Saturday 27 April 2013

A vaccine for autism symptoms? Not exactly

"Vaccine". "Autism".

I'm struggling to think of two words in combination which, in modern times, are any more likely to stir up emotion, debate and even argument. Indeed in these times of measles outbreaks and seemingly daily news reporting on the very, very strong requirement for vaccination to protect against the disease, it is coincidental that two research papers should now land in my inbox which mention both of those words in the title.
Paradise in Zakynthos @ Wikipedia  

The first paper is by Ivan Gentile and colleagues* reporting on seropositivity rates to measles, mumps and rubella in cases of autism spectrum disorder (ASD) following MMR vaccination. The second paper, by Brittany Pequegnat and colleagues**, discusses the concept and early development of a vaccine targeting a specific type of gut bacteria which the authors speculate might have some interesting knock-on effects to some of the signs and symptoms linked to cases of autism.

Although pertinent to the current measles news, I'm not on this occasions heading too far into the Gentile paper. My reasoning is two-fold: (i) the paper is fairly explanatory in that "children with ASD have a similar level and seropositivity rate of antibodies against the MMR vaccine to same-age controls" (bearing in mind the small participant numbers) and, (ii) I'm not really qualified to go into any heavy duty discussions on how this fits into the existing scientific literature on this topic; bearing in mind a similar finding previously published*** and a contrary one****. All I will say is that vaccination saves lives as per this CDC flier.

The Pequegnat paper has received some media attention with headlines like: "Vaccine To Help Autism Symptoms Developed" and "Scientists develop first vaccine to help control autism symptoms". As one might expect, headlines which don't necessarily reflect the actual science reported so far...

The long-and-short of the research is that based on some earlier findings of a specific gut bacterium being discovered in a group of children with autism***** - Clostridium bolteae previously called Clostridium clostridioforme (see here******) but renamed, I think, after Ellen Bolte******* - the authors applied some established know-how to begin formulating a vaccine targeting the surface sugars, polysaccharides, of C.bolteae. If you want to see the human face of the researchers involved, look no further than this article from 2012.

All that talk of this research helping to 'control' autism symptoms is, at the moment, more speculation than fact. As far as I can see, the authors got no further than providing the "first description of a C.bolteae immunogen" following some initial investigation in rabbits. It is therefore a significant jump to say that this vaccine will affect the behavioural presentation of autism. Indeed, no-one really knows if it will impact on any gastrointestinal (GI) symptoms either.

That being said, I am quite interested in their report and the concept that we could artificially stimulate immunity to 'undesirables' such as specific types of gut bacteria. As well as being particularly interested in all things bacteria on this blog (see here and here), a quick trawl of the scientific literature suggests that the future is now as per the paper by Sougioultzis and colleagues******** (open-access) on a C.diff toxoid vaccine. One wonders whether we might also apply similar logic to other bacterial findings related to autism such as that very interesting Sutterella work?

I am also drawn to the polysaccharide bit of the Pequegnat paper and whether or not it is useful to link back to the work of Harumi Jyonouchi and colleagues on the presence of specific polysaccharide antibody deficiency (SPAD) comorbid to some cases of autism. If I am interpreting this correctly, the suggestion is that SPAD interferes with correct antibody formation to polysaccharide coated bacteria which could have implications I assume, for vaccination to/against bacteria like C.bolteae also. I could be wrong though.

I'm gonna stop with this post shortly. There are other things I could say, for example, discussing the method of vaccine delivery (nanoparticle anyone?) including doing away with the big scary needle in favour of something a little more 'ouchless' (microneedles or even inhaled delivery). But that is perhaps fodder for another day.

Oh, and just so you know, on purpose I posted a lovely serene picture from the beautiful island of Zakynthos instead of one of those pictures of big needles complete with crying child which, as other commentators have pointed out, might not necessarily be the best platform on which to discuss the topic of vaccination.


* Gentile I. et al. Response to Measles-Mumps-Rubella vaccine in children with autism spectrum disorders. In Vivo. 2013; 27: 377-382.

** Pequegnat B. et al. A vaccine and diagnostic target for Clostridium bolteae, an autism-associated bacterium. Vaccine. April 2013.

*** Baird G. et al. Measles vaccination and antibody response in autism spectrum disorders. Arch Dis Child. 2008; 93: 832-837.

**** Singh VK. et al. Abnormal measles-mumps-rubella antibodies and CNS autoimmunity in children with autism. J Biomed Sci. 2002; 9: 359-364.

***** Finegold SM. et al. Gastrointestinal microflora studies in late-onset autism. Clin Infect Dis. 2002; 35 (Supplement 1): S6-S16.

****** Song Y. et al. Real-time PCR quantitation of Clostridia in feces of autistic children. Appl. Environ. Microbiol. 2004; 70: 6459-6465.

******* Bolte ER. Autism and Clostridium tetani. Med Hypotheses. 1998; 51: 133-144.

******** Sougioultzis S. et al. Clostridium difficile toxoid vaccine in recurrent C. difficile–associated diarrhea. Gastroenterology 2005; 128: 764–770.

---------- Pequegnat B, Sagermann M, Valliani M, Toh M, Chow H, Allen-Vercoe E, & Monteiro MA (2013). A vaccine and diagnostic target for Clostridium bolteae, an autism-associated bacterium. Vaccine PMID: 23602537

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