotoxin was acting as an adjuvant and was partly responsible for the increased incidence of GBS in 1976,<span class="Apple-converted-space"> </span><b>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? </b>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?</p><p>Does that scare you? It does me. Not personally, but on a population level, the effect could be catastrophic.</p><p>__________</p><div><a name="134963"></a><b>btw, any correlation between</b></div><div>endotoxin concentration and rate of GBS being reported, is important for a specific and important reason - it can potentially demonstrate a<span class="Apple-converted-space"> </span><a href="http://en.wikipedia.org/wiki/Dose-response_relationship">dose-response relationship</a>, which according to this (and other)<span class="Apple-converted-space"> </span><a href="http://www.reliabilityoxford.co.uk/dose_response.html">product liability consultancy</a>,<span class="Apple-converted-space"> </span><b>is a fundamental requirement for making liability exposure assessment.</b><span class="Apple-converted-space"> </span><p>Which is a good example of the kind of issues that increasingly underlie major areas of scientific research...<br><font face="Calisto MT" size="2"></font></p><font face="Calisto MT" size="2"></font></div></div></div></span></blockquote></div><br><div apple-content-edited="true"> <span class="Apple-style-span" style="border-collapse: separate; color: rgb(0, 0, 0); font-family: Helvetica; font-size: 14px; font-style: normal; font-variant: normal; font-weight: normal; letter-spacing: normal; line-height: normal; orphans: 2; text-align: auto; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; -webkit-border-horizontal-spacing: 0px; -webkit-border-vertical-spacing: 0px; -webkit-text-decorations-in-effect: none; -webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0; "><div style="word-wrap: break-word; -webkit-nbsp-mode: space; -webkit-line-break: after-white-space; "><span class="Apple-style-span" style="border-collapse: separate; color: rgb(0, 0, 0); font-family: Helvetica; font-size: 14px; font-style: normal; font-variant: normal; font-weight: normal; letter-spacing: normal; line-height: normal; orphans: 2; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; -webkit-border-horizontal-spacing: 0px; -webkit-border-vertical-spacing: 0px; -webkit-text-decorations-in-effect: none; -webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; "><div style="word-wrap: break-word; -webkit-nbsp-mode: space; -webkit-line-break: after-white-space; "><div><div><div>Kris Knight of WellAware Life Enhancement Center</div><div>Phone: 1-608-ALL-LIFE</div><div><a href="mailto:welaware@merr.com">welaware@merr.com</a></div><div><br></div></div><br></div><br></div></span><br class="Apple-interchange-newline"></div></span><br class="Apple-interchange-newline"> </div><br></body></html>