We’ll Probably Need Booster Shots for Covid-19. But When? And Which Ones?

As the nation moves closer to President Biden’s goal of 70 percent vaccination rates, many people wonder how long their protection will last.

Right now, scientists are asking a lot of questions about Covid-19 booster vaccinations, but they don’t have many answers yet. The National Institutes of Health recently announced that they have started a new clinical trial of fully vaccinated people – with an approved vaccine – to see if a booster of the Moderna syringe increases their antibodies and protects against infection with the virus extended.

Although many scientists estimate that the US-approved vaccines Pfizer-BioNTech, Moderna, and Johnson & Johnson will last at least a year, no one knows exactly. It is also unclear whether emerging variants of the coronavirus will change our vaccination needs.

“We’re breaking new ground here when it comes to boosters,” said Dr. Edward Belongia, a physician and epidemiologist at the Marshfield Clinic Research Institute in Marshfield, Wisconsin.

Different pathogens affect our immune system in different ways. With some diseases, such as measles, a one-time illness leads to lifelong protection against further infection. But with other pathogens, our immune defense declines over time.

In some important ways, vaccines mimic natural infections – without actually getting sick. Measles vaccines can induce lifelong immunity. Tetanus vaccines, on the other hand, create defenses that fade year after year. The Centers for Disease Control and Prevention recommends getting a tetanus booster once every decade.

And sometimes the virus can change itself, so a booster is needed to create a new, bespoke defense. Influenza viruses are so changeable that they need a new vaccine every year.

The short answer is that we can’t be sure yet because people were vaccinated in large numbers just a few months ago.

“Even in the studies, we don’t know what the immune response is like a year later,” said Dr. Kirsten Lyke, vaccine expert at the University of Maryland School of Medicine and director of the NIH booster study.

But the first signs are encouraging. In vaccine trials, researchers have drawn blood from volunteers and measured their levels of antibodies and immune cells that target the coronavirus. The levels are going down, but gradually. It is possible that with this slow decline, vaccination protection will remain strong for a long time. People who were previously infected and then received the vaccine can enjoy even more permanent protection.

“I think there is a real possibility that immunity to the original strain could last for years,” said Dr. Belongia.

If this possibility is confirmed, Covid-19 boosters may not be required for years. But that’s a big if.

Possibly. Scientists have already established that vaccines with different technologies can vary in their effectiveness. The most powerful vaccines include Moderna and Pfizer-BioNTech, both of which are based on RNA molecules. Inactivated virus-based vaccines, such as those from Sinopharm in China and Bharat Biotech in India, have proven to be slightly less effective.

It’s not entirely clear why that is, said Scott Hensley, an immunologist at the University of Pennsylvania. RNA vaccines are relatively new and so the immunity they induce has not been thoroughly studied. In his own research on mice given different types of flu vaccines – some with RNA and others with inactivated viruses – Dr. Hensley made a similar difference. The amount of antibodies produced by the two vaccines was “grossly different,” he said.

It is possible that protection from the less effective Covid-19 vaccines may wear off faster. Sinopharm’s vaccine may already show signs of this decline. Clinical studies show an effectiveness of 78 percent. But the United Arab Emirates and Bahrain are already offering boosters to people who have received the Sinopharm vaccine to boost their declining immunity.

Scientists are looking for biological markers that could show when protection from a vaccine is no longer sufficient to hold back the coronavirus. It is possible that a certain level of antibody marks a threshold: if your blood is above this level you are in good shape, but if you are below you are at greater risk of infection.

Some preliminary studies suggest that these markers – known as correlates of protection – exist for Covid-19 vaccines. Research is being carried out to find them.

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June 6, 2021, 2:38 p.m. ET

“That will teach us a lot,” says Dr. H. Clifford Lane, Associate Director, Clinical Research and Special Projects, National Institute of Allergy and Infectious Diseases.

We may need boosters to block variants, but that’s not yet clear.

The emergence of variants in recent months has accelerated research on boosters. Some variants have mutations that caused them to spread quickly. Others carry mutations that could affect the effectiveness of approved vaccines. But at this point in time, scientists have little evidence of how existing vaccines work against different variants.

