Blaine Pfeifer, left, and Charles Jones (Onion Studio, University at Buffalo)
23 October 2017. Researchers from University at Buffalo and a campus spin-off enterprise devised a way to expand the scope of anti-bacterial vaccines, as shown in tests with lab animals. A team from the university’s engineering and medical schools, and the company Abcombi Biosciences Inc. in Buffalo, discusses its findings with a prototype vaccine against bacteria causing pneumonia in the 20 October issue of the journal Science Advances.
The researchers, led by bioengineering professor Blaine Pfeifer, are seeking more effective vaccines protecting against disease-causing bacteria that are often adept at evading current vaccine technologies. Current vaccines, note the authors, are designed to prevent bacteria from establishing colonies with biofilms in humans that let the microbes develop into disease-causing organisms. This approach, however, ignores the ability of some bacterial strains to cause disease later in their lifetimes, well after colonizing in their hosts, thus are not affected by many current vaccines.
Current vaccines, say the researchers bind, directly to the sugary polysaccharide coatings on the microbes’s surface. Each strain of the bacteria, however, has a slightly different coating, thus a different chemistry. This means a vaccine needs different proteins to bind to each of the different strains of the bacteria it seeks to address. The team chose the Streptococcus pneumoniae bacteria in this case, responsible for pneumococcal diseases including pneumonia, as well as ear, sinus, and blood stream infections. Current vaccines protecting against this microbe bind to 13 to 23 strains, while many more strains considered less dangerous are ignored.
Pfeifer and colleagues take a different approach to vaccine design, attacking the bacteria after they colonize and develop their disease-causing properties, as well as preventing establishment of colonies. This process, say the authors, allows a vaccine to cover many more strains responsible for disease, since it focuses on the common attributes causing disease. Their approach makes it possible to control other strains that may evade the initial attack and set up colonies.
The researchers use a technique called liposomal encapsulation of polysaccharides, or LEPS, that encases the sugars in tiny natural oil bubbles called liposomes. Storing polysaccharides in liposomes is simpler than synthesizing proteins that bind to these same sugars. When injected in the body, LEPS bubbles generate immune responses with antibodies that neutralize the bacterial strains they represent.
The team tested this process first in lab mice, and then rabbits. The researchers combined current anti-colonization methods against the known 13 and 23 strains covered by current vaccines, with LEPS bubbles containing other polysaccharides covering the vast majority of strains not addressed by current vaccines. On the surface of the LEPS bubbles, the researchers added 2 antigen proteins designed to alert the immune system.
Tests with mice show the vaccine prevents bacterial colonies from being established, as well as producing antibodies against 72 of the 95 non-colonizing strains. Tests with rabbits, more complex mammals than mice, show a similar presence of antibodies against the non-colonized strains in their blood. The researchers took the tests a step further, with simulated diseases in mice: pneumonia induced from influenza and sepsis. The results show the test vaccines protect the animals against these diseases, first by preventing colonies from being established, then generating antibodies against other strains that emerge after colonies are established.
Pfeifer and first-author Charles Jones founded Abcombi Biosciences in 2015 to license their vaccine technologies from the university and take them to market. Jones, now Abcombi’s CEO, notes in a university statement that their approach focuses only on disease-causing bacterial strains and leaves alone benign and beneficial bacteria. “Traditional vaccines completely remove bacteria from the body,” says Jones. “But we now know that bacteria — and in a larger sense, the microbiome — are beneficial to maintaining good health.”
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- Commercial-Scale Flu Vaccine Produced in Cell Cultures
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