The Pfizer vaccine should give hope to Israel and the world - here’s why

 
Pfizer
(photo credit: AP)

While Israeli officials claimed to be in advanced negotiations with the company, sources say it is unlikely that the Jewish state will top Pfizer’s distribution list.

The biopharmaceutical giant Pfizer Inc. on Monday announced its vaccine candidate was found to be at least 90% effective, according to an interim analysis of the company’s global Phase III study.
While Israeli officials claimed to be in advanced negotiations with the company, sources say it is unlikely that the Jewish state will top Pfizer’s distribution list. Nonetheless, news of Pfizer’s success could be meaningful for Israel.
This is because the Pfizer vaccine, known as BNT162b2, is based on BioNTech’s proprietary mRNA technology. According to the company’s website, it encodes a portion of an optimized SARS-CoV-2 spike glycoprotein, which is considered the main target of virus neutralizing antibodies.
The Moderna Inc. vaccine candidate, which is in the midst of its own Phase III trial and that Israel has pre-purchased, is also an mRNA vaccine. According to Cyrille Cohen, head of the immunotherapy laboratory at Bar-Ilan University, if Pfizer’s vaccine works, it is likely that Moderna’s will also show good results.
The Jerusalem Post asked Cohen, who is also a member of the advisory committee for clinical trials on coronavirus vaccines at the Health Ministry, to explain the Pfizer and mRNA vaccine candidates and their implications on the COVID-19 crisis specifically and the medical world in general.
How do the Moderna and Pfizer vaccines work?
The Pfizer and the Moderna vaccines take nanoparticles – “small beads filled with mRNA” – and inject them in the body, Cohen said. Cells eat those particles and “learn” how to make a viral protein. Once they make the protein, the body sees it as a foreign antigen and creates antibodies against it.
“The body’s antibodies and T-cells patrol around until they meet the real virus and then they will stop it from attacking our body,” Cohen said.
So, what is different about these vaccine candidates?
Cohen said that most of the vaccines being developed today against the coronavirus are targeting a protein called the spike protein.
“Coronavirus has spikes made of protein, which are considered the best targets for our immune system to attack to prevent the binding of the virus to our cells,” he said.
That spike is divided into several parts and the most important part of it is the “receptor binding domain,” known as the RBD, which is the part actually facilitating the attachment of the virus to people’s cells.
Moderna is injecting the mRNA that codes the whole spike. Pfizer is injecting the mRNA code only for the RBD part of the spike.
“Moderna is injecting the mRNA that codes for one whole protein,” Cohen clarified. “Pfizer is injecting mRNA that produces three domains of this smaller part... The strategy is similar.”
Let’s take a step back. What is mRNA?
MRNA is the transient or limited part of the genetic information in an organism.
“The basic dogma of molecular biology is that we have DNA in our genes – like having cookbooks in a library; the library is our cells’ nucleus. It is forbidden to take the cookbooks out of the library,” Cohen said. “It is forbidden because we are afraid that if we do that, something will happen to the books.”
Instead, scientists can enter the library, where there is a copy machine, and copy one page of a cookbook and then take that page out of the library and to the kitchen.
“That page is mRNA – basically the recipe for a protein,” Cohen continued. “The proteins are cooked – or produced – in our cells, in a ‘kitchen’ we call cytoplasm.”
He said that just as scientists are “nervous” to take a book from inside the library outside, it is also complicated to take a book from outside the library and try to bring it in. But taking a synthesized one-pager and introducing it into a cell is much easier technically to do.
So, mRNA in the case of vaccines?
“Vaccines are trying to expose our body to foreign substances like viruses so our body will study them and develop immune responses against them,” Cohen said. “So, here, the idea is that you are taking one protein or the information of one protein of the virus and giving it to the body – the recipe for one protein in the form of mRNA.
“When our cells get the recipe, they read it and actually produce viral proteins without producing the virus,” he continued.
On the one hand, there is no chance of infecting the body. On the other, the body is exposed to the virus and it can use those spikes to learn how to recognize the virus and create an antiviral response against it.
This is exciting now, but could the Pfizer success have long-term application, too?
According to Cohen, one application would be in the use of “cancer vaccines.”
“There is much in common between virus and cancer from an immunological standpoint,” Cohen said. “One option to help the immune system to fight cancer is to ‘reprogram’ it to recognize cancer associated proteins – targets that can discriminate between healthy and tumor cells. Thus, you could give your body the genetic information coding for these ‘cancer proteins’ to stimulate the immune system to attack the cancer cells.”
Another idea would be to replace mutated proteins, such as in the case of ischemia, when people have an insufficient blood supply due to lack of vessels.
“In a disease like ischemia, you need to generate blood vessels and to do that we have protein in our body that is able to tell it we need more blood vessels right now. Sometimes, we don’t produce enough of that protein,” Cohen explained. “With mRNA technology, you could inject the recipe for the protein into the body and quite quickly your cells would produce that factor and would promote the creation of new blood vessels.”
He added that the capacity for producing mRNA vaccines could be applied for other viruses, such as the flu or Zika virus.
And you trust Pfizer?
“Pfizer is a very serious company and they would not mess around or say things that are not real,” Cohen said. “Could it end up 80% effective or even 95% – yes. But I do not think it is going to be 20%.”
He described Monday’s announcement as a “huge leap for vaccine research” and said that it gives the world hope that the vaccine strategy against the novel coronavirus could work.
“It took 63 days from the moment Moderna had the genome of the virus until people were enrolled in a Phase I clinical trial – that is laudable.”
Is there a ‘but’?
“The ‘but’ is that we have to be moderate in our enthusiasm,” Cohen said.
For starters, despite all the research, there is still no published data on the efficacy of the vaccine in the elderly population, over the age of 65.
Second, since we still do not know if the coronavirus is going to mutate and/or if antibodies or T-cells are long-lasting, it is unclear to what extent Pfizer’s vaccine – or any other vaccine – would provide long-term protection.
He also cited a potential logistics challenge that could hold up the distribution of the vaccine: mRNA is very fragile and the vaccine doses would need to be stored in negative 70 degrees Celsius.
“Right now, Pfizer is working on building sites where it can keep the stock of the vaccine and how it can manage to distribute around the world,” he said.
Another researcher, Rivka Abulafia-Lapid, a senior virology lecturer at the Hebrew University of Jerusalem, said there is also concern about the long-term effects of mRNA vaccines on the body.
“We are looking at short-term safety issues – headache, fever, vomiting – but we cannot see what happens in the future – what we will see on the cellular level in a couple of years,” she said. “This is not something easy to predict.”

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