There are growing concerns that COVID-19 vaccines do not offer sufficient protection against new variants of the SARS-CoV-2 virus. Israel has already started to offer booster shots of the Pfizer vaccine to at-risk adults, and the United States is in talks with Pfizer about introducing these shots for the most vulnerable.

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There has been talk of a third dose for some COVID-19 vaccines. Why might vaccine boosters be necessary, and what are the questions researchers are yet to answer about them? Image credit: Jens Schlueter/Getty Images

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There is growing evidence that people who have received COVID-19 vaccines are less likely to become infected with the virus that causes this disease and that if they do, they are less likely to have symptoms of severe illness.

However, evidence is also emerging that existing vaccines may offer less protection against new variants of SARS-CoV-2, such as the delta variant.

One study, for example, showed that 95% of people who received both doses of the Pfizer-BioNTech or Oxford-AstraZeneca COVID-19 vaccine had a weaker immune response to the delta variant than to previous strains.

People who received just one dose of either vaccine had a very weak immune response, which suggests that a single dose of one of these vaccines does not offer adequate protection.

The Health Ministry of Israel also released a statement saying that the effectiveness of the Pfizer-BioNTech vaccine in preventing symptomatic COVID-19 fell to just 64% at 6 months post-vaccination. It noted, however, that two doses of Pfizer are still able to prevent serious illness in 93% of cases.

As of yet, the U.S. has made no decision as to whether they will approve access to booster vaccines. However, the Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA) said in a joint statement that they are “prepared for booster doses if and when the science demonstrates that they are needed.”

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Vaccine boosters are additional vaccine doses that should provide extra protection against disease, as the effects of some vaccines may wear off over time.

Vaccine boosters are common for many viral infections, including the flu, which requires a booster every year, and tetanus, diphtheria, and pertussis (DTaP), for which a booster is necessary every 10 years.

For some vaccines, receiving smaller doses more often is more effective than getting a single large vaccine dose.

This approach allows the immune system to build its immune response sustainably. When the immune system remembers certain antigens that previously activated it, it can respond much quicker the next time it encounters them.

Although many vaccine boosters are identical to the previous doses, some are modified to enhance their efficacy. The flu vaccine, for example, changes every year to respond more effectively to new mutations of the influenza virus.

Article summary:

There are generally two reasons why people might consider vaccine boosters. The first is that immunity naturally wanes over time. Without repeated exposure to certain antigens, the immune system may become less able to prevent infection or disease. Vaccine boosters help the immune system maintain a protective response.

“Another reason we may need booster vaccinations is viral variants,” a spokesperson from the COVID-19 Vaccine Team at the University of Oxford told Medical News Today. They went on to explain:

“Some variants have evolved to avoid some parts of our immune response, which means they can more easily infect those who have an existing immune response to the virus — i.e., those who have been previously infected or vaccinated. However, the virus cannot avoid all parts of our immune response. A booster vaccination is helpful, as it can improve the parts of our immune response the viral variant cannot avoid.”

“Alternatively, we can use a booster vaccine that specifically targets the viral variant. This works by producing a new immune response to the parts of the virus which have changed from the original vaccine whilst also improving the existing immune response against the unchanged parts of the virus, which also should help protect against other variants,” they added.

As national agencies such as the CDC note, existing data indicate that most COVID-19 vaccines produce a strong immune response that offers sufficient protection against the SARS-CoV-2 virus.

However, it remains unclear for how long COVID-19 vaccines — in the current dosages — continue to offer protection.

Nevertheless, booster doses might benefit older individuals or those with a weak immune system, as their bodies may not have generated a strong enough immune response after the initial vaccines.

“Based on current data, for people who respond well to the vaccine, it looks like immunity remains strong for over 12 months and works even against the new variants,” Dr. Richard Stanton, a reader in the Division of Infection and Immunity at Cardiff University in the United Kingdom, told MNT.

“My personal opinion is, therefore, that we don’t need to be too worried about boosting them yet,” he said.

However, he cautioned:

“Where we do need to be careful is in people who don’t respond well to the vaccine. There are lots of vulnerable groups in society who fall into this category, and we know from other vaccines that older people sometimes don’t have the same length of immunity as younger people. I think we should be looking carefully at whether it’s appropriate to give them a boost.”

“If that boost can be done with a vaccine that matches the newer strains, that will be even better — but that’s difficult because the virus is constantly changing, and it takes time to generate the vaccine, so we’re always playing catch-up. A boost with the older vaccine is still OK though — they do work against the new variants to prevent serious disease, especially if the immune response is strong,” he also noted.

Dr. Jessica Justman, associate professor of medicine in epidemiology at Columbia Mailman School of Public Health, further explained that “[b]ooster shots might be most beneficial for those who have medical conditions — such as some solid organ transplant recipients (e.g., kidney transplant) and some individuals with autoimmune diseases (e.g., lupus) — that prevent them from developing an effective immune response after the first round of vaccination.”

