Vaccines and Sovereignty (III)
The Antigen of Cuban Vaccines Against Covid-19

By Luis A Montero Cabrera
January 21, 2021

Translated by Merriam Ansara for CubaNews and other outlets.

This is the third in a series of articles.

The application of the Cuban Sovereign vaccine candidate begins. Photo: Ismael Francisco/ Cubadebate.

We Cubans have a very remarkable platform for biomedical production, one might even say extraordinary for a country like ours. An infamous 2004 document from the “Commission for the Support of a Free Cuba” of a previous administration in the US described it as unnecessary and very expensive for such a poor country as ours:  “Large sums were also directed to activities such as the development of biotechnology and bioscience centers not appropriate in magnitude and expense for such a fundamentally poor nation, and which have failed to be justified financially”.  The only thing to be added to this is that those of us in the South with darker skin ought not to have the luxury of science.  But our biopharmaceutical sector is the child of necessity, of the creative initiative of a lover of knowledge and a true revolutionary, as was our Fidel, and of an educational policy that gives everybody without distinction the right to reach the highest level of human knowledge and to with that knowledge, create.  It was not begun with a specific strategy or goal but became, as it is today a bastion of the knowledge, science and culture of our country.  It was and is the fruit of revolutionary thinking.

The development of a vaccine today requires the existence of today’s conditions for this kind of research.  It must begin by looking at the scientific literature for antecedents and ways of doing things that can lead to the implementation of more and more exquisite laboratory procedures and rigorous tests. In our case and for the above reasons, a firm base for the research was already established when the COVID 19 emergency arose. Events such as these cannot be foreseen, but the preparation of the conditions to face them is the duty of any decent political system.

Chinese science immediately made available to the international community everything it knew about this dangerous and ultra-contagious virus and in other countries as well the information that was being generated was made available to all. Under these conditions, several of our scientific groups set to work to obtain a specific Cuban vaccine for this disease. One of the efforts, at the Finlay Vaccine Institute, is led by the same Prof. Vicente Vérez who obtained the previous milestone of the vaccine against “Haemophilus influenzae”, the first with synthetic antigens that was used and commercialized in the world. The other groups involved work at the Center for Genetic Engineering and Biotechnology with a long tradition also in the design and production of novel vaccines.

Remember that the essential component of a vaccine is the antigen that activates the immune system and leaves it ready to fight and destroy the foreign invader. Additional determining factors are both the adjuvants and the pharmaceutical forms for delivering the vaccine to humans. If you have an established and strong foundation in these last two aspects, determining the most suitable antigen becomes the heart of the creative work.

The antigen chosen in Cuba, for many reasons, was the “receptor-binding domain” of the virus (RBD). In simple terms, these are the molecules that constitute the external “spikes” so striking that they appear in the pictorial representation and the high-resolution microscopy of the viral molecular aggregate. This CoV “spike” protein (S) plays the most important role in viral binding, fusion and entry into cells of the organism attacked by the virus.

Therefore, it serves as a target for the immune system to develop antibodies, and for scientists to use them as antigens in the design of effective vaccines. An article that appeared in one of the branches of the well-known journal Nature had characterized this component as very promising as a vaccine antigen against COVID 19 as early as March 2020. The authors of the article are a very good reflection of the current internationalization of the basic sciences.  Most are Chinese in origin and did extensive work in collaboration between the Lindsley F. Kimball Research Institute in New York, the Beijing Institute of Microbiology and Epidemiology, and the Key Laboratory for Medical Molecular Virology at Fudan University in Shanghai.  

Our compañeros evaluated alternatives. One of them was to generate the so-called messenger RNA that was capable of producing the antigen in human cells. It is an ultra-modern technology that is being used in some of the COVID 19 vaccines that are already being applied. It has some advantages, but also has an important disadvantage so far not overcome for a vaccine that is intended to be administered massively throughout the world, especially the less developed one: it requires very strict cooling conditions for its transport and preservation.

