COVID-19 vaccine development pipeline gears up


22 February Irene Hartmann
Coronavirus: how the Chinese Sinopharm vaccine differs from Sputnik and Covishield.
It will be the third brand to arrive in Argentina and joins the other two. The arrival of a million doses is expected in the next few days. It is more expensive, but it also has its advantages.

Until Sunday it was circulated that this Thursday night the largest batch of vaccines would arrive in Argentina since the long-awaited stage of immunization against the coronavirus began: one million doses of the BBIBP-CorV vaccine, better known as Sinopharm, the name from the Chinese company that produces it, in collaboration with the Beijing Institute of Biological Products. This Monday, sources from the aeronautical sector explained to Clarín that Thursday seems a difficult goal, since at the end of this note there was no confirmed departure flight. But, delays aside and considering that the largest infectious disease specialists in the country indicate "do not hesitate and get vaccinated with whatever there is", it is worth reviewing the particularities of this drug.

It is that both Sputnik V and the Indian version of the Oxford-AstraZeneca (Covishield) use a technology - "platform", experts like to say - completely different from Sinopharm. As described by the infectologist and main adviser to the Government in the pandemic, Pedro Cahn (medical director of Fundación Huesped and who carried out the local study of this Chinese vaccine, for which 3,008 volunteers were recruited), “the Sputnik vaccine uses two types of adenovirus, a virus that causes colds. They made a genetic modification to those viruses and placed an antigenic element: the gene for the Spike protein. In this way, the body builds antibodies. In the case of Sinopharm, the Covid-19 virus was used, but dead, that is, inactivated ”.

There is a lot of talk about antigens. What are they? Jorge Quarleri, PhD in Biochemistry, expert "virologist" at the Institute for Biomedical Research in Retroviruses and AIDS (INBIRS) and Principal Investigator at Conicet explained it with accessible words. “An antigen is any substance capable of generating an immune response from the organism. To make an inactivated vaccine, the virus is multiplied in the laboratory and then purified. By means of a chemical treatment, it is inactivated in such a way as to nullify any possibility that this virus is viable: it will not be able to multiply and it will lose its ability to infect ”, he clarified. "Once inactivated, you get a bag of viral antigens. This is different from the vaccines that have been used so far, which immunize with a particular antigen, the coronavirus protein S," Quarleri said. The three experts consulted (and this includes Juliana Cassataro, a specialist in immunology, infectious diseases and vaccine development at the Institute for Biotechnological Research of UNSAM) agreed that the inactivated virus platform is "classic", and that it is used in several vaccines of the official calendar (such as the one that fights hepatitis A), since it is suitable, in terms of "safety", for all types of patients, including immunosuppressed and pregnant women. Another advantage is the conservation, which facilitates all the logistics of vaccination: it is well maintained between 2C and 8C, that is, the temperature of a common refrigerator. As for the doses, it does not differ from other vaccines: they are two, identical, separated by three weeks.

The against? The cost. Before we get to that point ... is it better to get a coronavirus vaccine that has a lot of antigens?
First, Cahn said, "in terms of the perception of the recipient, there are no differences." Although the results of the local study with this vaccine are not ready, “international data indicate an efficacy of almost 80%. In addition, the adverse effects are minor - some fever, perhaps, and some pain at the injection site - and the main thing is that it works by preventing serious forms of the disease. With these words, Cahn referred to a central question: there are still no studies that prove that any vaccines are capable of completely preventing the spread of coronavirus. On the other hand, it is known that the chances of having severe symptoms in the face of the disease decrease.

These are subjects under study and, just as the famous paper of phase 3 of the Sputnik vaccine was long in coming, there are also missing publications of that phase of the Sinopharm vaccine, beyond the fact that the ANMAT recommended it for emergency use and the Ministry of Health authorized it. For Juliana Cassataro, some optimistic hypotheses can be used regarding the developments with inactivated virus: “The Chinese vaccine, unlike the others, has all the coronavirus antigens. From an immunological point of view, in the long term, these types of platforms could be less susceptible to the changes that the virus naturally makes. But you have to wait. For now it is not really known ”.

The cost of a supposed benefit is clear. “The development of these vaccines takes longer, which is why pharmaceutical companies often choose adenovirus. To make an inactivated virus, a plant is needed to manufacture live virus, with all the safety conditions, which makes production much more expensive, especially with these very dangerous viruses. That is why they are more expensive vaccines ”. Of the between $4 and $10 dollars per dose, we reached an agreement that is around $20 dollars per dose, after a reduction that Argentina achieved.

Maybe it is worth the expense. According to Quarlerí, "the only neutralizing antibodies are those that the body develops against protein S, but using an inactivated vaccine will achieve antibodies against other viral components, whose biological significance we must still elucidate in terms of protection." In addition, there is another immune response of the body that could be amplified with this type of vaccine: the immune response mediated by T lymphocytes, "which is the body's cellular response. The immune response could be prepared to recognize in a more expanded way the presence of infected cells ”.

