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CPGR Using Peptide Arrays to ID Antibodies for Use in Influenza Biomarker Panel

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This story originally ran on June 24.

By Adam Bonislawski

South Africa's Centre for Proteomic and Genomic Research is developing high-density arrays of synthetic peptides in an effort to identify influenza antibodies that could serve as a biomarker panel for vaccine development.

In a project announced last week, CPGR is collaborating with scientists from the University of British Columbia to build a biomarker signature that could be used in the development of seasonal influenza vaccines.

CPGR will be developing multiplex protein array-based antibody profiling assays and related bioinformatic analysis methods for the project using samples provided by the UBC team, which is led by Tobias Kollmann, assistant professor in the university's division of infectious and immunological diseases in the department of pediatrics (PM 6/18/2010).

According to information from the World Health Organization, seasonal influenza annually results in about three to five million cases of severe illness, and about 250,000 to 500,000 deaths worldwide.

"It's a huge pandemic problem that recurs every year and there are ongoing vaccination programs out there," Reinhard Hiller, managing director of the CPGR told ProteoMonitor, explaining why season influenza is a good fit for the study. He added that the CPGR/UBC project is the first study he is aware of to use biomarkers as development tools for a vaccination program.

The CPGR and UBC groups are looking to identify human antibodies expressed in response to exposure to influenza antigens. To identify these antibodies, CPGR researchers are creating high-density arrays of synthetic peptides designed to match the epitopes of selected proteins of various influenza strains. These arrays will then be used to detect antibodies in serum samples from 200 influenza patients provided by UBC.

The study will look at several thousand peptides, with the goal being to identify 20 to 30 antibodies that could be used as biomarkers, Hiller said.

"Initially it's a very broad-based screening approach to identify antibody binding patterns to epitopes of antigens that are derived from various strains of influenza and then to narrow it down, ideally, to be a predictive signature or antibody profile that can add value to future vaccination programs and clinical trials," he said.

Such a signature could aid the development and administration of the vaccine in a variety of ways. The profile will in theory enable researchers to distinguish between subjects who are showing antibodies to influenza and those who are not. This will allow for better stratification of patient cohorts in clinical trials, helping researchers weed out subjects who are already showing antibody titers similar to what trial sponsors would hope to build through vaccination.

It could also be useful in distinguishing responders from non-responders to a given formulation of a vaccine and could possibly be used to determine whether a given patient needs to receive the vaccine at all, Hiller said.

"If someone has the protective antibodies, then there would be no need to vaccinate," he said. "There is potentially a cost saving component for healthcare providers and reimbursement organizations to be able to say, 'Well, can you please test the subject in advance to determine whether or not they should be vaccinated at all?'"

CPGR has just signed a contract with UBC for the project and is currently awaiting patient samples, Hiller said. He expects that CPGR's portion of the project will be done in roughly three months.

"We've been using these tools in the past, so we've developed the assays and we've established proper bioinformatic pipelines to make sure that from a high-density peptide array we can extract good quality raw data and then convert this raw data into meaningful results using statistical and bioinformatic analysis," Hiller said.

Founded in 2006 as part of an initiative by the South African government, CPGR aims to support the development of the country's biotech industry by providing scientists with infrastructure for research into genomics, transcriptomics, proteomics, and bioinformatics and by establishing a track record of successful R&D in areas like biomarkers and drug development.

The organization is interested in using the methods developed for the seasonal influenza project to create biomarker panels for other vaccines, Hiller said, although he declined to specify what diseases it might target, saying only "other infectious diseases quite broadly."

Depending on what sort of protein biomarker panel the CPGR is able to put together for influenza, there are a variety of ways it may apply the research going forward, Hiller said.

"There are a variety of options here. We could apply [the research] to other disease areas and just carry on what we started in one disease area and diversify into other areas," he said.

"At the same time we could take the biomarker panel that we generated and take through verification and validation to a validated biomarker panel that could be transferred onto a Luminex platform, for example, to make it more amenable to higher throughput and standardized determination of biomarkers in labs all over the world," he added.

"It's also going to be a question of where the biomarker test is going to be positioned in the value chain," he said. "Is it more about a sort of companion diagnostic for clinical trials? Or is it going to be something located in clinics, sort of point-of-care type testing?"

Hiller declined to provide the exact terms of the collaboration, but he did say that UBC was paying the CPGR for its work on the project. CPGR also has an option to license any intellectual property generated during the contract research agreement, he noted.

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