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Emerging virus speed brings science, business challenges for vaccine development

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By Anette Breindl
Science Editor

Last Friday, the Centers for Disease Control and Prevention (CDC) announced the first U.S. case of Middle Eastern respiratory syndrome coronavirus (MERS-CoV) infection. The patient had returned from Saudi Arabia on April 24, first fell ill in Indiana on April 27 and was hospitalized on April 28.

A week earlier, the Saudi king fired his health minister amidst a surge of MERS-CoV cases in Saudi Arabia, the country where the virus first surfaced in 2012, and which has had the biggest caseload to date. (See BioWorld Today, March 25, 2013.)

On Monday, according to local news reports, Indiana state health officials said the U.S. patient was "improving," and so far, with about 75 percent of his contacts on the plane and bus he used to travel home contacted, no new cases have surfaced.

Both the Saudi Arabian uptick and the first U.S. case thrust MERS into the spotlight and, inevitably, led to comparisons with severe acute respiratory syndrome coronavirus (SARS-CoV), which killed 774 and sickened thousands more in 2002 and 2003, rapidly jumping from mainland China to Hong Kong to Canada, as well as other Asian countries and the U.S., before being contained by public health measures.

The fact that SARS-CoV was contained by public health measures, rather than any vaccines or treatments, highlights a sobering fact about emerging viruses, namely that doing any sort of drug or vaccine development for them is a form of Pascal's wager. If a virus does become widespread, it is both a global public health problem and a huge market.

But vaccines are particular to viruses. Which particular virus, let alone which viral strain, might attain such status is impossible to predict precisely – and once a virus does flare up, its timeline is such that developing a vaccine against it in time is a daunting task.

Such development is possible, Gale Smith, who is vice president of vaccine development at Novavax Inc., told BioWorld Today. He cited work the company did last year on a vaccine for the H7N9 influenza strain, which is one of several avian influenza strains that have high pandemic potential.

A first wave of H7N9 cases occurred last March. Novavax began testing a vaccine it developed with its VLP technology in May, initiated a phase I trial in July, and reported results from that trial, which demonstrated safety and immunogenicity of the vaccine, in the New England Journal of Medicine in November 2013.

Still, the relative timelines of vaccine development and outbreaks of emerging viruses means that "the business model for these kinds of opportunities is based on government contracts and government demand," through mechanisms such as both outright research funding and option purchases, Barclay "Buck" Phillips told BioWorld Today.

Phillips is senior vice president and chief financial officer at Novavax, which is developing a vaccine candidate for MERS-CoV. The company published preclinical data in Vaccine in April showing that its experimental vaccine blocked MERS-CoV infection in animal models.

Pandemic flu viruses typically follow a pattern of a smaller outbreak, followed by a lull, followed by a second, larger outbreak, which means that vaccine makers have six to nine months to develop a vaccine candidate and demonstrate its immunogenicity. And coronaviruses follow a somewhat similar pattern – the current rise in cases in Saudi Arabia may be the beginning of such a second wave – which makes rapid development of vaccines against them feasible in principle.

"When the [MERS] sequence was published, we didn't need anything else to begin production of a vaccine," Smith said. "We optimize it for production, but we don't change the amino acid sequence."

In the fight against SARS, however, vaccines did not end up playing a role. Four such vaccines were tested in phase I trials, but the virus came and went so quickly that none of them progressed into later-stage trials.

At this point, the University of Maryland's Matthew Frieman told BioWorld Today, "I really don't think SARS is going to come back."

Frieman, who is at the University of Maryland, is the corresponding author of the April Vaccine paper showing that Novavax's approach could induce high antibody titers and were able to block MERS infection in animals. The paper also contained data showing that the company's approach was able to induce an antibody response to SARS.

Frieman said that his continuing interest in SARS is due to the broad lessons the virus offers about respiratory viruses, and even more broadly, about lung damage.

The immune response to both SARS and other respiratory viruses, right back to the 1918/1919 "Spanish flu," can be as much of a problem as the infection itself. (See BioWorld Today, Jan. 18, 2007.)

And, Frieman said, "whether it's SARS or flu or asbestos or nanoparticles, the response is always the same in the lung."

SARS also remains interesting because it was the first deadly coronavirus – or at least, the first one that was identified as deadly. Frieman said one possibility is that other coronaviruses, or even SARS itself, have long caused "blips of undiagnosed respiratory disease" that are now being identified because the sequencing technology is there to do so.

But whether coronaviruses are truly a new problem or merely an old problem that has been newly identified, "if you've got a [coronavirus] like SARS, and then another one like MERS a few years later, it suggests that these are going to be important in the future" in terms of their impact on public health, Barney Graham told BioWorld Today.

Graham is the chief of the viral pathogenesis section of the NIAID's Vaccine Research Laboratory (VRL), and he worked on a SARS vaccine after the virus made its appearance as a public health threat.

As a government entity, Graham said, the VRL can take a broader view – he described his goal as "in a sense, to develop a periodic table of viruses" as well as platform technologies.

In a best-case scenario, such an approach could ultimately lead to something of a Lego-like approach to vaccine development. It does, however, require an ability to take the long view in the first place – an ability that is hard for companies putting out quarterly reports to their investors.

"It's a very difficult calculation companies have to make, because if they go out of business it doesn't help anyone," Graham said.

But if they are not quite developing a periodic table of viruses, companies such as Novavax, too, learn broader lessons from viruses such as SARS and MERS.

The general approach that Novavax uses to make its vaccines consists of producing the proteins, which aggregate to produce virus-like particles, or VLPs that, to the immune system, and look a lot like a viral shell. The company is using the VLP approach to develop vaccines for respiratory syncytial virus and seasonal and pandemic flu strains.

The company has findings from both the NIH and the Biochemical Advanced Research and Development Authority for its pandemic vaccine programs, and so working on a MERS vaccine requires a "minimal investment," on the part of the company, Smith said. "And we learn things for our other programs."