Diagnostics & Imaging Week
Founded within the last month and based on technology aimed at predicting future epidemics, Replikins (Boston) has developed a software program for calculating the spread of influenza strains and is preparing to launch animal studies involving the first of its synthetic vaccines targeting the flu.
Work at the start-up firm focuses on its namesake, replikins, viral peptides that can be measured by their rate of replication to determine the potential of specific virus strains becoming global epidemics.
Although virus replication has been studied for 50-plus years, it's only recently that researchers have discovered the replikins, said company founder Samuel Bogoch, a former faculty member of Harvard and Boston University School of Medicine.
He said the find was "based upon the recognition of a chemical change, or peptide change, that occurs with rapid replication," and the ability to track those changes.
Flu viruses were the first to be studied with the method, mostly because researchers were able to access epidemiological data from the Centers for Disease Control and Prevention (Atlanta) going back almost 100 years. Using Replikins FluForecast computer program, the company was able to analyze peptide sequences from those strains, which included the strain of H1N1 subtype that caused the Spanish flu pandemic of 1918. Analysis revealed that, prior to the outbreak, there was a strain-specific increase in replikin count.
"We had a chance to compare the absolute levels of the peptides in quantitative amounts to the occurrence of epidemics," Bogoch told Diagnostics & Imaging Week's sister publication BioWorld Today, "and we were pretty surprised to find that there's a point-to-point correlation between the high points of the epidemics" and high replikin counts.
The FluForecast program is designed to measure the peptide changes, which typically occur a year to three years before the epidemic itself, Bogoch said.
For example, the outbreak of severe acute respiratory syndrome (SARS) caused by a coronavirus, which appeared for the first time in 2003, could have been predicted using the technology, he said.
Because SARS had no data history, the company was not able to track the specific virus, but a look at the whole coronavirus group showed that the replikin count "stayed quite low in the dormancy area of 1 to 2 replikins per 100 amino acids" for several years before 2002 when it suddenly increased by three or four times that level, Bogoch said. "Then, in 2003, out pops the SARS epidemic."
The count fell again, and no case of SARS has been reported since 2003.
It's like a "factory" that is the busiest "before the product is released," Bogoch said, "which is good, because it gives us an opportunity we haven't had before to see in advance of what's coming and to see it in quantitative terms."
The discovery is made even more poignant by the threat of a potential avian flu pandemic. Bogoch said the technology was able to predict three of the avian flu epidemics since they first emerged in Hong Kong in 1996-1997. Following early reports, Hong Kong officials were meticulous about destroying birds that could carry the virus, and the replikin count fell to normal levels in 1997, ending the threat, for a little while.
"They declared victory, but our replikin count said that it was back up again [in] 2002 and 2003," Bogoch said, adding that the count rose again before the virus emerged in Vietnam in 2004 and "since then, the replikin count has stayed up and hasn't gone down yet."
As far as whether this could signal a future pandemic, Bogoch said "we do not have any clue this is about to end."
Replikins was formed around the program, but predicting a potential pandemic is only the first step. In addition to counting replikins, the FluForecast technology also records which of the structures are most prevalent in any given strain, providing researchers with a specific target at which to aim a vaccine.
"So instead of going blind, you have a target [on which] to build your vaccine," Bogoch said.
He added that the company also works with synthetic vaccines to avoid the chance for protein contamination that comes from using part or all of the actual virus to synthesize a treatment. One of the most notable instances of contamination occurred in 1976, when people were "rushing to get inoculated for the swine flu epidemic," before the vaccination program was cancelled after 25 deaths and a rise in Guillain-Barre syndrome were linked to the vaccine, he said.
With a synthetic vaccine that's targeted to specific amino acids, "we have a better chance of knocking out the organism, and there are no contaminants," Bogoch said.
At this time, the company is "about halfway there," he added. "We know the [vaccine] works to make antibodies, but the question is does it protect against [the virus]?"
To answer that question, Replikins is preparing to begin preclinical trials in several countries to test the vaccine technology in animals. If the results are promising, the vaccines could enter the clinic in the next six to 12 months.
The company's FluForecast also could help government's predict which seasonal flu strain is most likely to hit in the coming years to make sure vaccine stockpiles include the most effective vaccines.
Beyond influenza, Replikins anticipates using its program for measuring rapid replication to address other infectious diseases such as AIDS, foot-and-mouth disease, and malaria.
The company recently completed its first financing, which Bogoch described as "very generous." It has a "handful" of employees, with expectations of hiring additional staff to set up labs in areas outside the U.S.
"We'll be very busy in the coming year," Bogoch said, "testing as many of these diseases as possible to see if we get good antibody responses to our vaccines based on the replikin structure."