Our biotechnology system, on the other hand, has at the Center for Molecular Immunology (CIM) the possibility to “ferment” mammalian cells that directly produce the RBD antigen, since the technology has been developed for other similar productions. It also has the possibility of producing a significant quantity if the antigen is viable for our vaccine. Therefore, all Cuban vaccine candidates, at least up to now, are based on this antigen, with some modification that makes it more active.

The results are exhilarating. And thus our scientists began the race to produce a variety of vaccines, in different institutions and by different scientific groups, collaborating and competing, in order to arrive at the best solutions. “SOBERANAS” 1 and 2, the MAMBISA and the ABDALA are very promising.

Vaccines are drugs. Therefore, they require measurements of their effectiveness, knowing their contraindications and risks, and finding the appropriate formulations and the most viable forms of administration before applying them en masse. Everything must proceed in a strict regulatory framework to ensure that consequences more serious than the disease itself were avoided. If they have the same antigen, how are our vaccine variants different? What state are they in their research and development?

Havana, January 20, 2021

Luis Alberto Cabrera Montero holds a Doctorate Chemical Sciences.   He is Senior Researcher and Full Professor at the University of Havana. He is President of the Scientific Advisory Council of the University of Havana and is a Merit Member and Coordinator of Natural and Exact Sciences of the Academy of Sciences of Cuba.  For a full biography, see http://www.academiaciencias.cu/en/node/674

Vaccines and Sovereignty (II):
What are Vaccines?

By Luis A Montero Cabrera
January 11, 2021

Translated by Merriam Ansara for CubaNews and other outlets.

This is the second in a series of articles.  

Seventy coronavirus vaccines are in development worldwide, and three are already being tested in human trials, the World Health Organization said. Photo: iStock

The molecules of an invading biological entity that are identified and are accessible to the human immune system are often referred to as “antigens”. They are usually expressed in the outermost parts of the nanoscopic carrier and are a necessary part of its composition. They are the same when found in a virus, in a fungus, in a bacterium, or in the cells of an organ from another being transplanted into our body.

An important characteristic of the infection and self-healing process is that when an individual overcomes a disease by the action of the immune system, it usually remains prepared to defeat it in future reinfections of the same type. The system “remembers” the intruder antigen and thus we are prepared to reject its carriers again. It is a biological fabric very refined by natural selection through many generations and species.

By realizing this, and using scientific reasoning, human beings try to use this defense “memory” to ensure that people do not get sick with an infection, even if they have never suffered from the disease. It is about “teaching” the immune system of each individual to activate and destroy any morbid invasion once its antigens are detected. The challenge is great, because to invade the body with antigens from a certain infection without making the person sick requires wise processing.

The result is known as a “vaccine.” Its name is due to the fact that the first formulations were cultivated in cows. It is always a chemical-biological preparation of antigens to achieve active acquired immunity against a particular infectious disease. The first vaccines contained the organisms that caused the disease from weakened or dead forms of themselves. It was not known then that what the immune system recognized was only its antigens. These preparations thus “taught” the human body to “shoot” the actions that would destroy the invader. Vaccines can be prophylactic when they prevent and prevent the effects of future infection, as it is desired that COVID-19 be, or therapeutic when they are used to fight a disease that has already invaded the body, such as cancer.

Most likely, the first disease to be prevented by inoculation was smallpox. It seems that the first recorded use of it occurred in the 16th century in China. The scientific and reproducible vaccine against smallpox was invented and duly reported in the specialized literature in 1796 by the English physician Edward Jenner. Smallpox was a contagious and deadly disease, and it is said to kill up to 60% of infected adults and 80% of children.

Tomas Romay y Chacón was a physician and scientist born in Havana in 1764. Having begun by studying law he switched to medicine and in 1791 at the age of 27 was 33rd medical graduate in Cuba. He became a professor at our University of Havana and co-founder of the Royal Patriotic Society of Havana, today the Economic Society of Friends of the Country. As early as 1804, just 8 years after the appearance of the vaccine in Europe, Romay implemented smallpox vaccination on our island with preparations made “in situ” with the support of the Patriotic Society. In this way, he used the local science instead of waiting for delayed arrival of the vaccine from the Metropolis. He and his collaborators followed the procedures published and described by Jenner and manufactured the first Cuban vaccine, the smallpox vaccine. A marvelous success of a nascent, Creole, nation’s innovation and wisdom.

