By Brenda Goodman, Jacqueline Howard and Michael Nedelman, CNN
(CNN) — As waves of new coronavirus variants circulate around the world, one thing is clear: Human immunity to the virus fades over time.
For lasting coverage against the virus that causes COVID-19, scientists are working 24 hours a day to expand next-generation vaccines. But some of the nuances about why and how immunity to covid-19 fades remain a mystery.
The greatest drops in immunity, which occur around 4 to 5 months after vaccination and up to 8 months after infection, but can vary, oppose the symptoms, infection, and illness of Covid-19. Protection against serious consequences, hospitalization and death remains much greater. for a longer period of time, but even this degrades to some extent, especially for the elderly and those with compromised immune function.
Since the early days of the pandemic, scientists have known that the coronavirus has a design called spike protein and that it uses this crown of spikes to penetrate the cells it attacks. Our COVID-19 vaccines create antibodies opposite those complex proteins that bind to the virus’ coupling sites, preventing them from infecting our cells.
However, our protection against the virus is being reduced, in part because the virus moves like a fugitive in disguise, capturing mutations that change the shape of its spikes in tactics that make it less recognizable through our immune system.
But there is one piece of the immunity puzzle that scientists are urgently seeking to solve, and that is whether the component of this drop in our coverage may be the result of the generation of mRNA used to build some COVID-19 vaccines, such as those developed by Moderna. and Pfizer/BioNTech, which were the first in the world to use this platform.
“Some vaccine platforms offer a very high degree of coverage, but the durability is very long,” Dr. Anthony Fauci, director of the National Institutes of Allergy and Infectious Diseases, said in an interview with CNN.
Fauci said the mRNA platform may be just one component of it.
In clinical trials, new mRNA vaccines have been shown to be strangely effective in protecting other people from illness, hospitalization and death, at least in the short term. Fauci said mRNA vaccines have other benefits as well. new variants, for example.
“We have a very smart platform with mRNA,” Fauci said. But let’s try to be better. Because our experience is exclusive to the coronavirus, but I doubt it, is that the sustainability of the reaction in which you can be better. “
To be fair, Fauci said we might not know how long the immunity induced through those types of vaccines can last until mRNA is used to make vaccines opposed to some other type of pathogen, perhaps one that doesn’t replace as much as SARS-CoV. -2, the virus that causes Covid-19.
Definitive can take years.
In the meantime, he says, we can’t wait. We want vaccines if we want to keep Covid-19 at bay.
“We have very smart vaccines, but we want to get better platforms and immunogens, with adjuvants that allow us to have a greater durability of protection,” Fauci said. Adjuvants are additional ingredients in vaccines that help them function better.
Other experts agree.
Deepta Bhattacharya runs a lab at the University of Arizona where she studies the lifespan of plasma mobiles, a type of long-lasting mobile that produces protective antibodies. He is also interested in how vaccine technologies influence the patience of those mobiles in our bodies.
What we can say after more than a year of delight with mRNA vaccines is that their coverage starts well but ends up disappearing faster than the immunity left after a covid-19 infection, according to Bhattacharya.
“There have been some parallel studies that have mRNA vaccines for infection-induced immunity, and it turns out it’s sliding a little faster than that,” Bhattacharya said.
Although he cautioned that coverage after an infection varies greatly from user to user simply because everyone’s immune formula is a little different. At the moment, there’s no smart way to know how well a specific user’s immune formula is reacting to a vaccine, which is why it’s vital to be vaccinated, even if you’ve already had Covid-19.
He added that by comparing the functionality of mRNA vaccines with adenoviral vector vaccines, such as those developed through AstraZeneca and Johnson.
With adenoviral vector vaccines, antibody levels don’t seem to rise as much as they do with mRNA vaccines, but they seem to persist for longer periods at those lower levels, indicating some difference in the body’s reaction that we don’t understand. .
