This week the White House held a summit on the future of Covid-19 vaccines that brought scientists and vaccine manufacturers together to discuss new vaccine technologies. Officials said new vaccines are an urgent priority as Covid-19 cases in the US and hospitalizations rise again, vaccination rates reach a plateau, Covid-19 funding is running low and the virus itself continues to mutate.
But in recent months, scientists have also learned that the immune cells that provide lasting protection — known as memory B cells and T cells — can keep the worst effects of the most recent versions of the virus at bay, even if they’ve been trained to fight older ones. strains of SARS-CoV-2. Vaccine researchers are expanding their focus from antibodies to these memory immune cells as the new discoveries open a path to universal coronavirus vaccines.
However, universal vaccines are still a long way off — possibly years — based on approaches never used before. “That’s a scientific challenge,” Anthony Fauci, chief medical adviser to the president, said at the summit.
The good news is that far fewer people are dying from the disease compared to last winter’s spate of cases, spurred by the ommicron variant of SARS-CoV-2, the virus that causes Covid-19. The first round of Covid-19 vaccines still keeps the death rate at about 360 a day, according to the Center for Disease Control and Prevention. Still, health officials want to do better.
“While the vaccines are great, hundreds of Americans, thousands of people around the world are still dying every day,” Ashish Jha, the White House’s Covid-19 response coordinator, said Tuesday. “Building a new generation of vaccines will make a huge difference in ending this pandemic.”
The National Institutes of Health is already funding several research teams developing Covid-19 vaccines that protect against many different versions of the virus, protect against future changes in the virus before they occur, and protect against other coronaviruses.
From there, health officials are striving not only to develop vaccines that provide more sustainable protection against a wider range of threats, but also to rethink vaccination strategy in general. With a better understanding of long-term immunity, more robust vaccines and a comprehensive public health approach, health officials say they have a better chance of restoring normalcy.
B cells and T cells are the key to long-lasting immunity
Much of the discussion about vaccines and immunity to Covid-19 revolves around antibodies, proteins produced by the immune system that attach to the virus. And indeed, they are important.
Antibodies that primarily prevent the virus from causing infection are called neutralizing antibodies. A high concentration of antibodies in the body that block SARS-CoV-2 is an important indicator of good protection against reinfection. Antibodies can also serve as a way to mark invaders so that other cells of the immune system can destroy them.
But making large amounts of antibodies is very demanding on the body, so after an infection or vaccination, their production decreases over time. Another concern is that antibodies are very specific about where they attach to the virus. If the virus has a mutation at that attachment site — called an epitope — antibodies have a harder time recognizing the pathogen. That’s why some antibody-based treatments for Covid-19 are a lot less effective at stopping the ommicron subvariants.
Fortunately, the immune system has other tools in its chest. The bone marrow contains stem cells that differentiate to become B cells and T cells. Together they form the core of the adaptive immune system, which creates a tailored response to threats. After a virus invades a cell, it hijacks its machines to make copies of itself. White blood cells known as cytotoxic T cells, also known as killer T cells, can identify the wayward cell and cause it to self-destruct. This mechanism does not prevent infections, but it does prevent them from getting out of hand.
Another type of T cell, called a helper T cell, acts as an “on” switch for B cells, the cells that produce antibodies. After an infection dies out, some T cells and B cells turn into memory cells that linger in parts of the body, ready to recover if a virus resurfaces.
What do we now know about the adaptive immune response to Covid-19?
So far, the adaptive immune system seems to be holding up reasonably well. The first round of Covid-19 vaccines targeted the earliest versions of the virus, so many vaccinated people have had breakthrough infections, especially from the newer variants. But only a small proportion of those immunized have become seriously ill or have died.
That probably means that their immune systems couldn’t completely keep the virus out, but their immune cells could scavenge once an infection took root.
