MARIAGNY TASET and ORFILIO PELÁEZ

On the first day of July, 1986, the Center of Genetic Engineering and Biotechnology opened up its doors to the world. Cuban science achieved a giant and complex leap that has boosted the development of these research areas for the benefit of all mankind.

Such an audacious decision required at that time, not only the skills of highly qualified specialists, but also the availability of a solid and up to date technological infrastructure, an almost exclusive privilege of the so called First World.

For a nation under the siege by a blockade and with limited resources it was an unbelievable event. In those times, when the Center was inaugurated, Fidel was optimistically saying: the building and the installations are large, but my aspirations are that the results achieved will also be large. And his words were of such a prophetic nature that today, twenty years later, the results are an unquestionable reality.

Suffice to mention the anti hepatitis B recombinant vaccine (Heberbiovac HB ) a flagship product of the Center of Genetic Engineering and Biotechnology ( CGEB ), that is registered in more than 32 nations of Latin America, Asia, Africa and Europe. It is a vaccine that, when introduced for use in the Cuban National Health Care System, has achieved the eradication of the acute infantile hepatitis B. At this moment all the Cuban population under age 25 has been immunized against this disease with the Heberbiovac HB vaccine.

Another outstanding product is the recombinant vaccine under the name Gavac, which combats ticks in cattle. Its use has made possible a substantial reduction in the incidence of ticks and the mortality rate caused by blood transmitted diseases that are propagated by means of ticks.

The use of Gavac was extended to the whole nation in 1999, making savings in the order of more than 10 million dollars every year possible, because anti-tick chemical products imports, traditionally used to combat ticks, could be reduced by almost 90 percent.

As explained recently by Doctor Luis Herrera the Director General of CGEB, the institution has recently developed novel products, like Citoprot-P for the treatment of foot ulcers of diabetic patients, and the first recombinant monoclonal antibody obtained from genetically modified plants, ( plantibodies ), that is destined for the production of the hepatitis B vaccine in order to make it more competitive.

The art of knowing how to carry out scientific and technological research and to put it into production with excellence has been the key to the achievements of this scientific institution.

This is also demonstrated by the so called combined vaccines, one of which known as

Trivac-HB, that is capable of providing immunization against four diseases with a single product and is an excellent example of the center's achievements.

A VACCINE WITHOUT PRECEDENT IN LATIN AMERICA

Maria is proud of being Cuban. She has not got enough fingers to count the reasons, but among the first ones she says this one: "Because in Cuba everything is for the people. Just imagine how much I would have to pay in another country to have my girl immunized with this vaccine ! "

She said it one morning right in front of the vaccination office of her local clinic, where she was waiting for her two months old baby girl Melissa to get the first doses of the Trivac-HB vaccine that will immunize her against four communicable diseases, " so that she will not be affected by Whooping cough, tetanus, diphtheria and hepatitis B, and I won't have to come back here again for two months, because with this new vaccine, the number of injections required is less and so I have to make less trips to the clinic".

The world has seen the introduction on a commercial scale of several vaccines, of new or improved types, that are effective in the prevention of different diseases. But on occasions, the introduction of these medical products increases the costs involved in the national immunization programs (vaccines represent about 20 percent of the investments involved)

As a solution, Doctor Eduardo Martinez Diaz, a researcher at the Center explains that new combined vaccines began to be developed. That means that the new combined vaccines provide protection against several diseases in one single product. By using these new multiple purpose vaccines the risks of injection related problems diminish, and the same holds for refrigeration, storage, transportation and handling needs, as well as the new benefits that they provide for the patient.

Cuba has the advantage of producing several antigens ideal for generating multiple purpose vaccines, which are aimed for use at home as well as in other countries.

Among those vaccines Trivac-B is a good example. It was under research since the nineteen nineties by experts of different Cuban scientific institutions, and it received two National Academy of Sciences Awards in 2005.

This is the first vaccine of its type in Latin America, which competes at a worldwide level, assured Nestor Exposito Raya M.Sc., one of the main researchers behind this product, with an added value which makes it a very attractive product to be commercialized.

The way that this vaccine is presented for delivery is preferred by the majority of the nations, but the high prices of combined pharmaceuticals- monopolized by a few transnational corporations- and their lack of availability, hinder access to them. Before the Cuban Trivac-HB tetravalent vaccine was made available, there was only one equivalent product with similar characteristics, sold under the trade mark Trintanrix-HB, by the Belgian firm Glaxo-Smith-Kline.

The patent that protected that vaccine gave very little leeway under which to work. We researched a variation that had been tried unsuccessfully at an international level, and the high purity, aggregation and stability of our HB antigen, together with the effectiveness of the Cuban proprietary technological process, allowed us to develop to the level of the existing vaccine.

From a scientific point of view, the Cuban researcher underscored, the greatest achievement was the strategy of the formulation. Trivac-HB is not a simple mixture of ingredients. You also have to take into consideration the immunological interference and chemical compatibility between its components. This type of vaccine must be stable for at least a period of two years. Ours was stable, in fact, for a 30 months period.

For its manufacturing the Center provides the HB antigen against Hepatitis B, and the Finlay Institute provides the rest of them (diphtheria, whooping cough and tetanus antigens) . They are all produced under strict high standards of Good Practices.

This guarantees a unique technology and makes it possible to develop a tetanus toxoid of high purity, which can be used successfully in all the liquid formulas that require it, according to a statement by Doctor Daniel Cardoso Gonzalez Ph.D., another of the main contributors to this project at the Finlay Institute.

Since 2004, the Trivac-HB vaccine has been produced on an industrial scale at the Center of Biopreparations ( BIOCEN ). In the early stages their batches reached barely 20 liters, something that required the use of many laboratory resources, required during the 19 physical-chemical and biological trials that are needed to be able to deliver the product for use.

In the year 2005 we decided to start producing 100 liter batches, explained Doctor Orestes Mayo Abad, a specialist at the Development Department of BIOCEN. By changing to these larger sized batches, the number resources required for the trials could be reduced, so productivity was increased fivefold.

This was the most significant experience of large scale formulation at the center, according to Joel Perez Gutierrez MSc, the Head of the Engineering Quality Control Department. Trivac-HB has the most complex formula with which we work. To making it we had to adapt a reaction vessel with the required capacity for the larger batches, from another system at the Parenteral Products plant, where this pharmaceutical product is now produced.

At this moment, the Cuban tetravalent vaccine is distributed at a national level, and is in the registration phase in Asia, Africa and Latin America. It has served as the basis to develop other vaccines, like the pentavalent one, which also immunizes against Haemophilus influenzae type B, a bacterium that can cause meningitis and pneumonia in children under five years old.

Two decades of efforts and creativity validate the strategic decision to create the Center of Genetic Engineering and Biotechnology. To the amazement of many, today its products are saving lives, wiping away diseases, improving animal husbandry, which increases the availability of food supplies and, if this was not enough, they are competitive in the tight race with the best similar products in the world.

Source: Granma