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Paving the Way Towards Universal Protection
CHORI Scientists Participate in Collaboration to Characterize Candidate Protein for Pneumococcal Vaccines or Drug Targets

In a new study by CHORI scientist Mark J. Jedrzejas, PhD, and his colleagues Daniela Bumbaca, BS, and Daniel J. Rigden, PhD, published in the February issue of Proteins, the Jedrzejas lab reports on the genome-based identification and characterization of a possible candidate gene in the development of vaccines and/or antibiotics against Streptococcus pneumoniae (S. pneumoniae), the pathogen that causes pneumonia, ear infections, and meningitis.

The study confirmed Dr. Jedrzejas and his colleagues' genome-based predictions that the protein, coded by open reading frame SP 1492 and named MucB, is a surface-exposed protein expressed by S. pneumoniae that binds with mucin.

"The most significant aspect of our study is that our methods of exploring the genomic sequences were correct, and in all cases, our predictions were accurate," says Dr. Jedrzejas. "We're showing that genomic information can be used to successfully identify these kinds of characteristics."

Currently, there are some vaccination options to fight S. pneumoniae, which include a more traditional polysaccharide-based vaccine for older children and adults and a newer, conjugate vaccine for children 2 years and younger. The traditional vaccine is only effective in approximately 60 percent of the population, however, while the conjugate vaccine also has some limitations.

"The conjugate vaccine works right now, but it's made from a carbohydrate plus a protein that is from a generic toxin, not from S. pneumoniae," explains Dr. Jedrzejas.

This means that the vaccine only provides protection against the strains in the vaccine, rather than universally protecting against all known strains, as well as potential new strains.

As Dr. Jedrzejas points out, "Just as you have antibiotic resistance, you have new strains of bacteria. If the current vaccine doesn't protect against a new strain, it will spread and could be a very serious issue. One can't be short sighted."

The candidate protein characterized in the latest publication, however, could be a critical player in the development of a more universal vaccine or novel antibiotic, due to the specific properties which the Jedrzejas lab was able to identify with genomic sequencing, and then confirm in the latest publication. One of these properties is that MucB is one of but a few proteins identified that also binds to the mucosa that generally lines the nasal and airway passages.

This unique property of MucB suggests that it could be an ideal candidate for the development of mucin-blocking drugs that could compromise the ability of S. pneumoniae to bind to human tissues.

"This particular protein holds a lot of promise," says Dr. Jedrzejas. "In addition to its adhesion properties, it was also highly immunogenic in our mice studies - which is exactly what you want in a vaccine candidate, something to make lots of antibodies."

Yet it is only through the long and painstaking process of basic research that proteins like MucB and their characteristics can be identified.

As Dr. Jedrzejas says, "This kind of research, you just start from scratch. You say, let's look at this genome and see what comes up. We found hundreds of things, and then we had to choose what we thought was important to follow-through on. In this case, what we chose actually turned out to be what we thought it would. You don't expect things to work out that way very often."

With the combined efforts of the collaborative team in the Jedrzejas lab, their predictions did prove to be accurate on all fronts, paving the way for more exploratory research into the possibilities that MucB holds for eliminating once and for all the life-threatening infections caused by S. pneumoniae.

"The next step is obtaining the three-dimensional structure," says Dr. Jedrzejas. "Once we determine the structure, we can design a theory of how the protein interacts with mucin, how it really works. Once we know that, we can presumably use that information to fight the disease."


Monday, May 16, 2011 11:33 PM

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