The anti-Covid VACCINE produced by Johnson & Johnson, despite having been developed in the record time of a year like the vaccines of Pfizer, Moderna and AstraZeneca, actually comes from further afield: And H. Barouch, Professor of immunology at Harvard Medical School and director of the center for virology and vaccine research at Beth Israel Deaconess Medical Center, he began working on the characteristic mechanism of the vaccine, which is the use of an adenovirus to bring the antigen into our cells, since 2003, in the search for a vaccine against HIV. Barouch at 3.45 pm today will participate in the online event ‘Covid-19: developing a vaccine during a pandemic’, organized by the Department of Biomedical Sciences (Dsb) and the Institute of Biomedical Technologies (Itb) of the CNR, together with the University of Pisa.
Professor Barouch, how did your Sars-Cov-2 vaccine come about?
“We thought of using, as a vector for the vaccine, a modified and rendered harmless adenovirus, which can enter human cells but cannot replicate in them or damage the organism, already in the period 2003-2005, when we developed the Ad26 vaccine vector. , where “Ad” stands for adenovirus. In 2007 we published the first study about it. And in our HIV vaccine program, which continues and has taken a long time because HIV is a very insidious and ever-changing virus , we chose Ad26 for first animal and then clinical testing. Today we have reached phase 3 of HIV vaccine testing. The next step in using Ad26 was 2016, when we first applied Ad26 to a pandemic, that of the Zika virus. And then we were stunned … “
What amazed you?
“While the HIV vaccine still had a number of scientific challenges to solve, when we applied the Ad26 vaccine platform to Zika, we saw that, in both monkeys and humans, a single dose of the vaccine was sufficient to produce antibodies protective neutralizers in all monkeys and in the vast majority of human subjects. Experience with Zika showed us how powerful and efficient it could be for a more ‘docile’ virus than HIV. And with the Zika program we had the concept that that vaccine was so effective with just one dose. Then Johnson & Johnson (who acquired Crucell, the small Dutch biotech that worked with us at Beth Israel Deaconess Medical Center ten years ago) went on to develop Ad26 for other pathogens. In particular for Ebola: The J&J Ebola vaccine was developed for use in Central Africa, and was approved in 2020 by the European authorities “.
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Ebola was the first Ad26-based vaccine to receive approval …
“Through the Ebola program, J&J has shown that it can produce millions of doses of the vaccine. And formulas were developed that could be distributed in Central Africa, and didn’t require storage at sub-zero degrees. That’s when J&J developed the formulas that allow the vaccine to be stable, in liquid form, at refrigerator temperatures. Formulas that we now also use for the Covid vaccine. All this set of experiences with Ad26 for HIV, Zika and Ebola was invaluable in January 2020 when the pandemic alarm went off, and we understood the need for a vaccine to counter Sars-CoV-2. And we thought that a single dose vaccine that didn’t require sub-zero temperatures, and could stimulate the production of antibodies in all individuals, was something that could be useful against Covid-19. “
What allows your vaccine to do without sub-zero temperatures?
“Inside the adenovirus Ad26, we insert the instructions that human cells need to produce the antigen, or the spike protein of Sars-Cov-2, in the form of DNA. This difference with vaccines that instead use a molecule of RNA is what counts for the storage temperature: DNA is a much more stable molecule than RNA, and therefore does not need sub-zero temperatures to preserve itself “.
Today we are all concerned about the variants of Sars-CoV-2. How much do they reduce the effectiveness of your vaccine?
“From the point of view of efficacy, the most important results of my vaccine are 100% protection against hospitalization and death, and 85% protection against the severe form of the disease. The efficacy against the form moderate of Covid is instead lower: 72% in the United States, 68% in Brazil and 64% in South Africa: here, this is also the answer to your question about the Brazilian and South African variants. In particular, it is interesting to note that the most feared variant , South Africa’s B.1.351 reduces the effectiveness by only 8 percentage points. The most important thing, in my opinion, is that the effectiveness against severe forms of the disease is not reduced at all, even with variants: in the USA it is 86%, in Brazil it is 88% and in South Africa it is 82%. It can be said that at this moment our vaccine is, among those approved, the one that seems most effective with the variants, including the variants that are able to partially escape from neutralizing antibodies “.