In a giant study of more than 35,000 healthcare workers in the UK, for those who were not vaccinated, those who had received two doses of the Pfizer/BioNTech mRNA vaccine were about 85% less likely to get a COVID-19 infection. , thanks to about two and a half months after your current dose. But within six and a half months, that coverage against infection had dropped to about 51 percent.
The study’s follow-up period was extended from December 7, 2020, when vaccines were first given to healthcare personnel in the UK, to September 21, 2021, so it comes with Omicron infections.
Healthcare personnel with two doses of Astrazeneca’s adenoviral vector vaccine were approximately 58% less likely to contract Covid-19 infection compared to those who were not vaccinated, for about two and a half months after vaccination, but the effectiveness of this vaccine gave the impression of accumulating over time, reducing the risk of infection by more than 70% approximately seven months after a momentary dose.
Healthcare personnel who contracted a Covid-19 infection, most of them in March 2020, before the vaccine era, were 86% less likely to be reinfected, and this coverage lasted up to a year. After a year, it fell to about 69 percent in unvaccinated staff, which was even higher than mRNA-protective vaccines alone.
Workers who had stuck to Covid-1nine and then got vaccinated had the most productive coverage of all, a more than 90% decrease in the threat of re-contracting Covid-1nine, and this combined coverage remained at the top for the duration of the study, which was more than nine months.
This evidence and other studies, Bhattachayra said, that our immunity to Covid can be altered to make it last longer.
“I think it’s right to ask for more of our vaccines and they have that coverage longer,” Bhattachayra said.
“I think obviously there’s still room for improvement because there are some vaccines that work better” in terms of sustainability, he said. “There is no doubt about it. “
Starting at two months of age, doctors propose that young children be vaccinated against Haemophilus influenzae, or Hib, a common bacterium that can cause serious infections if it invades the lungs, blood or brain. These bacteria are covered with chains of sugars, or polysaccharides, that mask them from our immune system.
In the 1980s, scientists discovered that it was conceivable to use those sugar chains to make a vaccine to protect children from serious infections.
“The initial Hib vaccine was a polysaccharide vaccine, but it didn’t induce long-lasting antibody levels, so we don’t even use it now,” said Dr. Gregory Poland, an infectious disease expert who studies how the immune formula responds to vaccines at the Mayo Clinic in Minnesota.
Today’s Hib vaccine still contains sugar chains, but they are attached to pieces of protein that stimulate some other component of the immune formula to boost bacteria. This is called a protein conjugate vaccine.
Another example of a vaccine that ultimately did not provide lasting immunity was the pneumococcal pneumonia vaccine. It also began life as a polysaccharide vaccine, but was replaced by a conjugate protein after researchers thought this update could increase its effectiveness. Protection.
Some vaccines use additional ingredients, called adjuvants, to overstimulate the immune formula, increasing the strength of the coverage other people get. These types of vaccines are used for the elderly and others whose immune formula needs an extra kick, so to speak, to work.
Some vaccines do this inherently, just because of the way they’re designed, Fauci said, and the nanoparticles built into some experimental vaccines are one example.
Fauci added that he didn’t know why the immune reaction triggered by mRNA vaccines might not last any longer. However, he has some theories.
One of the first mistakes in the progression of mRNA generation was that when chains of molecules called nucleic acids were injected into animals, they triggered an immune reaction too quickly. commands, before cells can simply read them and build the proteins they were encoding.
A breakthrough in turning those commands into vaccines that the scientists who developed them figured out how to chemically modify mRNA to hide it from the immune formula until it can get internal cells, reducing the threat of getting sick.
“They changed the molecule to remove the inflammatory part of it, to allow it to be used as a vaccine, that may be, and I pointed it out 15 times, it may be the explanation for why,” Fauci said.
“Maybe if we use this mRNA, but add another adjuvant to it, you can get a very intelligent response, the more productive of both worlds, you can get the genuine advantages of an mRNA with a little more durability, if you load it, it’s an adjuvant of the molecule itself that is inherently adjuvant. “
Bhattachyra has a theory as to why the mRNA platform would possibly not last that long.
