The biotech vaccine that wants to save the world

March 15, 2017
Pandemic outbreaks of influenza, like the one in 2009 in Mexico, can cost thousands of lives and cost billions. Traditional vaccines take up to six months to reach the market, but the vaccine has the capacity to be produced in less than four weeks … and is now available in Mexico.

New York, NY. Experience is not, as close as you can imagine it. When you arrive at the plant that manufactures the first biotech influenza vaccine, ready to tour your facility, you naturally expect to be offered an airtight suit, like any scientist would use in a biological threat film. But, no: although Protein Sciences facilities in upstate New York produce about five million shots each year, when you enter, you are only asked to wear a surgical gown, covers and a hairnet; The goal is not to prevent your contagion, but to prevent you from contaminating the facilities.

“While other laboratories need a live swine flu sample to make their vaccines, we just need an email from the World Health Organization (WHO) with the DNA sequence of the influenza strain, so We do not manipulate live viruses, “says Dan Adams, chief executive officer and director of Global Business Development at Protein Sciences, the company that developed Flublok, the first recombinant (genetically engineered) vaccine against influenza virus.

There is nothing simple in the process of making a vaccine. Traditionally, pharmaceutical laboratories use eggs, millions of them, as a culture medium for a version of a living microbe that has been inactivated and fragmented in the laboratory so that it can not trigger the disease once it is injected into the human body. It is a method in which the vaccine presents egg residues, as well as a considerable amount of by-products (including latex and antibiotics), which can generate adverse reactions in patients sensitive or allergic to these substances.

But beyond that, perhaps the biggest disadvantage of this method of manufacturing is the slow process, which can take up to six months, an eternity if a pandemic is reported.

In the case of a recombinant vaccine, such as that made by Protein Sciences, the process is different and purer. Its technology allows to know the genetic sequence of the DNA that generates the hamaglutinina, that is to say, the protein responsible for the protection against the disease. This protein is produced in a cell culture line patented with the name ExpressSF +, under the three types of influenza indicated by the WHO and that, for this season, were H1N1, H3N2 and B.

The use of recombinant vaccines is not new, but no effective use of influenza has been confirmed. Recombinant vector vaccines simulate a natural infection and, therefore, are effective in stimulating the immune system. Successful use of this technique “represents a breakthrough,” wrote Dr. Jerry P. Weir, director of the Viral Products division at the FDA’s Biological Evaluation and Research Center (FDA) English), an agency that evaluates and approves new drugs that seek to reach the market.

“This is a revolutionary breakthrough that will replace the current egg vaccines. The more manufacturing alternatives we have, the better we can respond to public emergencies in a timely manner, “added Weir.

So far, Flublok has received the FDA approval in the United States and Cofepris in Mexico, to be administered in adults over 18 years, but Protein Sciences and Liomont and already prepare their study in children.

 

In case of a pandemic

The images went down in history: It was the last days of May 2009 and the streets of the then Federal District, the capital of Mexico, looked deserted at noon. A health alert had forced local authorities to issue a state of alert and to impose the closure of public facilities, such as cinemas and theaters, and to limit restaurant service to just preparing takeaways.

According to figures from the Ministry of Health, this health crisis cost Mexico at least $ 4 billion, or 0.4% of the Gross Domestic Product (GDP), despite the fact that the number of confirmed cases during the year was Of 54,000; Of them, only 398 died. That is a lethality rate of 0.73%, far from 50% of the Ebola virus.

In a public letter, Margaret Chan, then director of WHO, justified giving the contingency the degree of pandemic: “The analysis of laboratory samples showed that the new virus had never circulated before in the human species. It is a virus of animal origin that uniquely combines genes of swine, avian and human influenza viruses. The genetic makeup of this virus is very different from that of H1N1 viruses that have been causing seasonal epidemics since 1977, “Chan said.

“WHO’s main fear is that it will spread from animal to human and that it will develop the ability to infect other humans. It would be highly deadly because humans have no defenses against it, “explains Dr. Alicia Galván, medical director of Laboratorios Liomont, the Mexican company that licensed Flublok’s distribution and manufacturing rights to Latin America except Brazil and Argentina.

“This vaccine is revolutionary because it can take us only four weeks to have it ready for the public, unlike the traditional one, which took up to six months. This, in a pandemic case, is something shocking: we have the reaction time to be able to protect the population, “adds Galván.

That time of reaction would have saved billions of dollars in the scenario of the crisis generated by the H1N1 virus in Mexico in 2009; But to understand it, you first have to understand the dynamics behind the influenza virus.

To tame them all?

