Soberana is Cuba’s, the first candidate vaccine against COVID-19 in Latin America and the Caribbean

Centro Nacional de Cirugía de Mínimo Acceso de Cuba

Cuba. A vaccine that exemplifies the development of Cuban science; that places us on the level of economically advanced countries; that honors Comandante en Jefe Fidel Castro Ruz, the principal architect of the country’s biotechnology sector. This is what Soberana is, the first Cuban candidate vaccine against COVID-19 authorized for testing in clinical trials.

To discuss the process of its development, entering the first phase of clinical trials the end of August, the results of which should be available early next year, and the accomplishment achieved by the joint work of a large group of Cuban scientists, leaders of the Finlay Vaccine Institute (IFV), project researchers, and the assistant director of the State Center for Quality Control of Medications (Cecmed), appeared on Cuban television’s Mesa Redonda program.

This is vaccine candidate number 30 – the first in Latin America and the Caribbean – to receive authorization for clinical trials, among the more than 200 under development around the world, noted Vicente Vérez Bencomo, director of the Finlay Vaccine Institute. He emphasized that, given the lack of knowledge of the previously unknown virus, it was impossible to predict how quickly a COVID-19 vaccine could be developed, since projects of this kind generally take years.

Nevertheless, he said, over an unprecedented short period of time, much information on SARS-COV-2 has been generated around the world, and, again exceptionally, access to these scientific studies has been made available free of charge.

He recalled that, in the beginning, the first option to develop a vaccine was basically to cultivate the virus, inactivate it, and put the material to use, the well-known procedure used to develop vaccines of this nature. How this would work was not known precisely, but by this past January, the world was moving forward with the first efforts using traditional methods.

Subsequently, Vérez continued, after the virus’ genome mapping was completed in March, a group of vaccine projects based on this genetic information began to advance more rapidly, although reservations about them emerged.

Plus, cultivating the virus in large quantities implies a number of risks in terms of the production process, making the use of this technical approach practically impossible for the Cuban industry.

By April, as more was known and understood about the behavior of the virus, it was possible to identify similarities with others for which vaccines had been developed, making Cuba’s previous experience in such work applicable. Thus, another option was available to Cuban institutions, allowing some phases of the process to be shortened, Vérez explained.

As studies advanced, he noted, the world’s regulatory system began to adapt to the pandemic and established time frames were shortened, without foregoing security requirements for the development of a vaccine.

The Finlay director recalled that a meeting between researchers and the country’s highest leadership in May was very stimulating, with emphasis placed on the importance of Cuba having its own vaccine to guarantee our sovereignty.

Vérez went on to explain that the development of a vaccine involves four fundamental phases. The first is the pharmaceutic stage that includes trials in animals, testing for toxicity and other elements, to conclude with approval to begin clinical trials.

Next, he continued, phase one of the clinical trials requires showing, in a small group of subjects, that the product is safe. In phase two, with a broader group of volunteers, the goal is to see if the candidate vaccine produces an adequate immune response, and finally in phase three, its effectiveness in preventing the disease is determined.

He emphasized that Cuban scientists have only reached the first milestone on a long, steep path, but have done so in just three months, and in the case of the new coronavirus, this is a critical phase.

He noted that China is the country working on the highest number of candidates, followed by the United States, Britain, Russia, Germany, and others, but Cuba’s is the first in Latin America and the first in a poor country – poor in material resources but rich in spirit.

WHY SOBERANA?

According to Vicente Vérez, there are many versions as to how the vaccine’s name emerged; but the people named it Soberana (Sovereign), he said, based on the pride we all feel in this accomplishment of Cuban science.

And why the dedication to Fidel? The institution’s director referred to his own humble origins, and his gratitude, since it is thanks to the Revolution that he became a scientist.

For all the project’s investigators, he insisted, this is a very important achievement, but to paraphrase the musicians who wrote “Valientes,” this is not heroism at all, but rather a kiss for the homeland, nothing more.

A QUESTION OF SOVEREIGNTY

For his part, Yury Valdés Balbín, IFV assistant director, reported that after representatives of the country’s scientific community met with the President of the Republic, Cuban experts re-designed the entire strategy which was being followed to that point, with the focus on shortening the time required for each phase in the development of a COVID-19 candidate vaccine.

In his contribution to the conversation, Valdés explained how the feasibility of this accomplishment was envisioned, that is reaching the current stage in only three months, and the importance of launching such as ambitious project on the island.

His explanation included four key challenges to be overcome along the path to what we know today as Soberana. He referred to different scientific tests the team involved was obliged to face, among them he highlighted the identification of the protein RBD as the project’s principal antigen. He likewise noted the employment of platforms previously established to advance the process, stating that this has become a common practice around the world in an effort to speed up development of a COVID-19 vaccine, given the global impact of the illness caused by the new coronavirus.

