News published in different media has ensured that Mambisa, the Cuban vaccine candidate that is applied nasally and the first of its kind to start clinical studies in humans in the world, could cut off the transmission of Sars-CoV-2. How would do it? Will modern science, and specifically this contribution from Cuba, finally manage to deal a radical blow to the Covid-19 pandemic? Doctor in Biological Sciences Gerardo Guillén Nieto, director of Biomedical Research at the Center for Genetic Engineering and Biotechnology (CIGB), speaks about these and other questions.
—Doctor Guillén, what is Mambisa?
—A vaccine candidate based on the nasal route as an immunization route, through which the virus enters the body. Its main attraction is that a vaccine capable of inducing a strong response at the level of the nasal mucosa, of the nasopharyngeal mucosa, can prevent colonization of the virus and thus reduce transmission between people. In other words, it not only protects against the severity of the infection and the symptoms —demonstrated effectiveness with injectable, systemic vaccines—, but it also reduces transmission, contagion. That is its main advantage.
“The vaccine consists of the same antigen or protein component that Abdala has, plus another recombinant protein particle obtained by biotechnological methods. Unlike Abdala, which is achieved by a yeast fermentation process, this is achieved by the Escherichia coli bacteria, also by fermentation, and is the component responsible for immunopotentiation or adjuvation or the ability to induce a powerful immune response through the in which it is administered”.
Doctor Guillén Nieto comments that this platform was developed by the CIGB in 2015, when it registered a vaccine that is also administered by the nasal route, therapeutic in this case, against chronic Hepatitis B.
“It is the first vaccine in the world against a chronic infectious disease, and the first against a chronic infectious disease that is administered by the nasal route, whose technological platform we used for the development of Mambisa.”
He assures that Cuba is a leader in this technology, thanks to the fact that it has the aforementioned immunopotentiating adjuvant. “Even the magazine Science in July of last year recognized that there were only seven vaccines that used the nasal route – and the only one with the recombinant biotechnological method is Mambisa –, among more than two hundred coronavirus vaccine candidates that there were at that time in growth. The others were live vector or mRNA vaccines, which are also used by injection. Now there are eleven vaccine candidates that are already in clinical evaluation, also with these various technological platforms.”
Mambisa and its studies in phases
Clinical studies with the vaccine candidate Mambisa have shown the safety of the drug, and also that 78 percent of those who received it (not previously vaccinated or infected) developed a mucosal response.
According to Dr. Guillén, Titular Academician of the Cuban Academy of Sciences since 2012, in correspondence with the advance of vaccination and the epidemic, the Cuban scientific team was redirected the vaccine candidate Mambisa to its use as a booster dose, “Because the vast majority of the island’s population had already been vaccinated, and also a percentage had been convalescent (had been infected with Sars-CoV-2).
In tune with this reality, “we are developing two clinical studies, one of them -which is already in the final evaluation of the samples obtained from the two thousand two hundred and twenty volunteers-, with people who were previously vaccinated with Abdala and received three doses of immunized with this vaccine and five and a half months later they were boosted with Mambisa or Abdala, half with Mambisa and half with Abdala.
And the other, which is already in Phase II, is based on the application of a dose with Mambisa or Abdala as a booster in individuals who have been exposed to the virus (convalescents) who had not been vaccinated before or after becoming infected. explained Dr. Guillén.
“In Phase I we included one hundred and twenty individuals, three groups with Mambisa and one group with Abdala: thirty people in each group. There were three Mambisa groups as we tested three different nasal delivery devices, and all met the success criteria. Therefore, the device that we select to continue towards Phase II is the one that we have the capacity to produce in the country, in charge of the Cuban Neuroscience Center.
“Now we are developing Phase II in four clinical centers nationwide. The inclusion of volunteers has been very difficult, more complex, and a little slower because the selection criterion is that they be convalescent people who have not been vaccinated before or after, when there is already a high percentage of the population in the country that has been vaccinated.
In order to reach a greater number of these volunteers, the vaccines offered for the study are Mambisa and Abdala without thiomersal, which has made it possible to include those allergic to this substance who had not had the opportunity to be vaccinated in the early stages.
