According to the World Health Organization (WHO) \u201ca vaccine is understood to be any preparation intended to generate immunity against a disease by stimulating the production of antibodies. This may be, for example, a suspension of killed or attenuated microorganisms, or products or derivatives of microorganisms. Most vaccines are given by an injection, but some are given orally (by mouth) or sprayed into the nose.\u201d<\/em><\/p>\n What does it mean to generate immunity by stimulating the production of antibodies?<\/strong><\/p>\n The immune system is like the body\u2019s defense army, and it is a complex army where different body organs and cells participate. From the moment we are born we have the ability to defend ourselves against external agents that can pose a threat to health, when these are biological entities capable of causing diseases they are called pathogens<\/strong>. There are many pathogenic microorganisms for humans (bacteria, fungi, viruses, parasites). When we come into contact with them, our body has certain defense systems prepared, and this pathogen has to overcome physical and biological barriers to enter our body, multiply and cause disease, this first line of defense is called innate immunity<\/strong>.<\/p>\n However, the proof that this innate immunity is not enough is that we get sick, that we catch colds, or get diarrhea of \u200b\u200bviral or bacterial origin, or chickenpox, or tuberculosis, or hepatitis, or lesions on the skin caused by fungi, or HIV, or herpes, among many other infectious diseases. That\u2019s because that rapid first response is not specific to each type of pathogen and is not always powerful enough to protect us. So our body has designed another line of defense: acquired immunity<\/strong>. Many times we hear our grandparents say: let the girl walk barefoot, she has to get antibodies\u2014almost always the accumulated wisdom has some reason. I would like to say that acquired immunity, which is a slower, but more specific and efficient response, is not only about antibodies, but these play a very important role in protecting against infectious pathogens.<\/p>\n What are antibodies?<\/strong><\/p>\n One of the most powerful weapons of the immune system is antibodies (also known as immunoglobulins). Antibodies are molecules (glycoproteins) produced by a type of cells of the immune system (T lymphocytes). When our body comes into contact with a pathogen, T lymphocytes are activated and produce antibodies against that specific type of pathogen.<\/p>\n Antibodies have two main functions: they mark these pathogens to be attacked and killed by other cells of the immune system, or they are bound by a specific part of the pathogen that blocks their ability to enter and harm cells in the body.<\/p>\n Antibodies (which are such specific molecules) are not generated against the entire pathogen, but against parts of them, that substance (that part of the pathogen) that generates the production of antibodies is called antigen<\/strong>.<\/p>\n Pathogenic microorganisms are complex structures. Determining within them which antigen is going to generate an immune response powerful enough to protect us from disease is one of the most important steps in the design of a vaccine of this type.<\/p>\n The objective of a vaccine is to put us in contact with the pathogen (or with its specific antigens) in a safe way\u2015without causing the disease\u2015so that our immune system produces these specific antibodies, because once produced our immune system will keep that \u201cmemory\u201d and if we come into contact with the live or active pathogen, all these \u201cspecific weapons\u201d will be ready, the response will be faster, most of the time it will protect us, and if we contract the disease it is usually much less serious.<\/p>\n COVID-19<\/strong><\/p>\n The current pandemic is caused by a virus. Within microorganisms, viruses are very particular entities. While bacteria and fungi can live and reproduce in various environments: land, air, water, rocks, minerals…viruses are obligated intracellular parasites, that is, they cannot reproduce outside a cell.<\/p>\n A virus<\/a> is a small collection of genetic code, either DNA or RNA, surrounded by a protein coat. A virus cannot replicate alone. Viruses must infect cells and use components of the host cell to make copies of themselves. Often, they kill the host cell in the process, and cause damage to the host organism. Viruses have been found everywhere on Earth. Researchers estimate that viruses outnumber bacteria by 10 to 1. Because viruses don\u2019t have the same components as bacteria, they cannot be killed by antibiotics; only antiviral medications or vaccines can eliminate or reduce the severity of viral diseases, including AIDS, COVID-19, measles and smallpox<\/em><\/p>\n Structure of the SARS-CoV-2 coronavirus<\/strong><\/p>\n SARS-CoV-2 is an enveloped virus with a positive RNA strand. The \u201ckey\u201d to enter the cell is found in the so-called \u201cspike\u201d proteins (S), which cover the virus envelope.