Time passed and scientific research led to the knowledge that the key to vaccines were the antigens and not the entire infectious entities. 

Vaccines have been produced in Cuba for many decades. Two of them at least have been both original and exclusive. In 1987 Drs. Concepción Campa and Gustavo Sierra led a scientific group at the Finlay Vaccine Institute to obtain a vaccine that at that time was the first of its kind in the world. This vaccine was and still is very effective against a bacterium that attacks the meninges in the brain and nervous system, called group B and C meningococcus. This type of meningitis is particularly deadly in children. Cuban science at the University of Havana produced in 2004 the world’s first efficient commercial vaccine based on an antigen manufactured in the laboratory, that is, “synthetic”.  Prof. Vicente Vérez, a scientist who has dedicated his life to the chemistry of sugars, his wife Dr. Violeta Fernández (who died very young) and their collaborators were the authors of this second great feat. Thanks to the work of these scientific groups, many Cuban children and children in many parts of the world are alive and active today as adults.

Vaccines don’t just contain antigens. The immune system is not equally effective in all people and at all ages. Certain antigens are more activating than others because they are more easily recognized and “trigger” the work of the entire system that feels invaded. Vaccines are made more effective with so-called “adjuvants” (helpers) which, when given together with the appropriate antigens, cause many people’s immune systems to wake up more quickly and efficiently.

New types of vaccines have recently appeared that do not contain antigens directly but rather RNA that allows our cells to synthesize them “in situ”, recognize them and learn to fight them. While the vaccines that contain only antigens without the need to supply the infectious agent are efficient and safe, these others are as well and furthermore allow for mutations of the virus to be taken into account with much greater facility and so ensure the utility of the vaccines over time.

It can be said that vaccines are pieces of biological technology that represent a lifeline for many human beings. Without them we would be at the mercy of Darwinian natural selection and an epidemic would be survived only by the few who could overcome it thanks to some singularity of their organism. This was the case before science intervened by inventing vaccines. The cost was immense in precious lives ending early. It could also be said that without vaccines some type of infection could come along that might lead to the extinction of homo sapiens as a living species, which has happened many times before with other species in the beautiful and harsh history of life on this planet.

And what will the current vaccines against COVID and very particularly the SOBERANAS, MAMBISA and ABDALA be like? How do you prove that they serve what they have been designed for?

Havana, January 6, 2021

Luis Alberto Cabrera Montero holds a Doctorate Chemical Sciences. He is a Senior Researcher and Full Professor at the University of Havana. He is President of the Scientific Advisory Council of the University of Havana and is a Merit Member and Coordinator of Natural and Exact Sciences of the Academy of Sciences of Cuba.  For a full biography, see http://www.academiaciencias.cu/en/node/674

Vaccines and Sovereignty (I):
The virus and the immune system 

By Luis A Montero Cabrera
December 31, 2020

Translated by Merriam Ansara for CubaNews and other outlets.

This is the first in a series of articles.  

A vial of COVID-19 vaccine from Pfizer and BioNTech, Boston, Massachusetts, USA, on December 16, 2020. Illustrative image: Craig F. Walker/Pool / Reuters

The word we all speak today with hope is “vaccine.” We have had an absolutely extraordinary 2020’s year. An unexpected and unprecedented pandemic has changed everything, in almost every way for the worse, although there also have been some good consequences. The political defeat of some enemies of our country who did not even know how to lead their powerful country in these extraordinary conditions may have been influenced by this factor, and that is a good consequence. That and the vaccines, four of them Cuban, mean a more optimistic outlook for 2021 for us. Unfortunately, those who lalready lost or will lose their lives to this pandemic will not be able to take advantage of what little good there is in the remains of this pandemic.

We already know how life originates, how it works and how it manipulates the laws of the rest of the universe to perpetuate itself, more as a system than in its individualities. Within that system of life, viruses appear at a given moment and have their own space. The one that has caused the current pandemic is only one of the many that exist and that have existed, and it will by no means be the last that affects humanity and other living beings. They can arise anywhere and will or will not spread depending on their characteristics and how science influences where they occur.