This investigation —specifies Doctor Guillén— includes two groups: the one from Mambisa in Phase I with the device that we can produce nationally, and one from Abdala. It should include just over a thousand volunteers, stratified into those under sixty (already complete) and over 60 years old (about 150 to be included), from 18 to 80 years of age.
The scientist also explains that at this time the Hermanos Ameijeiras hospital is being studied; the Raúl Sánchez polyclinic, in Pinar del Río, where they have worked very well in recruiting volunteers. Also the Amalia Simoni hospital, in Camagüey, and the Saturnino Lora, in Santiago de Cuba, which will receive participants from Granma, for example. In Camagüey, volunteers from Ciego de Ávila, Las Tunas and Sancti Spíritus have been treated. In the Ameijeiras, Artemisa and even Matanzas”.
—You said that Mambisa is a leading vaccine. Is it because it is the most advanced?
—Yes, first because we use the technological platform of proteins by subunits, of recombinant proteins as it is called. They are proteins of more than ninety-nine percent purity, and defined proteins.
— Purity?
— Yes. It means that the vaccine has no other contaminants, which makes it a very reliable platform, which is mastered, because it has already existed for more than thirty years at the CIGB. For the Hepatitis B vaccine that we produce (it was obtained in 1991) we use this same platform, and the therapeutic vaccine that I mentioned was registered in 2015. In other words, it is a platform that is widely used in the world, and in practice it has been shown to be very safe. The Hepatitis B vaccine is given to infants within the first twenty-four hours of birth. In addition, it has already been shown in the clinical studies of Mambisa that the adverse reactions are mild, not serious, and do not require hospitalization. All this facilitates its progress in the regulatory aspect, so that it can be registered.
“On the other hand, the other vaccines that are in clinical studies in the world use very novel platforms, mRNA platforms, live viruses, with which care is required in terms of safety.
“These same platforms used as injectable vaccines have more adverse reactions, even serious ones; therefore, more precautions must be taken because the nasal route of administration is more likely to cause neurological damage, which has been one of the limitations for the development of nasal vaccines.
“Our platform does not use neurotoxic components, which is an advantage to be able to hope that, once the clinical studies that are underway are completed and the final reports have been obtained, they can be submitted to the regulatory authority and obtain authorization for emergency use. of the vaccine candidate Mambisa”.
—So, does this technology developed at the CIGB make the Mambisa course viable?
—The technology and the results that are being obtained, because in Phase I, for example, all the groups evaluated met the success criteria of the vaccine candidate. And in the studies that we are evaluating as a booster dose, antibody titers are also increased. So we are demonstrating the effect of the vaccine and its safety. These are the elements that are evaluated to obtain the emergency use authorization. And as for the production system, good production practices, consistency of production, stability of antigens.
“Furthermore, the main protein component of Mambisa is the same as that used in Abdala —which already has its emergency use authorization and is already produced on a large scale—, and the immunopotentiator, the other protein component, is also part of the Hepatitis vaccine registered in 2015 and which is also approved”.
—But, would they need to do a Phase III?
—No, in this case there is no Phase III because Phase III would imply having a non-immunized control group or with a placebo, and that control group is impossible once the entire population of the country is vaccinated.
“On top of that, we are talking about an indication as a booster dose. There can be no control in that sense. It is about demonstrating its safety and that it achieves the objective of increasing the immune response (that is, both the antibody titer and the functional capacity of these antibodies) and this is achieved with a Phase II, which includes more than two thousand volunteers in one of the studies mentioned above and more than a thousand in the other”.
In this regard, Dr. Guillén Nieto, Full Member of the Cuban Society of Immunology since 1996 and Honorary Member since 2012, explained that the Phase I, II, III study classification, although still used because it is very graphic, is archaic.
“Clinical trials can no longer be narrowed down so sharply; there are, for example, proof of concept, initial evaluation, safety clinics and signs of response, of effectiveness. However, that effectiveness is evaluated in different ways. In our case, we are talking about definitive clinical studies to obtain registration”. (Taken from Cuba in Summary.
Source:
Source: Taken from Cubaperiodistas. Flor de Paz. March 6, 2022. Available at
https://www.cubaperiodistas.cu/index.php/2022/03/pureza-y-eficacia-de-mambisa-la-primera-vacuna-nasal-anticovid-i-parte/
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