<\/p>\n *Caption:\u00a0<\/b><\/em><\/p>\n S spike (peplomer) glycoprotein<\/p>\n M protein<\/p>\n Hemagglutinin esterase (HE)<\/p>\n Envelope<\/p>\n RNA and N protein<\/p>\n E protein<\/p>\n What does the Cuban Soberana-01 vaccine candidate consist of?<\/strong><\/p>\n There are different types of vaccines, from those that use the live attenuated pathogen, vaccines that use the killed (inactivated) pathogen, vaccines with toxoids, vaccines that are based on genetic technology (DNA or RNA), to many types of subunit vaccines (they use a part of the pathogenic agent\u2015antigen\u2015with a proven immunogenic capacity, that is, capable of inducing the immune response). The Cuban SOBERANA-01 vaccine candidate is in this last group.<\/p>\n It is logical to imagine that the success of a subunit vaccine depends to a large extent on the antigen that is chosen to produce it. In the case of the researchers from the Finlay Vaccine Institute \u00a0(IFV) who lead this project, they bet\u2015as they themselves have explained\u2015, after the structure of the virus was known in the scientific world, and doing a meticulous investigation, on the RBD protein<\/strong> (receptor-binding domain) found in the \u201cspike protein,\u201d the \u201ckey\u201d to enter the human cell.<\/p>\n *Caption: <\/strong><\/em><\/p>\n SOBERANA 01<\/strong> VACCINE CANDIDATE<\/p>\n PROJECT LEADERS<\/p>\n THE LEADERS OF THE SOBERANA 01<\/strong> PROJECT WERE THE FIRST VOLUNTEERS VACCINATED BEFORE STARTING THE CLINICAL TRIAL THAT BEGAN ON AUGUST 24, 2020.<\/p>\n Dr. C. Vicente V\u00e9rez Bencomo<\/strong><\/p>\n General director of the Finlay Vaccine Institute . Cuban scientist with a nationally and internationally recognized trajectory, he is the main author of the synthetic antigen vaccine against haemophilus influenza type b (Hib). He graduated as a chemical engineer from the Moscow Lomonosov Institute, State Doctor by the Orleans University (France, 1983), Honorary Doctor of the Canadian Quebec University in Montreal and Member of the Academy of Sciences of Cuba, among others. He received the Knight Order of the Honor Legion, the best known and important of the French distinctions conferred on men and women for extraordinary merits.<\/p>\n Dr. C. Dagmar Garc\u00eda Rivera<\/strong><\/p>\n Director of Research of the Finlay Vaccine Institute. Holder of a degree in Pharmaceutical Sciences from the Las Villas Central University in 1998. Researcher and university professor. Doctor in Sciences.<\/p>\n Yury Vald\u00e9s Balb\u00edn<\/strong><\/p>\n Assistant director of the. He forms part of the group of authors of the vaccine against haemophilus influenza type B and is part of the research project to obtain conjugated vaccines against streptococcus pneumonia. In 2016 he won the Annual Prize of the Academy of Sciences of Cuba.<\/p>\n ***<\/strong><\/p>\n Of the 30 vaccine candidates in the world that are in the clinical trial phase (WHO, August 20, 2020), 8 candidates are of the subunit vaccine type and only two, the Cuban and one developed by China, use the RBD protein, this is most likely due to the fact that its characterization<\/a> and studies on it are very recent.<\/p>\n *Caption:\u00a0<\/strong><\/em><\/p>\n Types of vaccines<\/strong><\/p>\n Viral vector<\/p>\n Subunit protein<\/p>\n RNA<\/p>\n Inactivated virus<\/p>\n DNA<\/p>\n Pseudoviral particles<\/p>\n What are the advantages of working with the RBD?<\/strong><\/p>\n The key and lock theory has been widely explained to understand the entry of the virus into human cells. Putting it in the simplest possible way: the SARS-CoV-2 virus, which causes COVID-19, has a protein in its envelope, the famous spike protein (S), that \u201cbinds\u201d to a receptor in human respiratory and digestive cells. Apparently the union between the virus and the cell is determined by a subunit of the S protein known as the receptor binding domain (RBD)<\/strong>, that would be the famous \u201ckey\u201d that opens the cell for the virus to enter and multiply.<\/p>\n The coronavirus that causes COVID-19 and the one that causes the disease known as SARS, bind to the same cell receptor, however, one of the factors that may be influencing the great viral replication observed in COVID-19 (greater than in SARS) is that this union is more efficient.<\/p>\n Therefore, the RBD protein plays an important role. As this is the active component of the Cuban vaccine candidate, if the preparation is successful, it will generate antibodies against RBD that will block this entry key to the cell and possibly neutralize viral replication.