As the third key to success, Valdés noted the application of new knowledge in real time, and the challenge this method implies for the scientific community working to contain the pandemic. Finally, he cited as the fourth key element the articulated action conducted through alliances between different institutions, highlighting, in this case, the collaboration of the University of Havana and the Molecular Immunology Center with his institution.

In this regard, he noted that the alliance did not emerge for the purpose of this particular project, but rather that joint work underway was re-directed to focus on a possible vaccine, given the health emergency created by COVID-19.

He additionally emphasized the contribution of the state enterprise group BioCubaFarma and other biotechnology centers in the country.

To give each one the credit they deserve, in what is undoubtedly one of the most significant achievements of Cuban science, Valdés used the metaphor of a puzzle to show how every single man and woman involved in the task played an important role in the project that is giving the Cuban people hope.

He made clear that, although the conception of the project was expedited, no established stage was skipped during the process thus far, since the initial design, and outlined the many different steps taken by researchers to date.

At another point during the presentation on Soberana, Belinda Sánchez Ramírez, director of Immunology and Immunotherapy at the Molecular Immunology Center (CIM), described the scientific contribution of this institution to the vaccine project making news these days.

She reported that the CIM took on the responsibility of producing the complex protein RBD, the antigen identified at the Finlay Vaccine Institute as key to creating the vaccine. Thus, she said, the Center joined the process, contributing its 25 years of experience in using mammal cell technology, which is the established method of producing this antigen.

Sánchez emphasized that the CIM has the capacity to culture mammal cells on a large scale to produce this protein, and is prepared to produce the quantities of RBD needed to meet national demand for the vaccine.

A SCIENTIFIC IDEA IN A DOSE OF VACCINE

The director of research at the Finlay Vaccine Institute, Dr. Dagmar García Rivera, explained that reaching this point has been a challenge, since there was no knowledge of certain elements of the disease, requiring scientists to review every piece of information on the subject that emerged over the past few months.

Fortunately, she added, a great deal of information has been generated in a short period of time and the international community has been afforded access free of charge.

This allowed Cuban scientists to take advantage of new knowledge to develop a good design for our candidate vaccine, she said, and take the RBD route, “a known protein that we have the capacity here to fully characterize.”

She explained that Soberana is a sub-unit vaccine and explained the combination of this vaccine with one developed to prevent meningitis, in use for over 30 years on the island, with proven effectiveness and safety in several age groups, noting, “The idea was to create a vaccine based on existing platforms, to shorten the time required.”

Dr. García reported that seven days after the first dose was administered in rats, the level of RBD antibodies had risen, even more apparent 28 days later, explaining, “The presence of antibodies seven days after the vaccination in animals is a distinctive characteristic and probably attributable to the immune response strengthening ability of the external membrane’s vesicle, in which we formulated the vaccine.”

She added that the clinical trials began with the recruitment of participants and the first vaccination on August 24, emphasizing that the selection process conducted by a medical team was rigorous and involved a written agreement signed by the 676 volunteers, along with the commitment to a two-month follow up period.

The doctor concluded her remarks calling for social responsibility, emphasizing, “At this moment, Soberana needs the support of the entire people.”

CONTROL, APPROVAL & SUPPORT FROM CECMED

The authorization for clinical trials of the candidate vaccine Soberana approved by Cuba’s State Center for Quality Control of Medications, Equipment and Devices (Cecmed) provides unquestionable evidence of the scientific rigor involved in the development of a Cuban vaccine to prevent COVID-19.

This prestigious institution is charged with promoting and protecting public health, via a regulatory system capable of guaranteeing timely access to a supply of safe, effective, quality products and accurate information on their rational use, and in this capacity, certified with its approval the merits of the vaccine project identified as FINLAY-FR-1.

Led by the Finlay Vaccine Institute and the Molecular Immunology Center, both affiliated with the state enterprise group BioCubaFarma, with the collaboration of the University of Havana’s Chemical and Biomolecular Synthesis Laboratory, Cuban scientists have satisfactorily completed the pharmaceutical phase of the vaccine development process, with pre-clinical trials in animals.

Engineer Yaquelín Rodríguez Valdés, Cecmed assistant director, explained that this past January, as Cuba was preparing to confront the pandemic, the regulatory agency was called upon to participate in coordinating the country’s innovation committee, allowing for its timely participation, from the very beginning, in development of the vaccine.

She emphasized the great advantage Cuba has in its strong pharmaceutical and biotechnology industries, along with an internationally recognized regulatory body.

Among the facts that confirm this reality, she mentioned the Pan American Health Organization’s authorization of pre-qualification for Cuba’s recombinant anti-hepatitis B vaccine, “which allowed us to demonstrate that not only were our productive processes strong, but backed by a regulatory authority as well, leading to our becoming the first vaccine regulation system in Latin America to be granted competent authority, granted by the World Health Organization (WHO), which has been maintained to date,” she reported.

