Dyadic International Inc (DYAI)

[dennisczy]

googie from microcapclub said this about trump's exec order on the flu vaccine. I think it's really good and detailed, so I've copied and pasted it here. I also read from nature that "A highly effective seasonal flu vaccine, produced rapidly at the start of an influenza pandemic, would save the United States an estimated US$953 billion by preventing deaths and hospitalizations, according to the White House Council of Economic Advisers."

https://www.nature.com/articles/d41586-019-02831-x



Googie:
given the cost savings that could be achieved, there's no reason that they would settle for a less efficient method I think

"Dyadic views President Trump's executive order to improve flu vaccines as a major opportunity." I knew almost nothing about flu shots, but Dyadic was calling it a "major opportunity" so I googled around a bit. Here's some thoughts for anybody that's interested.

A decision is made in February every year as to what strains should be included in the next fall's flu shot. The decision is made so early because it takes a long time to produce enough flu virus. Incubation in eggs is the primary means, although a second method allowing the virus to reproduce inside cells can also be used. Flu shot makers sometimes start growing virus in eggs in January if they have some confidence some virus strain will be included in the February decision. It takes 6 months or so to produce enough virus. Some virus variants don't grow well in eggs and others mutate while reproducing in the eggs. These two problems sometimes limits production of the needed virus strain resulting in a less effective flu shot.

Another source of ineffectiveness is that between the February decision and the fall flu season, the virus mutates in the population. Some new strain arises that the flu shot doesn't protect against. This can result in a pandemic, and the flu can be deadly as it was in 1919. If such a pandemic arose, it would take 6 months to create a new flu vaccine that would protect against it.

"There is a third production technology for flu vaccines that was approved for use in the U.S. market in 2013 and that involves using recombinant technology. This production method does not require an egg-grown vaccine virus and does not use chicken eggs at all in the production process. Instead, manufacturers isolate a certain gene (the hemagglutinin or “HA” gene) from a naturally occurring (“wild type”) recommended vaccine virus. This HA gene is then combined with portions of another virus that grows well in insect cells. This “recombinant” vaccine virus is then mixed with insect cells and allowed to replicate in these cells. The flu HA protein is then harvested from these cells and purified. The purified protein is packaged while waiting for FDA testing and approval to release lots. Currently, recombinant flu vaccine is the only 100% egg-free vaccine on the U.S. market.

The recombinant flu vaccine marketed by Sanofi as "Flublock Quadrivalent" is produced using the baculovirus (an insect cell) platform that they purchased (for $600+ million) from Protein Sciences. An advantage of recombinant technology is that the HA gene of the flu variant can be transferred to the baculovirus which can then produce flu vaccine relatively quickly. One could perhaps delay the decision on which flu strains to include until the summer instead of February. Recombinant vaccines should not suffer from the problems with getting some strains to grow in eggs or with the virus mutating so much as to become significantly different from the virus prevalent in the human population. Most importantly, in a pandemic, it should be possible to create an effective flu vaccine perhaps in a few weeks (my guess) instead of 6 months.

Sanofi evaluated using C1 instead of the baculovirus in 2015. Dyadic's slides (http://www.dyadic.com/wp-content/uploads/2018/01/Sanofi-Pasteur-C1-Presentation.pdf) show the C1 version to create superior immune response in mice than the baculovirus version even at a lower dose. C1 is also highly productive with the company projecting they can create the global demand of 146 million doses with just three 1000 liter fermentations. There was no weight loss or other adverse reactions observed in the mice. Getting FDA approval obviously would require human testing and who knows what else.

But slide 32 of this presentation https://www.dyadic.com/wp-content/uploads/2019/01/NOBLECON15-January-2019.pdf) hints at possibly the most important reason one might use C1 instead of baculovirus, "the potential to speed the development time". This comment probably reflects that C1 ferments in just 3 to 7 days, important in a pandemic. That quick incubation time may be more important than you'd think if several tries are required before the genetic modifications are verified to produce the right stuff. Maybe there's other reasons it could be quicker such as the genetic engineering can be done faster than for baculovirus. Dyadic doesn't elaborate on "the potential to speed development time" comment.

Sanofi has the only quick to produce recombinant flu vaccine that is approved in the USA. I'd think they would be all over Trump's executive order to modernize the flu vaccine. Recombinant seems the way to go because of quicker production times allowing more effective vaccines and effective responses to Pandemics. Whether Sanofi would want to propose C1 instead of their owned baculovirus is a fine question. If Sanofi doesn't propose C1, perhaps a competitor's proposal would.