<\/p>\n *Caption:\u00a0<\/strong><\/em><\/p>\n ANTIGEN-ANTIBODY<\/strong><\/p>\n Receptor cell<\/p>\n Replication in host cell<\/p>\n VIRAL INFECTION<\/p>\n Antibody<\/p>\n Host cell<\/p>\n Receptor cell<\/p>\n NEUTRALIZATION BY ANTIBODIES<\/p>\n Now then, once this antigen was identified, it was necessary to produce it, purify it and test its ability to generate a protective immune response. RBD is a complex protein, which according to Dr. Belinda S\u00e1nchez Ram\u00edrez, Director of Immunology and Immunotherapy at the Center for Molecular Immunology (CIM), who led this part of the process, it is necessary to produce this protein with mammalian cell technology, in which CIM has more than 25 years of experience producing recombinant proteins for cancer therapy and the production of humanized monoclonal antibodies.<\/p>\n The CIM not only had to produce the RBD that the vaccine candidate would use, but also seven more recombinant proteins that would be used in analytical techniques necessary as part of the vaccine evaluation process and that Cuba could not buy.<\/p>\n This stage in the development of the vaccine candidate was possible because the CIM has the recombinant DNA technology necessary for the expression of complex proteins in mammalian cells and also has platforms for large-scale mammalian cell fermentation, complex protein purification and for evaluating the identity of recombinant proteins, which allow for the production of RBD that the country would need for a mass vaccination campaign.<\/p>\n In addition to producing the RBD protein, it is necessary to validate the quality of the immune response it induces, both in animals and in humans. This also requires highly specialized analytical techniques in which the CIM has long experience.<\/p>\n Other components of the vaccine<\/strong><\/p>\n However, this small molecule alone could not be a vaccine. These subunits (in this case RBD) must be \u201cpresented\u201d to the immune system and a stable formula must be achieved, which would achieve high immunogenicity and which, in addition, is safe and implies few associated undesirable effects.<\/p>\n That is why the Cuban scientists have explained that they used the conjugation between the RBD with a platform that has been widely studied by the Finlay Vaccine Institute. This platform, which seeks to \u201cpresent\u201d adequately the RBD to the cells of the immune system, stabilize the formula and enhance the immune response of the cells of the immune system, has been the outer membrane coat system of meningococcus and alumina; the basis of VA-MENGOC<\/a>, meningococcal BC vaccine.<\/p>\n The outer membrane coat of the meningococcal bacteria has been widely studied by the Finlay for many years as an enhancer of the innate immune response and, in fact, has been studied by the Institute itself as one of the pre-existing Cuban medicines in the fight against COVID-19 since the beginning of the pandemic.<\/p>\n Alumina, on the other hand, is the adjuvant (a word that comes from Latin and that means \u201cthat which assists, that helps,\u201d in vaccines it refers to substances or procedures that, incorporated into the antigen or injected simultaneously with it, make the immune response more effective) most recommended in the production of vaccines for humans, offers stability and increases immunogenicity with very few side effects.<\/p>\n The outer membrane-alumina coat platform, part of the Finlay Vaccine Institute\u2019s production line, is tested, standardized and guarantees production, in case the preparation is successful.<\/p>\n *Caption:<\/strong><\/em><\/p>\n SOBERANA 01 VACCINE CANDIDATE<\/strong><\/p>\n TYPE OF VACCINES<\/p>\n MAIN COMPONENTS<\/p>\n INVOLVED INSTITUIONS<\/p>\n IN CLINICAL TRIALS, ALSO:<\/p>\n KEY DATES:<\/strong><\/p>\n Having achieved, in 7 weeks, the design of a vaccine candidate and the production of lots of vaccines for the start of clinical trials is a great scientific achievement, and in addition to the will, intelligence and dedication of its creators and participants, it has been possible because Cuba has a powerful and undeniable biotechnological development and a pharmaceutical and health system with an experience that has made it possible to use its lines of research and production, the accumulated knowledge, in the solution of a serious global health problem, within the reach of very few biotechnology-pharmaceutical industry and health systems in the world.<\/p>\n Cuban medicines against COVID-19 (II)<\/a><\/p><\/blockquote>\n![\"\"](\"https:\/\/oncubanews.com\/en\/wp-content\/uploads\/2020\/08\/coronavirus-estructura-1.png\")
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