Rodríguez additionally cited WHO’s recognition in 2010 of Cedmed as a Level 4 Regulatory Authority of Reference (the maximum status granted), another confirmation of the agency’s competency in certifying medications, to which in 2017 the authority to control vaccines used in the country was added.

She noted among the institution’s strengths its broad knowledge of the Cuban pharmaceutical industry; the rigor with which products, best practices, and clinical trials are reviewed, prior to their certification, or authorization in the case of clinical trials, requirements for which are obligatory and must be met before the product is registered.

The Cedmed assistant director emphasized that her institution will continue supporting the clinical trials, as the Finlay will be submitting ongoing partial reports for their consideration and the final report on findings in subsequent phases of the process.

(Infografía)
PREVENTATIVE VACCINES PRODUCED IN CUBA

Anti-Hepatitis b

institution: Genetic Engineering & Biotechnology Center (CIGB)

Anti-Meningoccus bc

institution: Carlos J. Finlay Pharmaceutical Laboratory

Anti-Rabies

institution: Carlos J. Finlay Pharmaceutical Laboratory

Anti-Tetanus

institution: Carlos J. Finlay Pharmaceutical Laboratory

Anti-Diphtheria & Tetanus

institution: Carlos J. Finlay Pharmaceutical Laboratory

Anti-Diphtheria, Tetanus & Whooping Cough (dtp)

institution: Carlos J. Finlay Pharmaceutical Laboratory

Trivalent Anti-leprosy

institution: Carlos J. Finlay Pharmaceutical Laboratory

Tetravalent dtp-hb (Trivac-Hb)

Against diphtheria, tetanus, pertussis & hepatitis B recombinant

institution: CIGB

Pentavalent Heberpenta

(combined vaccine against diphtheria, tetanus, hemophilic influenza type B & hepatitis B) recombinant

institution: CIGB

Anti-Typhoid

(to prevent typhoid fever)

institution: Carlos J. Finlay Pharmaceutical Laboratory

Anti-Hemophilic influenza type B

institution: Carlos J. Finlay Pharmaceutical Laboratory, CIGB & National Bio-preparations Center (BioCen)

MILESTONES IN CUBAN BIOTECHNOLOGY

Immunization Program

Created in 1962, as part of political, economic and social transformations initiated in 1959, after the triumph of the Revolution

Immunoassay Center

Inaugurated September 7, 1987, specialized in the development of diagnostic systems. Cuba’s unique SUMA (Ultra-micro Analytical System) devices were designed here, to conduct broad testing for congenital defects and today used for a variety of diagnosis, including COVID-19.

Introduction of Oral Polio Vaccine

In 1962 Cuba became the first country to eliminate poliomyelitis

National Center for Scientific Research (cnic)

Founded by Presidential resolution, July 1, 1962, to conduct scientific investigations

Finlay Vaccine Institute

Founded in 1991 and devoted to the production of vaccines, creator of the anti-leprosy vaccine and producer of many other standard vaccines.

National Center for Production of Laboratory Animals (Cenpalab)

On October 5, 1982, Fidel approved the Cenpalab project and in May of the following year, its construction began. Responsible for the important task of supplying this indispensable resource to research institutions, including feed and veterinary vaccines.

National Biopreparations Center (BioCen)

Founded in 1992. Manufactures products developed in other research centers, including the hepatitis B vaccine, culture media, allergens and anti-anemia drugs. Investigating new culture media, the production of hydrolyzed proteins, and allergy remedies.

Genetic Engineering & Biotechnology Center (cigb)

Founded July 1, 1986, by Fidel Castro Ruz. Combines research with experimental development, the production of pharmaceuticals and their commercialization.

Molecular Immunology Center

Founded in 1994, by Fidel Castro Ruz, as a comprehensive biotechnology institution devoted to research, development, production and commercialization.

Pharmaceutical Chemistry Center

Founded April 1, 1989. Conducts scientific-technical research to support development of bio-active systems for the elaboration of medications.

-Recombinant thrombotic estreptoquinesa, produced by cigb, to be used in treating infarto agudo de miocardio.
-Recombinant Human Interferon Alfa 2b, created by cigb scientists in the late 1980s, and currently one of the medications most successfully used to treat

covid-19.
-Peptide cigb-258, able to detain the process of pulmonary inflammation, that often proves fatal for COVID-19 patients in serious or critical condition

-Peptide cigb-325, contributes to controlling the deterioration of COVID-19 patients

SOBERANA

PURPOSE: Prevent COVID-19

AGE GROUP UNDER STUDY: 19-80 years of age

SAMPLE SIZE: 676 subjects

PRINCIPAL PROMOTER: Finlay Vaccine Institute

PARTICIPANTS: healthy volunteers

REQUIREMENTS FOR PARTICIPATION IN SOBERANA CLINICAL TRIALS

–Signed informed consent agreement

–Aged 19-59 or 59-80 years

–Body mass index between 18 and 29.9 kg/m2

SOBERANA CLINICAL TRIALS TIMELINE