The first thing to know is that there is no single influenza virus and that strains are constantly changing. That is why there is no vaccine that, with a single dose, immunize for life, so the WHO has to constantly monitor the cases recorded around the world to define what the three predominant strains in the year.

Once WHO has decided which strains will be the most common, it advises pharmaceutical laboratories around the world to prepare seasonal vaccines for the season, a process that usually lasts six months.

All this process would be extremely effective, except for the fact that Mother Nature is capricious and unpredictable and that, from time to time, she likes to play tricks on men, as in 2005, with the bird flu virus ( H5N1), or in 2009 with swine flu (H1N1), whose strains went unnoticed by WHO and showed a risk of contagion of alarming proportions, forcing the agency to declare the disease as a pandemic. Both outbreaks highlighted the need for alternatives to the production of so-called pandemic vaccines (which only include one strain, in these cases H5N1 or H1N1), which could prevent new infections quickly and effectively, serving as a sanitary fence . But, no: the first vaccines were ready much later.

 

 

 

Made in Mexico

In our country, where currently 54 million Mexicans over the age of 18 are not vaccinated against influenza, there is a business opportunity of as great a size as the challenge of convincing them to do so. “The whole population has to be vaccinated. It does not matter if you already had influenza at any time in your life, again you have to do it because, every year, the virus has a different strain, “warns Dr. Galván.

Against this background, Laboratorios Liomont, a Mexican company dedicated to the manufacture of generic drugs, decided to create the Life Sciences division in 2014, and start developing biotechnological products, explains the doctor.

The approach between Liomont and Protein Sciences was for several years, when Sergio Valentinotti, director of the Life Sciences area in Liomont, met Flublok and tried to bring it to Mexico, but it was not until 2014 when both companies signed a licensing agreement Distribution in Latin America, except Brazil and Argentina.

 

“In November 2015, regulatory processes for the registration of Flublok in Mexico began, and this year it is already available in the market,” explains Oscar Gamiz, Director of Marketing for the Division of Life Sciences in Liomont.

 

“Ideally, the entire population should be vaccinated, but we know that it is complicated. What we are looking for with this product is to increase the coverage. Currently, the private market is around 300,000 doses and the public, which are the doses applied by the government, total 34 million doses. That is a really important effort of the health authorities. The public market is key and, of course, our goal is to cover it with local manufacture, “explains Gamiz.

 

To do this, Liomont builds a manufacturing plant in Ocoyoacac, State of Mexico, which will have the same capacity as the Protein Sciences plant in New York: 5 million trivalent vaccines (with three strains issued by WHO) per year, or 15 Millions of pandemic vaccines (with a single strain). “The plan is to supply the government with this plant for the 2020 season,” when the plant will be finished and in operation.

In 2016, Liomont brought Mexico the first 50,000 doses, all of them dedicated to the private sector, and expects to double them by 2017. “For now, that figure does not represent an interesting profitability for the laboratory, but our expectation is to receive the finished Protein Sciences and conditioning it in Mexico, lower costs, maintain the same preferential price and increase volume, “says Dr. Galván.

 

According to the directive, “the biggest cost of a product is not manufacturing, which can be very simple, but investment in clinical research.” Dan Adams, CEO and Director of Global Business Development at Protein Sciences, agrees: “This, in particular [Flublok], took us 20 years. It is difficult to determine how much it cost us, because we have received a lot of support from the authorities [the US government paid $ 147 million for an assured lot of the vaccine] and the US Department of Health and Human Services supported us with clinical trials . In total, developing Flublok probably cost us about 300 million. ”

 

Currently, Protein Sciences works on a tetravalent version of Flublok, as well as on recombinant vaccines to combat rabies and zika virus.

 

Liomont wants to replicate that success and is therefore dedicating resources to acquiring more licenses for biotech drugs, as well as research (it does not say the amount). In fact, it already works with the Biotechnology Institute of UNAM to “develop several innovative products that we are visualizing to manufacture, design and study in Mexico, with a view to being exported to Europe and the United States,” adds Dr. Galván.

 

Until now, Mexico is one of two countries that have made real efforts of production of Flublok; The other is Japan, who bought the technology and builds a plant that will be able to manufacture up to 30 million doses of seasonal influenza vaccine and 90 million pandemic vaccine.

 

Protein Sciences hopes Flublok will soon be produced in Brazil, Argentina and Qatar, but also works on new vaccines for rabies, zika and Ebola under the same biotechnology approach. These products are likely to take some time to reach the market; But with Flublok, the company is not only able to protect the population safely and effectively, it is also ready to deal with a pandemic, and has turned around an old question: what went first: the egg or the vaccine?