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admin | Herbal Remedies For Bv | 23.02.2015
Last year, following the publication of his latest research in the journal Vaccine, dozens of emails flooded polysaccharide chemist Mario Monteiro’s inbox.
Mario Monteiro holds a model of one of the structural key markers of Campylobacter polysaccharides, a rare sugar called 6-deoxy-heptose. In the past decade, researchers have focused on a possible connection between the high bacterial loads found in the gastrointestinal tract of autistic children and their neural development disorders, a link commonly called the ‘gut-brain’ balance. This molecular model of a prototype polysaccharide vaccine­ against Campylobacter jejuni, one of the causes of traveller’s diarrhea, shows its helical conformation.
Although Monteiro is not an autism expert, he is in an excellent position to develop a vaccine against autism-linked pathogens. Upon completion of his PhD, Monteiro was snapped up by, first, the National Research Council’s (NRC) Canadian Bacterial Diseases Network in Ottawa and later Wyeth Pharmaceuticals in the United States. Polysaccharide vaccine research has roots in the early 20th century, when American immunologists Michael Heidelberger and Oswald Avery discovered that Streptococcus pneumoniae polysaccharides act as antigens, which spark an immune response in the body just as proteins do.
Further advances in the field were stymied when Scottish Nobel laureate Alexander Fleming discovered penicillin a few years later, allowing many bacteria to be treated by antibiotics rather than vaccines. One of Monteiro’s goals is to overcome the need for frequent booster shots by making the antibodies raised against polysaccharides last longer. Another reason polysaccharide vaccine research languished for so long was the inherent complexity of the molecules. Vaccine development is a long process, taking anywhere from 10 to 30 years to bring to market.
Monteiro’s unique approach to anti-diarrheal vaccine development began, he says, with “a vision. His latest challenge may be his biggest yet — creating a vaccine to fight the gastric bugs that cause havoc in the lives of autistic children.
Monteiro’s paper, about a potential vaccine for gastrointestinal bacterial infection in autism spectrum children, struck a chord with parents, who cope daily with their youngster’s chronic constipation and diarrhea, self-destructive behaviours and cognitive and social delays. Different types of Campylobacter express­ polysaccharides with their own characteristic 6-deoxy-heptose.


So far, the main culprits include microbes from Clostridia, Desulfovibrio and Sutterella species. During his PhD studies in the early 1990s, Monteiro, a Portuguese native, delved into the study of bacterial polysaccharides, the long, sugar-based polymers that cocoon bacteria in little carbohydrate ‘jackets.’ Conventional vaccines work by injecting the inactivated pathogen or their proteins into the bloodstream, triggering the development of antibodies. Wyeth (now part of Pfizer) wanted Monteiro’s polysaccharide expertise to develop a vaccine against H. Unfortunately, the antibodies spawned by T-cell independent polysaccharides generally don’t last as long as those raised against T-cell dependent proteins, in that polysaccharides raise mostly short-lived IgM antibodies while charged proteins generate long-lived IgG antibodies. It took half a century for polysaccharide vaccine research to be revived; among the first success stories was a pneumococcal vaccine developed for adults, partially based on structural work by Monteiro’s mentor, the late Malcolm Perry of the NRC. A popular approach is called the “conjugation technique,” which links the polysaccharide molecule to a protein carrier molecule. Although bacteria are primitive and have inhabited the earth far longer than mammals or even plants, their carbohydrate structures “are a million times more complex,” says Monteiro.
You have to ask yourself, ‘what diseases are really important that we have to save people from? Asian countries,[18] United States (including Hawaii), Canada ,[19] and Scotland)[20] due to bacterial resistance.
Polysaccharide vaccines operate the same way but they use a different class of target molecules, allowing researchers to go after organisms for which the conventional approach has failed. The elderly are especially susceptible to Streptococcus pneumoniae, which causes pneumonia, meningitis and septicemia.
Navy microbiologists supplied Monteiro with the bacteria he needed to work with and undertook the pre-clinical trials. Researchers are aware that about 90 percent of autistic kids have severe gastrointestinal upsets while 75 percent of those have chronic diarrhea, forcing them to remain diapered at an age when other youngsters are mastering their ABCs at school. For his graduate studies, Monteiro focused on the polysaccharides of Helicobacter pylori (H. Protein-based vaccines with their peptide backbone — while relatively easy to produce and construct — are capricious.


The intellectual property for the vaccine is being shared equally between the navy and the University of Guelph, Monteiro says. Monteiro says that some studies suggest that metabolites released by these bacteria, such as hydrogen sulphide and propionic acid, not only irritate the gut but may also indirectly affect the brain at a young age.
When protein is removed from a bacterial cell and purified to make the vaccine, they sometimes lose their functional shape.
Studies show that mice, for example, exhibit autism-type behavior when injected with propionic acid, Monteiro says. This means that they have low immunogenicity — antibodies will not recognize the live invader due to this difference. Such studies have helped strengthen the ‘gut-brain’ theory, for when autistic children in a study were put on a regimen of strong antibiotics, not only did the gastrointestinal problems disappear but so did many of the bewildering behaviors. Polysaccharides, however, keep their main conformation when removed from a bacterium, giving them high immunogenicity, says Monteiro.
Unfortunately the pathogen is unharmed; the patient survives the infection, but can become an asymptomatic C.
Because the molecules are repeating blocks of oligosaccharides, antibodies recognize many parts of the polysaccharide.
The vaccine that Monteiro developed triggers an attack against the bacteria’s surface polysaccharide antigens.
Phase 1 human trials — funded by the American National Institute of Health and the US Navy — are poised to begin shortly to test the efficacy of the C.



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