Last month, for example, researchers in Qatar published a study of the Pfizer BioNTech vaccine, which was given to over a quarter of a million of the country’s residents between December and March.

Clinical studies showed that the vaccine was 95 percent effective against the original version of the coronavirus. But a variant called Alpha, which was first identified in the UK, cut its effectiveness to 89.5 percent. A variant first identified in South Africa, known as Beta, further reduced the vaccine’s effectiveness to 75 percent. However, against both variants, the vaccine was 100 percent effective in preventing serious, critical, or fatal illnesses.

Just because a variant can bypass existing vaccines doesn’t mean it becomes a widespread problem. Beta, for example, has remained rare in countries with strong vaccine programs like Israel, the UK, and the United States. If beta stays infrequent, it doesn’t pose a serious threat.

But evolution still has a lot of leeway to play with the coronavirus. Scientists cannot rule out the possibility that new variants will emerge in the coming months that will spread quickly and resist vaccines.

“It is clear that variants are inevitable,” said Dr. Grace Lee, Associate Chief Medical Officer, Practice Innovation and Infectious Disease Doctor at Stanford Children’s Health. “I think the question is how effective are they going to be?”

Its not clear yet. Some scientists suspect that a high immune response to the original version of the coronavirus also provides adequate protection against variants. But it is also possible that a vaccine that specifically thwarted one variant might be more effective.

Pfizer has made an attempt to test both options. Some volunteers who have already received two doses of their vaccine will be given a third dose of the same vaccination as a booster. In the same study, the researchers will give other volunteers an experimental booster designed to protect against the beta variant.

“Based on what we’ve learned so far, we currently think that until we see a decrease in SARS-CoV-2 circulation and Covid-19 disease, we think it likely that a third dose, a Increasing our vaccine, within 12 months of vaccine administration, will likely be needed to protect against Covid-19, “said Jerica Pitts, director of global media relations at Pfizer.

Possibly. In fact, much research on other diseases suggests that switching vaccines may increase the booster dose. “This is a proven concept from before Covid,” said Dr. Lyke.

Dr. Lyke and her colleagues are testing this mix-and-match option for boosters as part of their new study. They are recruiting volunteers who have been fully vaccinated with any of three US approved vaccines – Johnson & Johnson, Moderna, and Pfizer-BioNTech.

All volunteers receive a Moderna booster. The researchers will then observe how strong an immune response it creates.

It is possible that other vaccines that are still in clinical trials may work even better as Covid boosters. For example, Novavax and Sanofi are both conducting clinical trials of vaccines made from viral proteins in the United States. Dr. Lyke and her colleagues designed their study so that they could add more such vaccines later.

“We are working behind the scenes on other contracts so we can bring additional boosters into the study,” she said. These additional boosters can also include those tailored to variants, such as the one developed by Pfizer-BioNTech.

Other mixed booster studies are also ongoing. In the UK, scientists are giving volunteers vaccines from AstraZeneca, CureVac, Johnson & Johnson, Moderna, Novavax, Pfizer-BioNTech and Valneva as boosters. ImmunityBio is testing its vaccine in South Africa as a booster for the Johnson & Johnson vaccine, while Sanofi prepares to test its vaccine as a booster for those of several other companies.

The NIH study could start delivering results as early as the next few weeks. If fading vaccines and rising variants lead to an outbreak of new infections this winter, Dr. Lyke have data to share with policy makers.

“It was vital for us to get a response as soon as possible,” she said. “We just don’t have this luxury of time.”

Dr. Hensley says it is wise to prepare for the possibility that boosters will be needed. But he hoped they didn’t detract from the urgent need to give billions of people around the world first doses.

“If more people are protected immediately, the virus will have fewer hosts to infect and fewer opportunities to develop into new variants,” he said.

“I want these vaccines to go global because I want to protect people all over the world,” added Dr. Hensley added. “But even if you only take care of yourself, you should also stand behind these efforts, because this is the only way to end the pandemic and limit the development of variants.”

Noah Weiland contributed the reporting.

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