The Covid-19 pandemic was a long battle between a generational virus and scientists working at a breakneck pace to fight it. Following the development of the remarkably effective first-generation Covid-19 vaccines, the virus has given its answer: more infectious variants have emerged that can infect people who have been vaccinated or previously infected. This is by no means a failure of vaccines, which continue to protect millions of people from the most devastating effects of the virus. But science must be ready to make its next move.
Initially, people who received mRNA vaccines from Pfizer or Moderna were about 95 percent less likely to receive Covid-19 than those who did not have previous immunity. Protection against serious illness was strong. Countries with high vaccine use have seen a sharp drop in coronavirus cases, hospitalizations and deaths.
Given these powerful tools, it seemed that the worst of the pandemic would soon be behind us. And it probably was. Despite the astonishingly large part of the country that became infected during the Omicron wave this winter, Covid-19 deaths were lower or not far higher than those of previous waves that cause far fewer infections. These deaths are much less likely to occur in those who have been vaccinated than in those who have not. In addition to vaccines, antiviral drugs have been developed that are particularly useful for those who have not been vaccinated or immunocompromised. There are now many tools that make Covid-19 less of a threat than it was in 2020.
It is also true that the road out of the pandemic was more uneven than many had hoped. More than half of the US population is infected, and some more than once. Importantly, post-vaccination and re-infections rarely bring people to the hospital, but the experience can be miserable and devastating.
The situation with Covid, in terms of hospitalizations and deaths, is much better now, but that is not the best thing science can do, and we must continue to move forward against it. There are several ways to improve the state of immunity.
Questions about the ongoing Covid-19 pandemic, as well as vaccines and treatments.
My research team is studying the maintenance of immunity and we have learned that details matter. To repair dents in the immune armor, scientists need to understand what is still working, what has slipped and why.
After vaccination or recovery from infection, the immune system leaves several protective layers to counteract any future exposure to viruses. One component of lasting immunity is made up of memory cells that patrol the body looking for any signs of the virus. If such evidence is found, memory T cells can kill infected cells, while memory B cells rapidly produce antibodies that are proteins that can adhere to viruses and prevent them from infecting more cells.
Memory cells had enough time to find and turn off the virus before the coronavirus infection caused noticeable symptoms. But as fast-replicating variants such as Delta and Omicron have emerged, the period of time before a person develops symptoms has shrunk, making it difficult to clear the infection before feeling sick. Memory cells usually catch up with the virus before it spreads through the lungs and causes severe illness, but in the meantime a person can feel quite awful.
Covid vaccines do a good job of inducing all types of memory cells. These cells remain stable over time and are relatively impermeable to mutations in variants such as Omicron. This is good news and helps explain why available vaccines continue to drastically reduce severe disease, even from variants that have changed significantly from the original coronavirus strain. However, it is clear that in order to prevent human disease, scientists need to find ways to further shorten the response time of these cells.
The second layer of immunity consists of specialized soldiers of the immune system called plasma cells. Each plasma cell produces antibodies to an astronomical clip – several thousand every second, whether the virus is around or not. Because the antibodies themselves remain for only a few weeks, the persistence of plasma cells is the key to replenishing and maintaining protective antibodies over time.
Covid vaccines behave very differently from each other in terms of how many plasma cells are made and how long they live. This can be assessed by measuring the levels of antibodies in the blood over time. Both Moderna and Pfizer mRNA vaccines lead to very high initial levels of protective antibodies. These antibodies then drop sharply for six to nine months before stabilizing between 10 and 20 percent of their peak levels. Because peak levels of plasma cells and antibodies after mRNA vaccination are so high, even a 90% loss would probably still leave a person strongly protected against symptomatic infection if the virus did not evolve into new variants.
In contrast, the Johnson & Johnson single-dose vaccine induced far fewer plasma cells and antibodies initially, and its effectiveness against Covid-19 was lower than that of mRNA vaccines. The Food and Drug Administration has understandably limited its use due to the risk of a rare but serious side effect of blood clotting. However, the Johnson & Johnson vaccine maintains and may even slowly increase protective antibodies over time. Ideally, people would receive high levels of protection against mRNA vaccination and then maintain it, as seen with a single-dose vaccine such as Johnson & Johnson’s.
So, given this state of affairs, what are the workable things that can be done to improve the duration of immunity? There are several options, ranging from options available now to what I expect to come in the next few years.
First, there are boosters. Because antibodies are maintained at high levels when the Johnson & Johnson vaccine is given as a booster after mRNA vaccines, it is worth considering whether there are ways to safely resurrect this booster vaccine, perhaps by better defining groups. at risk for rare blood. side effect of clotting.
Second, the vaccines and boosters we have currently targeting a strain that has been missing for more than a year will be updated to match variants like Omicron. Matching vaccines to the virus is likely to help antibodies work better, potentially providing them with less buffer space to reduce them. Getting a booster with an Omicron-specific vaccine can help prevent people from becoming infected or getting the virus back.
While frequent boosters could restore some of the levels of protection of the original vaccines against the virus, given the lower absorption of boosters so far, scientists and stakeholders must also look for longer-term solutions and new tools to stop infections.
Vaccines given by the nose or mouth, memory cells and antibodies near the site of infection and offer potential ways to prevent symptoms and perhaps even infections in general. Some of these vaccines are now in clinical trials and may become available soon.
Groups of researchers are also studying single vaccines that could work against all versions of the new coronavirus. These vaccines, which are designed to be resistant to variants, make it difficult for the virus to overwhelm the immune system. They showed great promise in animal experiments. Some of them are entering clinical trials and may be available over the next few years.
These types of vaccines can buy us long-term protection against infections and diseases. When we combine together, our anti-Covid-19 weapons are growing. This is not the end of the chess match. Our next moves are coming soon.