How long does your vaccine protection last?
“We can’t know yet: we’ll have to wait and see. But what we do know is that a single injection of the Zika Ad26 vaccine increased the antibody titers in almost all subjects, and the antibodies lasted for more than a year. “
What makes the J&J vaccine effective with just one dose?
“As I said before, the adenovirus Ad26 is a vector. But in reality it is not just a vector, because its envelope – being a virus anyway – helps to trigger the immune system’s response. We can consider Ad26 as a sort of adjuvant natural ‘for the immune response, and not just as a mere’ delivery vehicle ‘for the vaccine “.
How will you deal with the variants?
“Like all other vaccine manufacturers do, together with J&J we are developing updated versions of the vaccine that include South Africa variant B.1.351, and those will be evaluated in animals and humans. What we don’t know, though, is whether it will be. necessary, because the current vaccine already shows a high level of efficacy against the variant “.
When did you decide to face the Covid challenge?
“I will remember the evening of January 10, 2020 for the rest of my life. It was the day of the annual Barouch Lab retreat: once a year I bring together all the people in my group and we hold a seminar talking about everything we have done in the last year, and plans for the future. On January 10 of last year, talking about the articles in the newspapers, we commented on the fact of the forty-one cases of a mysterious pneumonia. That had caused a death. We found it already alarming, for the case description. I was concerned mainly because it was clear that it was a new respiratory virus: therefore there was no pre-existing immunity in the human population, and there was a suspicion that it could be transmitted from person to person. I found it alarming that the clinical disease appeared to be less severe than previous SARS and MERS outbreaks … “
Why did she find it more troubling that the new disease was less severe than SARS and MERS?
“Mind you: if one is hit by Covid, the fact that it is less serious than Sars is obviously a good thing. But the problem is that I had already guessed, at that point, that if the disease is less serious, the chances of having carriers increase Asymptomatic. For SARS and MERS, everyone who was infected got so sick that they developed a high fever and the critical thing is that they developed a fever very early. So as long as you can control people for fever and respiratory symptoms, it was possible to isolate them and quarantine them very easily. While with that “mysterious pneumonia” (which we now know is Covid-19) people could be infected asymptomatically and spread the virus very much. this, of course, turned out to be correct. A virus that causes asymptomatic or pre-symptomatic infection in individuals who may still be contagious makes it much more difficult to control a pandemic through against traditional public health measures such as solitary confinement and quarantine. And this is why we thought on January 10 last year that we should immediately start working on a vaccine. “
So did you get busy right away?
“We started working on it on the evening of January 10, 2020. After we all got home from our retreat, I emailed four scientists in my group and said, “let’s analyze the sequence.” Which was made public that very day by Chinese researchers. Starting that same night, we began analyzing the sequence, compared it with SARS and MERS, and identified the spike gene as a target for a vaccine. During that weekend, we developed sequences for the vaccine candidates, and upon returning to the lab on Monday, January 13, we began the process of creating synthetic genes and prototyping a vaccine. Two weeks later, on the weekend of January 25th, as the outbreak in China exploded and infected thousands of people, I called Johan Van Hoof, who was the head of vaccines at J&J. And I said to him, “Johan, are you doing something about this? It looks like we really need a vaccine here.” The following Monday morning we brought our teams together and decided just then that we would partner with the J&J collaboration that had worked so well for HIV and Zika. The time had come to use Ad26 against Covid “.
What is your prediction on the future of the pandemic?
“The most important thing now is to quickly distribute all vaccines, not just ours, but all vaccines that are safe and effective. They need to be distributed to the world, to global populations as quickly as possible, not only to protect the health of individuals and to create herd immunity for populations, but also because the faster we can keep the current pandemic under control, the less they will be. the possibilities of emergence of new viral variants. Which in the future could become even more problematic than the variants we have today “.