However, the expert said, "as with all vaccines, you have to be cautious: wait for the end of phase 3 and do pharmacovigilance for a long time."


23 February 2021....behind a paywall
Lacalle and his ministers celebrated between applauses the making of a "goal" with the vaccines. This is the chronogram.
....Lacalle informed his cabinet that between Thursday evening and Friday at dawn will arrive the first 192,000 doses of Sinovac, and that as of March 1st they would begin to be applied to workers in the education field, police and firemen in activity, military in activity and workers of the INAU (Instituto del Niño y Adolecente), as long as they are 60 years old or younger. On March 15th Sinovac would increase the delivery to another 1,558,000 doses.

On the advice of the National Advisory Committee on Vaccination, the health personnel and senior adults would have to wait a few days more for the arrival of the Pfizer vaccine, from March 8th on. Lacalle explained that if the time lapsed between the arrival of the Sinovac vaccine and that of the Pfizer was more "extended", it would have been decided to vaccinate the health personnel with the one which would arrive first. "But because the time between the arrival of one and the other was about 10 days, it was good to wait on the arrival of the Pfizer to vaccinate the health personnel".

Pfizer, that in total will supply 2 million doses, delivering 468,000 beginning March 8 through April 26, about 50 or 60 thousand per week. The Coronavac as well as the Pfizer require a second dose in 28 days. To comply with those dates, the follow-up injection appointment would be reserved automatically.

The gov't is waiting as well for the confirmation date that the vaccines will arrive from the Covax Fund. The authorities expect that sometime in March will arrive the first delivery of 180,000 doses of AstraZeneca, with which will advance in the vaccination of senior adults. With those numbers in sight, Lacalle Pou said they expect a "continuous and fluid" process of vaccination "without dead time" (lapses without stock of doses). "It was a concern, but if we calculate 30,000 doses per day, 6 days per week, our projection is that there will not be any "down time", he affirmed.

Behind closed doors, the President emphasized that he does not approve of making a "show" of the arrivals of the vaccines, according to participants at the meeting....

....Lacalle Pou proposed during the meeting the possibility of advancing this year with the idea of a sanitary passport to enable the entry of those with proof of having antibodies of the disease. The President clarified that it is too early to set a deadline. Cabinet members pointed out to El Observador that it would be a later phase, once a good portion of the Uruguayan population was vaccinated, or at least those who do not want to do it have had the possibility to be vaccinated. "The sooner it can be opened to those who eventually are vaccinated, or those which have had the illness and have an antibody test, could arrive without the need to quarantine. We are going to go on course to the opening of borders and activities", said Lacalle Pou in a press conference prior to the meeting....


23 February Lorena Bermejo
BioCubaFarma reported that in 2021 it could produce 100 million doses.
Final steps for Soberana 02, the first Latin American vaccine against coronavirus.
"As of the second semester, we will be able to immunize the entire population, and also provide doses to the countries that require it," said the director of the state-owned company, Rolando Pérez Rodríguez. A few days after starting the last phase of the clinical trial of Soberana 02, which has all the cards to be the first fully developed vaccine in Latin America, the Cuban scientific community confirmed that it expects a production of 100 million doses for this year. "It is about sharing with the world what we are, the answer that Cuba can give to the problem of the pandemic," reflected Rolando Pérez Rodríguez, doctor in Biological Sciences and Director of Science and Innovation of the company BioCubaFarma, in dialogue with Página / 12. "We will be able to vaccinate the entire population before the end of the year, but we will also have production capacity to offer it to other countries that demand it," said the specialist. At the end of March, another of the Cuban vaccines, Abdala, developed by the Center for Genetic Engineering and Biotechnology (CIGB), joins the third phase of clinical trials.

BioCubaFarma, founded in 2012, is a state company that brings together 32 companies from the biotechnology sector and the Cuban pharmaceutical industry. With 20 thousand workers, it exports more than 300 products to 50 countries, and has to its credit about 700 medical records. Since the coronavirus began to spread around the world, its resources have been focused on managing the pandemic. On the one hand, the development of vaccines -four of them in an advanced stage-, and on the other, the production of drugs to address infections and efforts to increase diagnostic capacity, which resulted in the achievement of one of the The lowest fatality rates in the world - with only 300 deaths in total until this Monday - despite the increase in infections in recent weeks, when from 12 thousand cases, Cuba had more than 45 thousand.

-Why develop your own vaccine? - Several reasons converge. In Cuba, one of the strengths of the biotechnology industry is precisely the development of vaccines. Furthermore, from the moment in which potential agreements began to be made in the rest of the world, at very high prices, to acquire vaccines that did not yet exist, we realized that they were not going to reach it. For us, the economic blockade of the United States, especially in this last period -during the government of Donald Trump-, complicates access to certain products and we cannot always reach the most suitable supplier, this added to the fact that we are experiencing a global shortage of certain supplies, such as syringes. Despite this difficulty, we made progress. The idea of the vaccine is to be able to show that just as Cuba needs the rest of the world, it can also contribute a lot.