He said those vaccines instruct cells to build complex proteins from the virus and then place them on their surfaces, where they can be detected through the immune system.
But cells are giant compared to viruses — about a hundred times larger, he said , and viruses contain about 25 trimers of spike protein on their smallest surface, making them dense. A trimer is a type of chemical compound or molecule composed of 3 elements.
“I don’t know what the density of peak proteins is in a cell; it may not be as high as in a virus, for example,” Bhattachyra said. No one knows what the cells that express the spikes look like and how they look a lot like the virus they target.
“Possibly, spacing is rare and you just don’t get the trigger point you want,” he said, adding that “it’s natural speculation. “
EE. UU. se is now at a point in the pandemic where fitness officials are grappling with the fact that for immunity to covid-19 in the community, the country will want to administer normal base boosters, or in all likelihood annual, or want to launch an entirely new vaccine.
All vaccines have strengths and weaknesses; however, some of the country’s leading vaccine experts say there are more studies on the sustainability of COVID-19 vaccines that are lately being used as a potential weakness, as vaccine-induced immunity may decline in 4 to 6 months.
For example, the recent wave of Omicron in the United States, coverage presented through vaccine boosters increased more than 4 months after more than 90% to about 66% for coverage versus Covid-19 emergency room visits and 78% versus hospitalizations. Dr. Peter Hotez, CNN’s medical analyst and virologist and co-director of the Center for Vaccine Development at Texas Children’s Hospital, told CNN.
“The big unknown is: how much of this drop is due to something due to the Omicron variant?Or is it a weakness of the generation and does it not hold up?And it’s very difficult to solve,” Hotez said. All vaccines have strengths and weaknesses, and it may not be that for mRNA it does not produce lasting protection. Possibly I would use mRNA vaccines to temporarily immunize a population, stabilize it, but over time, it will have to reach a heterologous spice that is another generation. “
Hotez, whose lab has developed a COVID-19 vaccine called Corbevax, said the White House convened vaccine experts at a special assembly to “determine” whether the generation has this weakness and what that means for long-term strategies.
In an effort to find the answer to maintain sustainable coverage against Covid-19, several study teams are running to expand so-called “next generation” vaccines that aim to induce more sustainable coverage and even “pan-coronavirus” vaccines, which offer coverage against various variants of the coronavirus that causes Covid-19.
“How to make vaccine-induced Covid responses more sustainable?How to make this long-lasting mobile plasma induction procedure more efficient?That’s the call of the game now,” said Dr. Barton Haynes, director of the Duke Human Vaccine Institute. .
“There are a number of teams working with mRNA for next-generation vaccines, very aware that for those vaccines to last longer, breakthroughs need to be made,” he said.
Haynes is also running a type of vaccine: a nanoparticle containing fragments of the coronavirus’ spike protein. This vaccine also includes an element that improves the immune response, known as an adjuvant.
A key long-term goal is to create a more universal vaccine that can fight new variants of this coronavirus, as well as others that cause colds and even those that we have not yet identified. The protein-based vaccine is one of many that target sites were kept in the spike protein, the ones that don’t mutate, so that they don’t obstruct its ability to infect human cells.
And Haynes said studies with monkeys show it does a bigger job than mRNA vaccines in generating those types of antibodies that also offer broader coverage. This is possibly due to a combination of how the adjuvant works to boost the immune system. , and the design of the nanoparticle itself, which almost resembles a virus, he added.
Regardless of the vaccine platform, “we are all in favor of formulations that induce long-acting antibodies and other types of mobile T immunity. “
Until now, the coronavirus pandemic, vaccine coverage has been measured through the presence of antibodies in the blood. Antibodies are proteins produced by the immune formula to help fight infections. But the human immune formula is not limited to antibodies.
