Text extracted from the interview with Dr. Antonio Condino, available on our Youtube channel.
Dr. Antonio Condino is a well-respected professional and known name the among academic and scientific field. He is an Immunology professor at the Institute of Biomedical Sciences at USP, director of the Jeffrey Modell Center for Immunodeficiency in São Paulo, and president of the Department of Immunology at the Brazilian Society of Pediatrics.
Let's talk about the mechanism of action of vaccines. A vast number of vaccines are in development, some advancing faster than others. How are the mechanism of action of these vaccines (that are currently available in Brazil and in the world) different?
Dr. Condino: Indeed, there are many vaccines in development, some of which are already in practical application, and I'm going to focus exactly on those that are the best known and that have a perspective of use here in Brazil. I'm going to divide into the following groups: RNA vaccines, inactivated viral vector vaccines, protein vaccines, and inactivated coronavirus vaccines. So, common denominator between all of them is that it doesn't exist, we don't have any live attenuated virus vaccine, so nobody is taking attenuated corona virus vaccine and taking the risk of catching a vaccine infection.
That kind of problem doesn't exist. This is the first clarification, and it's important to talk about it right away from our perspective of fighting fake news. There are messages circulating on the internet talking about these things and this is a lie, there is no live virus vaccine.
RNA Vaccines – they basically carry a genetic code of protein S, the Spike protein of the coronavirus that the virus uses to penetrate our cells and multiply in our body. It uses the Spike protein, binds to the ACE2 receptor, and penetrates in our cells. While in there, it multiplies and causes the disease. The RNA only encodes the piece of this Spike protein, so that RNA is packaged in a polyethylene glycol liposome and the vaccine is prepared in an intramuscular injection. When injecting it (inside muscle cells) this polyethylene glycol liposome releases the RNA sequences that encode the Spike protein, this RNA uses our genetic transcription machinery and generates the Spike protein, and this is released from our body, then taken up by the cells of the immune system. The sequence is: the cells are antigen presenters, they take up this protein S, they present it to the T lymphocyte, which is a type of white blood cell, the T lymphocyte stimulates the B lymphocyte, which produces the antibodies. Therefore, it's a way to induce the immune system of the vaccinated person to produce antibodies that neutralize the Spike protein. With that, the antibodies create a barrier against the penetration of the virus in our cells. So there, the virus does not enter, the antibodies block it. Viruses cannot cause infection because they cannot enter our cells. This includes Pfizer's vaccine and Moderna's vaccine.
Virus vaccine by inactivated viral vector – these are adenovirus, which cause common cold. This virus receives an insertion of the genetic sequence of the Spike protein, the same Spike protein as the previous one. Therefore, it is a common cold virus, genetically modified to express the Spike protein. It is inactivated, inside the lab, so it doesn't cause infection. What happens? Instead of using the polyethylene glycol liposome packets we used another genetically modified virus. Receiving the intramuscular injection with this virus genetically modified to express the Spike protein, the Spike protein will again be capped by our antigen presenting cells, T lymphocyte and B lymphocyte, it will create anti- Spike protein antibodies for these antibodies to serve as a barrier against the penetration of the virus in our body. This includes the vaccines Oxford AstraZeneca, Johnson & Johnson Janssen, and Sputnik with a similar technology.
Vaccines called proteins – proteins – This is Novavax, from a new American laboratory. What happens? The genetic sequences that produce the Spike protein are inserted into an epithelial cell culture system. These cells produce the Spike protein directly and then this recombinant S protein is transformed into a vaccine. We have similar technology and very positive experiences with the triple diphtheria, tetanus and pertussis vaccine. They are highly immunogenic vaccines that have been adapted for the coronavirus. These S protein recombinants are injected in the muscle and are now offered to the immune system of the vaccinated following the same immune route of previous - lymphocyte T, B lymphocyte antibodies anti - protein spike, which will serve as a barrier to the penetration of coronavirus.
Vaccines of inactive coronavirus – They cultivate the virus in a high-security laboratory; the coronavirus is inactivated in the laboratory and is transformed into a vaccine. This is the CoronaVac that we have here in Brazil. The CoronaVac vaccine at this point differs from others in that it is the whole virus. So there we're going to make anti spike protein, anti-N protein, anti-envelope protein, in other words, it is a vaccine that offers more viral antigens for our immune system to react. In that sense she is quite complete.
Efficacy - Now let's put from the point of view of efficiency and the question of exam interpretation. The viral vector RNA vaccines and genetically engineered protein vaccine is based on protein S. Thus, answering the question: "did the vaccine work? Am I protected?" The correct test is to ask the serology is antibody anti IgM and IgG anti-protein spike, which are neutralizing antibodies. It doesn't make sense for me to use the first kits that appeared last year for coronaviruses to find out if you got the vaccine.
Because those kits measure N-protein, they will measure other antibodies to other components of the virus. For example, they may even serve to measure the anti-cortical response of Coronavac, but not for these other vaccines. Therefore, if we have to choose a serological test to know if the vaccine has worked, and if we are protected, it has to be the serology of the anti-spike protein antibodies.
Vaccine response time - we also have the time to order this test. It's no use getting the vaccine today and ordering the exam tomorrow. The immune system ideally needs three to four weeks to mount the entire immune response. So it's a test that we're only going to order after three to four weeks of the last dose of vaccine, it's no use asking after the first dose either. You must give the booster dose and wait a month to be able to take the test.
Virus variants - Do current vaccines work against new coronavirus variants? The Brazil variant? The UK variant? And the South African Variant? Apparently, they are working, yes. Preliminary data suggests that there is a very high circulation of the virus in countries that adopt less effective health policies; in these places the virus circulates more freely et in a much larger number of infected people. Brazil is in this group.
So, when the virus circulates freely among people, it evolves genetically. It starts to change and get bolder. We have to think that the virus has no obligation to bow to our species, if it can, it will dominate our species. That's how nature works. Therefore, the virus is out there and it's genetically evolving. There will come a time when it has a mutation and the vaccines will not work. And I ask you, why do we get flu shots every year? Why? Because the influenza virus evolves very quickly. And the coronavirus will also evolve very quickly.
Vaccines updated annually - So what I see: next year, 2022, we will have the vaccine update. Recombinant technology will be able to update the vaccine: RNA, genetically modified adenovirus and recombinant protein vaccine. This is because we already know what the genetic variants of the virus are, we know that they affect the Spike protein in certain regions, so the mutations have already been identified. What will you do? You're going to update the vaccine, you're going to insert these mutant sequences there, so next year we'll have an update on the vaccine from Moderna, Pfizer, Sputnik, Oxford, Janssen. Now, from the original coronavirus there will not be enough to update, because it will be the basic one, the virus that was initially identified; unless the strains are cultured in high security labs so you can mix mutant viruses with an original virus. Which is much more complicated and much more time-consuming.
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