Molecules are inanimate particles of the nanoworld since their sizes are around one billionth of a meter. Some of them act as the “bricks” and “cement” that make up living organisms. There are many types of molecules that are part of this network and the most unique and complex are proteins (which are the ones that “work” and are also part of the functional structures), fats (which “cement” and store energy), sugars (which cement and hold, but in a much more specialized way, and also accumulate and transport energy), and the so-called “nucleic acids”. The latter are very special and complex molecules whose fundamental function is to accumulate the information of the living system so that all the others can exist.

Viruses are not living beings, but relatively stable aggregates or associations of various types of vital molecules, the fundamental component of which are nucleic acids. In this case, they carry their own information, but foreign to the system of other living organisms. However, they include the ability to self-replicate at the expense of the animal or plant, including us, in which they are housed. They change (or mutate) in the environment in which they develop and out of the many ways in which this happens, the vast majority fail. However, the few mutations that turn out to be successful put the cells they invade at their service to give rise to new viruses. And in that task, it always affects in one way or another the host cell that lent it its resources. If the virus is COVID-19, it seems to affect the cell to such an extent and in such a way that even the ways we defend ourselves against them can kill us.

There is a great debate among virologists about the origin of viruses. Three main hypotheses are usually mentioned: i) The “progressive” hypothesis that states that viruses arose from genes (made up of nucleic acids) in cells that showed the ability to move or transfer to other cells; ii) the “regressive” hypothesis proposes that viruses are genetic remains of dead cell organisms that showed the ability to be assimilated by other living cells and to reproduce there; and iii) the “primary virus” hypothesis proposes that viruses precede cells in evolution: they would have appeared first. For this reason, they may have been the initiating molecular aggregates of the ability to self-reproduce. If this is the correct hypothesis, it would make them predecessors of cells and in conditions of “coevolution” with them, which are their current hosts.

A living system such as the human being that has evolved in the last 3.7 billion years has very efficient ways to defend itself against potentially harmful agents that are carriers of foreign molecules. We do this through what is known as the “immune system.” This has a complex form of action, which can be understood in a simplified way.

The immune system of our body recognizes the vital molecular structures that are our own and not those of others. Our natural “identity card” is in the genes. Once our mother’s egg was fertilized by our father’s sperm, our genes became differentiated from theirs. We constitute ourselves as a new living entity similar to but different from that of our parents. Only a certain part of our cells preserve the identity of our mother.

Among all the information that is transmitted is also that of the system that identifies its own vital molecules with respect to those of any other living entity. These characteristic molecules of bacteria, fungi, viruses and all possible living beings can be of very different types. They are called “antigens.” The wonderful human immune system is capable of identifying foreign antigens that penetrate our body and generating an arsenal of its own components that are responsible for destroying their carriers.

If the invasion is by bacteria, or any other living alien organism, then they identify their foreign antigens, design the appropriate molecules to associate with them, and from there the life span of the invading organism is counted. The intruder can win only if our immune reaction is less efficient than the intruder’s harmful action or if the action of the intruder damages the immune system specifically. Viruses and the cells they infect are identified and killed in a similar way.  AIDS, for example, originates from a virus that affects the immune system, and thus it is very difficult to overcome.

How, then, can a disease caused by a virus-like COVID-19 be defeated?
Essentially in two ways: the first is to combat and neutralize the effects of the virus on the diseased organism, which has been attacked. It is achieved with effective treatments. The second is to help identify and destroy the invading species by our own immune weapons. This can be achieved by “teaching” the immune system to do its job, but without the symptoms of the disease that can be fatal. That is “to get vaccinated” against the virus.

Luis Alberto Cabrera Montero holds a Doctorate Chemical Sciences. He is a Senior Researcher and Full Professor at the University of Havana. He is President of the Scientific Advisory Council of the University of Havana and is a Merit Member and Coordinator of Natural and Exact Sciences of the Academy of Sciences of Cuba.  For a full biography, see http://www.academiaciencias.cu/en/node/674