Here’s what experts say about the timing of flu and Covid vaccinations
OIn recent weeks, flu cases have begun to spread across the US, with spikes in the Southeast and South Central. Influenza hospitalizations are also on the rise. According to the Centers for Disease Control and Prevention’s flu surveillance team, all signs point to an earlier than usual flu season.
At the same time, hospitals across the country are filling up in children who have RSV – a virus that causes cold-like symptoms that can sometimes lead to serious illness, especially in infants and older adults.
With a third Covid winter approaching and public health precautions like masks and social distancing all but abandoned, the next few months could see the US healthcare system pushed to capacity by multiple increases in respiratory illnesses.
That’s why experts advise that the best thing people can do to protect themselves and prevent their local hospitals from being overwhelmed is to get immunized against circulating viruses. Pfizer’s experimental RSV vaccine is still in testingbut Covid-19 and flu vaccines are now available almost everyone.
Experts agree that the best time to vaccinate is now, before these viral waves grow into waves. But there are other, more subtle questions of timing that scientists are still investigating, including whether the time of day or combination of vaccines matters. Here’s what we know and what we don’t:
Does taking the flu and covid shots together make them less effective?
Probably not. The science is clear that the human immune system is sophisticated enough to handle seeing more than one antigen at a time and respond in a robust manner. And there is a lot of data to support this, including trials of combination vaccines such as the MMR (measles-mumps-rubella) and DTap (diphtheria, tetanus, pertussis) vaccines, which have been in use in the US for decades.
“The immune system is amazing at recognizing many things at the same time,” said Shane Crotty, an immunologist at the La Jolla Institute for Immunology. “In your gut alone, your immune system is fighting 500,000 potential targets. Adding one more thing to that is usually like a drop of rain falling into the ocean.”
Vaccines primarily work by activating two types of adaptive immune cells. The first are B cells, which produce antibodies that recognize bits of the bacteria or virus – in the case of SARS-CoV-2, its spike protein. Others are T cells, which roam the body and kill any infected cells, as well as coordinate the activity of other immune system players.
If a person’s body has already seen a particular virus, either in the form of a vaccine or previous infection, then a booster shot or annual flu shot serves to activate pre-existing populations of B cells that already contain instructions for use. creation of antibodies specific for those pathogens. In other words, vaccines usually do not compete for immune resources. The human body also keeps a reserve of B cells capable of making new antibodies against any new threat.
“In most cases, you can give the two vaccines together and everything works well,” Crotty said. However, some vaccine components that are intended to boost the immune response, called adjuvants, can interact or interfere with other injections when given in combination. mRNA Covid vaccines contain an adjuvant in the form lipid nanoparticles, the flu shot doesn’t work. Definitive evidence is not yet available on how administering the two injections together affects the effectiveness of any other injection.
That’s why Crotty advises people to get flu and Covid shots in different doses – arms for adults and older children, legs for toddlers. “The immune system certainly has no problem recognizing vaccines if they’re given that way because they’re two different processes going on simultaneously in localized ways,” he said.
Although there is not yet much data from human studies, laboratory experiments suggest that even combined injections do not reduce effectiveness. One study published last year showed that mice and ferrets vaccinated simultaneously against SARS-CoV-2 and H1N1 flu produced the same levels of antibodies as animals that received the vaccines in sequence. When later infected with these viruses, both vaccination strategies protected the animals from severe disease.
In fact, some researchers are already looking into whether the two vaccines could be combined into one injection. This summer scientists in China registered that their combination SARS-CoV-2/mRNA influenza vaccine protected mice against co-infection with H1N1 and the Alpha and Delta variants of SARS-CoV-2.
The only reason to space them out, experts say, is if you’re someone who tends to experience more intense reactions to immunizations, things like muscle or joint pain, chills and headaches. It is possible that these reactions may be worse if you receive both injections at the same time. A CDC study published in JAMA in July found that among 981,000 individuals, concurrent flu vaccination and a Covid-19 booster was associated with an 8% to 11% increase in such systemic side effects, compared with the Covid-19 drug alone.
“It’s important to get both, and to get them now if you haven’t already,” said Kawsar Talaat, a Johns Hopkins infectious disease physician and vaccine researcher. “Whether it’s separate or together, it’s just about getting them.”