So far, of the dozens of investigations to develop an antigen against the coronavirus, four Cuban vaccines are underway. Two are in charge of the Finlay Vaccine Institute (IFV), Sovereign 02, with 150 thousand doses ready for the start of the third phase of clinical trials, and Sovereign 01, still in the first stage of human trials. The other two are in charge of the CIGB: the Mambisa, a novelty due to its nasal delivery characteristics, and the Abdala, which begins the last stage of large-scale human trials at the end of March. The four vaccine candidates use the RBD protein as antigen, which binds the viral body with the human cell. For both Abdala and Sovereign 02, the specialists foresee the application of three doses, with an immunization schedule of 0-28-56 days, although for the first they still evaluate a shorter schedule, of 0-14-28 days.

-How is Sovereign 02? -The most important thing is that it is a secure platform. It has not shown any adverse effects so far. It is a conjugated subunit vaccine, based on the RBD protein, which is a domain -subunit- of protein S, from the term “spike” (Spike) in English. RBD, binding to the receptor, allows the virus to enter the human cell. The vaccine inhibits this binding, generating neutralizing antibodies. We chose this type of vaccine based on recombinant proteins because we have experience with the same technology in previous research, against other viruses, and the capacities not only to investigate, but to take production to an industrial scale.

-When will it begin to apply massively? -First we have to go through phase 3, which, as there is more incidence of the virus in the country, although this is bad news for society, facilitates the clinical study. For this stage we manufacture 150 thousand doses. In parallel, we are going to increase the evidence of effectiveness with trials in areas that we know have more epidemiological complexity due to population density. And in the meantime we are advancing in protection, immunizing thousands of people. For the month of June, the results will be in, for the registration and massive use of the vaccine, and from the second semester we will be able to immunize the entire population, and also provide doses to the countries that require it. The productive capacity that we have for this type of vaccine is really great, which uses only one fifth of an antibody. For this phase of the clinical trial, IFV - under the orbit of BioCubaFarma - signed an agreement with the Pasteur Institute of Iran, to send a dose contingent of Sovereign 02 as part of the vaccine trials. Iran is one of the Middle Eastern countries most affected by the coronavirus. The vaccination campaign with the Russian Sputnik V vaccine began earlier this month.

-Will Sovereign 02 arrive in Argentina? -I dont see why not. It is still premature to talk about distribution, because it is necessary to see how the vaccine is registered and which countries accept the authorization of the local entity. There are many interested parties in the region, but no particular agreements have been reached yet.

Cuba has a long tradition in biotechnology: it was the first country to eradicate polio, developed the first vaccine against meningitis in the late 1980s, and managed to produce its own vaccine against Hepatitis B in 1990. What was it? the key to vaccine development? -Experience in other investigations allowed us to advance with some speed, but it was also the product of coordination between the companies and the Scientific Pole, we always work in an integrated way, in a productive chain that enhances and accelerates projects. In the case of the two vaccines that are on the horizon -Soberana 02 and Abdala- those in charge of large-scale production are the National Center for Biopreparations (Biocen) and the Aica Laboratory, but always in coordination with the other institutions that were part of the investigation.

-In addition to the four vaccines that are in an advanced stage, are there others in progress? -Yes, we are in favor of not stopping the investigations. There are already new strains of the virus that may be resistant to vaccines, if we continue to investigate, we can prevent the problem. There are other developments that we continue to work on at the preclinical level, vaccines that could be recombined to combat the most resistant strains. We are also beginning the second phase of the trials of Sovereign 02 in the pediatric population, which in Cuba is considered from preschool to 19 years of age, but now we must concentrate on the most urgent thing, which is to advance rapidly with production in order to begin massive vaccination.


24 February 2021..10:35pm..Bloomberg News
A vaccine developed in Wuhan, the birthplace of Covid, showed 72.5% efficacy.
Sinopharm Group Co.'s second coronavirus drug, developed by a subsidiary based in the Chinese city, has a lower effectiveness rate than its first version, but above the approval threshold for general use.

Sinopharm Group Co. reported that its second coronavirus vaccine, this time developed by a Wuhan-based subsidiary, is 72.5% effective in preventing COVID-19 in people, less than its first vaccine, but for Above the approval threshold for general use. To increase the chances of success, the company's vaccine subsidiary, China National Biotec Group (CNBG), launched the development of two treatments independently at its research institutes in Beijing and Wuhan.

The first vaccine, developed in Beijing,
showed an efficacy in the prevention of covid-19 of 79.3% in people. It was approved for use in the general population and has been widely distributed in China and other parts of the world. The company filed for conditional approval of its second vaccine with the China National Medical Products Administration on February 21, according to a statement posted on the website of the Wuhan Institute of Biological Products Co., a CNBG subsidiary.