The immune formula reaches a large number of actors, adding B cells, which produce antibodies, and T cells, which target inflamed cells during an infection, and T cells are a component of emerging discussions about the sustainability of vaccines.
A one published in the journal Cell in January showed how other portions of the immune formula play a role in the durability of coverage after Covid-19 vaccination.
The study found that among 96 vaccinated adults, although antibody levels decreased compared to coronavirus variants, T cells were induced through COVID-19 vaccine types: modern vaccines, Pfizer/BioNTech, Johnson.
“The most important thing for our study was that we collected all those samples in one position with the same techniques and did all the experiments one by one, so it was a fair one-to-one test,” said Shane Crotty, a virologist and professor at the La Jolla Institute of Immunology, who was one of the authors of the study.
In addition, those vaccines have developed other technologies. Moderna and Pfizer/BioNTech are mRNA vaccines. Johnson
“The mRNA vaccines, Moderna and Pfizer, generated those 4 categories: antibodies, reminiscence B cells, helper T cells, and killer T cells. Overall, the mRNA vaccines generated the 4-way vaccine,” Crotty said, adding that among those vaccinated with Johnson
“So there were other mixes out there,” Crotty said. “Our immunological knowledge is consistent with knowledge of vaccine efficacy from clinical trials and real-world studies that, overall, mRNA vaccines are better than J’s.
Many experts seem to agree that discussions about long-term vaccination methods against covid-19 have the precise goal of vaccines: to prevent the spread of the coronavirus or to prevent other people from going to the hospital.
“So if your purpose is to prevent new infections in our society, then yes, we are going through to have to keep passing to pass, because our antibody levels pass to pass, no matter what kind of vaccine we get. Jen Gommerman, a professor and acting director of the Department of Immunology at the University of Toronto, told CNN.
He added that among vaccines for emergency use in the United States, the rate of decline of the Johnson vaccine.
“So the amount of uncooked antibodies in our serum is going down to a point where it’s vulnerable to infection and the only way to recover those antibodies temporarily is to become inflamed or reinforced,” Gommerman said.
“However, if we check effectiveness against hospitalization and serious illness, published data show that three doses of the mRNA vaccine verify adequate protection against hospitalization, ventilation and death,” he said. “For me personally, I would get a fourth dose if I knew it would work for public health reasons. But personally, I don’t think I want a fourth dose to protect me from serious illness, hospitalization, or death. “
There are many questions to answer about COVID-19 vaccines and immunology, John Wherry, director of the Institute of Immunology at the University of Pennsylvania’s Perelman School of Medicine, wrote in an email to CNN.
These questions include: How long do memory B cells and memory T cells last?How do vaccines containing the original coronavirus, known in Wuhan, China, induce an effective immune memory against all variants so far?What immune mechanisms provide cover against infection?Unlike coverage for serious illness, hospitalization and death?Why do other people react to these vaccines?
“These and many other questions still need answers if we are going to use this platform more effectively,” Wherry wrote. These questions also need answers in the context of vaccine sustainability, especially since the durability of coverage and the durability of immune responses themselves are similar. – but identical, according to Wherry.
For mRNA vaccines, “the durability of coverage is comparable to that of other types of vaccines based on analyses we have seen on adenoviral platforms rather than mRNA. Durability of immune responses: It has been difficult to make an accurate comparison in fact studies longitudinally during an era of time applicable to answer this question,” Wherry wrote in his email.
After all, vaccines have only been around for about a year and a half, and the exact answer to questions about sustainability may lie in the advent of boosters and the emergence of emerging infections.
“This last point is applicable because it particularly influences the duration of immune responses over time,” Wherry wrote of advanced infections. “The bottom line is that the information looks very promising for the duration of immune responses and protection against serious diseases. Protection against benign diseases is much more complicated for this virus and can only be achieved transiently when antibody levels are extremely high.
El-CNN-Wire ™
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