“A person’s neutralizing antibodies may not be up to the task, but if they have the T-cell response, that can make all the difference in severe disease,” said Stephen Jamesona professor of microbiology and immunology at the University of Minnesota.
Over the past year, many studies have confirmed the importance of memory B cells and T cells for long-term immunity against Covid-19 and answered critical questions about whether they can respond to new variants.
Researchers have discovered that lower levels of memory B cells were associated with a greater risk of breakthrough infections of the delta variant. On the other hand, B cells induced by Covid-19 vaccines could reactivate to make antibodies months after the initial vaccine doses.
Similarly, scientists found that vaccine-generated T cells were able to recognize SARS-CoV-2 variants such as omicron months later. “These data provide grounds for optimism, as most vaccine-induced T-cell responses remain able to recognize all known SARS-CoV-2 variants,” scientists wrote in a March paper in the journal. Cell.
Another study showed that Covid-19 vaccines generated strong T-cell memory that protected against the virus even without neutralizing antibodies. “I think the immunological memory elicited by vaccines is quite good and even maintained,” said Marulasiddappa Suresha professor of immunology at the University of Wisconsin-Madison who co-authored the study, published in the Proceedings of the National Academy of Sciences in May.
Whether this protection will hold up over the years remains to be seen. Experiences with previous coronaviruses such as MERS have shown that antibodies against the virus can persist for four years. However, Covid-19 is spreading at much higher levels and mutating more than MERS did during the initial outbreak. Future protection against the disease depends on the immune system and how much the virus itself will change, and scientists are keeping a close eye on both.
How scientists approach universal Covid-19 vaccines
Most vaccines to date are designed to fight one or a handful of versions of a particular virus. They present the immune system with a target that will allow it to prepare its defenses if the actual virus ever invades.
In the case of Covid-19, most vaccines coach the immune system to target the SARS-CoV-2 virus’s spike protein, which it uses to start the infection process. This helps the immune system to generate strong neutralizing antibodies. But the spike protein is one of the fastest mutating parts of the virus, making it a moving target.
The fact that B cells and T cells have managed to stop newer variants suggests that it is possible to tackle the virus in other ways. Instead of just making neutralizing antibodies that attach to the spike, the adaptive immune system could also produce non-neutralizing antibodies that bind to other parts of the virus that mutate very little or not at all. While these antibodies may not prevent an infection from taking root, they may be able to provide more durable protection against serious diseases that will be resistant to future SARS-CoV-2 variants.
Another approach is to present the immune system with a variety of different possible mutations of a virus, allowing white blood cells to prepare a response to a spectrum of threats and fill in the blanks.
Universal vaccines haven’t been deployed before, so researchers are in uncharted territory and the shots likely won’t be ready for a potential fall spike in Covid-19 cases. But the development of such a vaccine could ultimately reduce the need for boosters and give health officials a head start in countering future outbreaks.
In the meantime, US health officials plan to distribute: Vaccines reformulated to target newer Covid-19 variants by September, but it is not yet clear what the optimal strategy will be to deploy them, given the wide range of immune protection among the population. Between infections and vaccinations, the majority of people in the country have had some exposure to the virus, providing some measure of protection. And since the adaptive immune response to Covid-19 appears to be robust in most people, getting an extra shot may not be necessary for everyone.
One option is to seek out those with weaker immune systems for boosters. Researchers now have a rapid test to measure T-cell responses to Covid-19 that can identify people who are more vulnerable to reinfections or breakthrough infections.
While vaccines deal with the worst effects of Covid-19, infections are still proving disruptive. Covid-19 outbreaks are contributing to staff shortages in hospitals, schools and airlines, leading to delays and cancellations. And the more the virus spreads, the more opportunities it has to mutate in dangerous ways. Stopping this threat requires limiting infections, which in turn still requires measures such as social distancing and wearing face masks.
So as good as the next generation of vaccines may prove to be, they are only one part of a comprehensive public health strategy to contain disease.
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