Does it matter what time of day I get my shots?
That the immune system follows a roughly 24-hour rhythm has been known since the early 1960s. But only in the last decade or two have the circadian clocks that control immune cell activity become a field of intense study, including by vaccine researchers.
Studies in mice have shown that in the morning T cells turn on genes that make up molecules involved in recognizing antigens and churning out armies of T cell clones that can patrol the body looking for more foreign invaders. At night, they produce molecules that silence that response.
“There seems to be a whole program in T cells that makes them very efficient at responding during the day and less efficient at night,” said Nicolas Cermakian, a chronobiologist at McGill University and the Douglas Research Center in Montreal. U PNAS study from 2019his team showed that vaccines delivered during the day induced more T cell activation than those delivered at night.
Data from human studies, at least of the 10 or so conducted so far, gave a more complex picture. U cell research paperr published last year, researchers in China found that among 63 healthcare workers, those who received the injection Sinovac vaccine in the morning produced twice as many antibodies against SARS-CoV-2 as workers who received the sting in the afternoon.
But another study from the UK of 2,784 healthcare workers vaccinated with Pfizer’s or AstraZeneca’s Covid vaccine found that higher antibody levels were seen in people who received the vaccine in the afternoon.
Perhaps the strongest evidence for the AM jab comes from 2016 study influenza conducted in Great Britain – the first large randomized trial of vaccination timing. It found that among 276 older adults, those who received their annual flu shot in the morning had more than three times the antibody response to one of the flu strains than those who got their shot in the afternoon.
However, it is still too early and the data too scarce to draw any rules or recommendations. While it is clear that the immune system responds differently to vaccines at different times of the day, it remains unknown whether or not these improvements translate into better protection against the viral threat. And different types of vaccines may have their own biologically optimized time. Still, Chermakyan said, it’s worth studying. Because adjusting the timing of vaccinations can be a simple and inexpensive way to get the most out of currently available vaccines, especially in the elderly who tend to have weakened immune responses.
“Even a two-fold improvement for the elderly population could be of great benefit,” he said. “Imagine only needing to get a Covid-19 booster once a year, instead of every five or six months. It would make a huge difference in terms of cost and in terms of making it easier for people to stay protected for longer.”
With SARS-CoV-2 continues to evolveand the vaccines most commonly used in the US offer only short-term protection against Covid-19, this is the strategy of the vaccine manufacturers and regulators thinking about the future of boosters may need to be considered. But for now, Chermakian said, you should worry less about what time of day to schedule your vaccination appointment and more about getting a good night’s sleep before it.
“Getting a good night’s sleep in the days before the vaccine is one thing people should do to get a better response,” he said. “We know that a good rest is a big plus.”
Are we forever going to have to get Covid boosters every six months and flu shots every year?
No one can predict the future, but public health officials are beginning to look ahead to what a long-term vaccination strategy for our multi-respiratory virus reality might look like. If the researchers succeed the long-elusive universal flu vaccine approach, it would certainly be a game changer. But Crotty’s latest work suggests there may be more technologically simple ways to induce people’s immune systems to evolve all the antibodies they could ever need.
In the newspaper published last month in the journal Nature, Crotty and his colleagues found that if they inoculated rhesus monkeys with a modest amount of HIV protein slowly, over 12 days, that six months later, some of the animals’ B cells were still actively working to build immunity to HIV . Specifically, they saw sustained activity of B cells called germinal centers, which are sort of like the drivers of antibody evolution in the body. These cells stored those bits of protein and passed them on, learning from them and developing a diverse beast of memory B cells that produce antibodies in the background.
“Mimicking a viral infection by dosing over a longer period of time helps the vaccine engage more of the immune system—it does a much better job of recruiting rare B cells with rare antigen-recognition properties,” Crotty said.
This approach can be overkill for many pathogens that are fairly easily recognized by the immune system. But for bugs that cover their key regions or mutate very quickly, like HIV, influenza and to some extent SARS-CoV-2, then a longer vaccine dose could help overcome this, giving the body’s immune system more time to come find more potential ways to see the virus.
“We wanted to test whether or not exposure time matters, and it turns out it can,” Crotty said. “For me, the take-home message was that we helped uncover a process that we think happens quite regularly and just hasn’t been realized or observed.”
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