Timelines for finding a vaccine against the fast-spreading Zika virus are vastly overstated, Samuel Bogoch, founder and chairman of Replikins Ltd., told BioWorld Today. "Everybody is saying it might take three, four, even 10 years to get [a candidate]," he said. "We have one now." Scientists at Replikins, of Boston, are "just making [the vaccine] synthetically," after formulating it a couple of weeks ago, a process that took about seven days, he said. The candidate is being shipped in freeze-dried form to a testing facility.
Zika, meanwhile, is "spreading explosively" in the Americas, the World Health Organization's (WHO) director-general, Margaret Chan, said in a briefing to the executive board, and the "level of alarm is extremely high."
Isolated in 1947 in a monkey in Uganda, the mosquito-spread ailment crept into other territories and lately has blown up. About Zika, which most people can overcome but which has been linked to serious brain birth defects in the offspring of infected mothers, Chan said WHO is "deeply concerned." Plymouth Meeting, Pa.-based Inovio Pharmaceuticals Inc. and Geneone Life Science Inc., of Seoul, South Korea, this month joined forces to come up with a vaccine. (See BioWorld Today, Jan. 25. 2016.)
Replikins, for its part, has in the works a synthetic genomic-based peptide vaccine-blocker for Zika based on a predictive and potentially therapeutic technology that, Bogoch said, has been used in the 2014 Ebola outbreak, the severe acute respiratory syndrome (SARS) scare of 2003, H5N1 in 2006-2007, and the H1N1 pandemic of 2009. "We measure a structure in the gene of the virus," he said. "We found in around 2000 that, when glioblastoma cells were dividing more rapidly in tissue culture, a change occurred in the gene that we could measure." That was the concentration of substances dubbed replikins, which are defined by the concentration of lysine and histidine residues and the spacing between them. "They had not been described before, or since," he said. (See BioWorld Today, April 27, 2006.)
The company went searching for more, and established as a gauge the replikin count: the number of structures per 100 amino acids in the gene. "When the virus is resting quietly, not doing much, the count is less than one," Bogoch said. "There's always something, because it has to divide. It's less than one, and up to four." Infectious disease breakout mode is characterized by a count of more than four. With H1N1, "we tracked it as it went from three to four-point-something, to six, seven, eight," he said. "Then we blew the whistle," and published the data in April 2008. "Exactly a year later, the announcement was made that we had something that looked like a pandemic and by June it was called a pandemic." (See BioWorld Today, May 26, 2009.)
Continuing to explore the "pretty strong coincidence," Bogoch said, the firm came to realize that the groundwork actually had been laid in 2002 with SARS. Scientists measured a threefold increase in replikin count that year, and in 2003, SARS broke out. "That was really the first one we did, but we didn't understand it," he said. "We've done over 3 million gene sequence analyses since then for 16 different viruses in 41 outbreaks. All of them, so far we're waiting for the first one to prove that we're wrong show a marked increase in the replikin count one to two years before the outbreak." As forecasters, "we're [all] real dumb cookies," he said. He also referred to "perennial virgins" and "sitting ducks. Every time we get hit, it's a big surprise." But it's nobody's fault, he said. "We had nothing to measure before."
Working up a prospect for Zika, Bogoch said, "only took about an hour, because we only had 170-odd samples in Pubmed, our major source of gene sequences. Fortunately, we've been publishing these faithfully, not knowing what to do with them, for a couple of decades. We found that, first of all, the replikin counts were in a range where they'd never been before, even in 1947. The suspicion voiced by several of my colleagues that this thing came so suddenly there must have been some change in the gene is supported by our data." The company, he said, found "a bunch of replikins that simply were not there before."
The Zika vaccine "could be a total flop, but at least we're doing it now, not 10 years from now," Bogoch said. A potential vaccine by Replikins for Middle East respiratory syndrome (MERS) recently produced antibodies after five weeks. "The National Institutes of Health [NIH] came up with exactly the same results in August with their MERS vaccine, saying, 'This damn thing takes five to six weeks to form a decent antibody,'" he noted. "So that's, at the moment, a question mark, but [the vaccine] does form an antibody and we do therefore have a potential candidate vaccine."
His firm "did exactly the same thing for Ebola," Bogoch said. With the latter, replikin counts increased 20 times in 2012 and 2013, and the outbreak happened in 2014. "In August 2014, we were doing the daily follow-up for the replikin counts," he recalled. "During that period, the counts kept going up, and then suddenly they went down, from 20 to 0.5. We were just about to publish the thing [about the counts] going up in 2012 and 2013, and we said, 'Wait a minute, there's something wrong here.' It went down and stayed down. In October, we got the nerve to publish and we said, '[The outbreak] is all over, folks.' You can imagine how that was received. The week before our publication, the NIH, the Centers for Disease Control, and everybody was calculating we'd have 1.25 million cases by January. You've either got to be suicidal academically or very sure of yourself to [publish against the grain]. We were only a little bit sure of ourselves, not very, but we felt we had an obligation to do it, just in case."
Lessons learned in replikins and Ebola could help in the future. "Think of all the army we would have saved going over and building the buildings and stuff like that," he said. "A couple of billion dollars were spent during that fiasco. And it stopped, and now everybody is taking credit, saying it's because we built all those things. Balls! It was over. The genes said it was over." But the publication "was totally ignored," he said. "More people are looking now. It takes a woman about to have a microcephalic child to wake up some people."
With the potential Zika vaccine, "the worst [scenario] is that it does nothing," Bogoch said. "Or it has a little effect, and we have to figure out what to do to make it better. Or it works fine. All those are possible. We won't know for another five to six weeks." A factor in Zika "that's so nasty is that in 80 percent of [cases], apparently there are not enough symptoms to clue you," a factor that's overlooked by some reports, he said. "Then they deliver a child eight or nine months later with a small brain. That is what's scary. There's something awful about not knowing you've got this virus and it's destroying the brain of your growing fetus. But eventually, if you have a decent vaccine, everybody will get it before they get pregnant. There's no reason you can't get immunity to Zika."
How soon the vaccine, if it works, might reach humans "depends on attitudes, politics, all kinds of things," Bogoch said.
In Brazil, where the virus is especially virulent, officials are "certainly going to work up a trial in humans," he said. "Not pregnant ladies first, but maybe in females and males to see whether you get the immune response. That would only take another four or five weeks, if they got to it. Then they could focus on large-scale trials in people who are about to become pregnant give them a month or two to develop their immune response and then let them go get pregnant. We're a long distance, i.e., a month or two away from that, but not a year or two or 10 years."
The world "has to start thinking pre-outbreak," Bogoch said. "We don't wait for a fire to break out to try and [then] figure out what kind of fire department we should organize. There should be a 'virus department,' and it should be functioning every day in every civilized and uncivilized spot. They should be going out checking contacts in high-risk areas for a particular virus. They should be taking samples and having central labs doing these sequences. It's not hard to do, and it's not even expensive now. It should be done routinely and on the basis of those sequences, if they start building up their replikins, you better start making a vaccine and testing it," he said, a strategy that "costs a lot less than the billions that are being thrown every time" a disease breaks out.
"You might not be able to catch them all, but you could certainly catch a recurrence of Ebola. There have been a whole bunch of little outbreaks since 1976. We've been working with people who said, 'Oh god, we get those every couple of years. That's nothing.' And then all of a sudden it was something," he noted.
Asked whether he had a hunch about the efficacy of the Zika candidate, based on findings so far, Bogoch stayed wary. "We don't have a hunch," he said. "We have a hope."