However, she added, “[w]e would first need evidence that a booster shot for these individuals is safe and effective.”

Other scientists say that the opportunity cost of not providing booster vaccines outweighs the lack of research underpinning their use.

In an interview with the BMJ, Prof. Anthony Harnden of the Joint Committee on Vaccination and Immunisation in the U.K. expressed the opinion that the U.K. is likely to roll out booster vaccines and that annual boosters might be necessary for some time.

“Scientifically, there is nothing controversial about additional booster vaccinations; they work in very much the same way as a second vaccine in a two-vaccine schedule,” the Oxford COVID-19 Vaccine Team spokesperson told MNT.

“The debate around additional vaccines is whether they are needed at this stage or [whether] vaccine doses are better off being used elsewhere — particularly in poorer countries, as highlighted recently by Sir Andrew Pollard in an article in The Times newspaper,” they added.

Sir Andrew Pollard, director of the Oxford Vaccine Group at the University of Oxford, wrote that the main purpose of vaccines is to “keep people out of hospital.”

As vaccines seem to reduce hospitalizations with COVID-19 significantly, and experts predict that vaccine supplies will be limited for the foreseeable future, Sir Andrew argues that it is important to prioritize those who have not yet had even a single shot before providing boosters to others.

Some people even question whether it is morally right to give booster shots to those who have already been vaccinated when many people, especially those in developing countries, have not received even one shot and are thus at a higher risk of infection.

Others question the need for a third vaccine.

In response to vaccination, T cells and B cells, which are part of the body’s immune system, react by building up long lasting immunity to the virus. B cells are the immune system’s “memory cells,” and they produce antibodies that bind to the virus. T cells help B cells produce these antibodies. Some T cells also kill infected cells.

So far, one study — which has not yet undergone peer review but appears on an online preprint service — has suggested that people who have recovered from mild COVID-19 experience a lasting T-cell response.

Another study that features on a preprint service ahead of peer review found that, in people recovering from symptomatic or mild COVID-19, B cells can produce new antibodies that specifically target new variants of SARS-CoV-2.

The same lasting immune response is likely to occur following a COVID-19 vaccine, some experts argue.

Research investigating vaccine booster doses is currently underway. Some early studies, however, suggest that although current vaccines offer some protection against existing variants, this may decrease as the virus mutates and new variants emerge.

For example, one study — shared online in preprint form — found that people fully immunized with the Pfizer-BioNTech or Oxford-AstraZeneca vaccines had a weaker antibody response upon exposure to the delta and beta variants of SARS-CoV-2, which scientists first identified in India and South Africa, respectively. This, say the researchers, means that booster vaccines based on updated variants may be necessary over time to prevent infections.

Another study — which also appears online via a preprint service — found that after receiving the one recommended dose of the Johnson & Johnson vaccine, people showed immunity against multiple SARS-CoV-2 variants, including the delta variant.

The researchers noted, however, that the immune response to the delta variant appeared to be weaker than that to previous variants of SARS-CoV-2.

On July 8, 2021, Pfizer and BioNTech released a statement saying that giving booster doses of their vaccine 6 months after the second dose produces an immune response to several variants of the virus that is 5–10 times more potent than that following the second dose. They state, however, that they are creating an updated version of the vaccine to target the delta variant.

Many clinical trials are underway to learn more about the duration of immunity in regular vaccine regimens, how it changes after a third dose, and what happens if that third dose is a better match for new variants. As most of these trials have just begun, results will not be available for some time, though.

For example, the National Institutes of Health (NIH) launched a trial in June 2021 to determine the safety and effectiveness of a third vaccine dose from a different brand. Researchers will follow the participants for a year after their third vaccination, meaning that the results of this study will emerge by mid-2022 at the earliest.

The results of this trial will inform public policy decisions on whether booster shots are necessary to keep up with the virus as new variants emerge. Similar trials are also underway at the University of Washington and the University of Southampton in the U.K.

Until scientists collect and publish the results from these studies, whether booster vaccine doses are truly helpful in the fight against COVID-19 remains an open question. For now, experts recommend taking a full course of whatever COVID-19 vaccine is available in a person’s country.

“We have learned a great deal about COVID vaccines in a very short time, but there’s still plenty we don’t know yet,” Dr. Justman told MNT.

Some of the questions that remain unanswered, she noted, include:

  • “Is it better to boost with the same vaccine (a homologous boost) that was initially given or with a different vaccine (a heterologous boost)?
  • What is the best method to measure the different components of the immune response after vaccination?
  • For those who take immunosuppressive medications, would a brief reduction in these medications be better than or just as good as a booster?
  • What dose should a booster be, and at what time interval?
  • Is a booster safe in all age groups?
  • [Are there] any groups who may not do well with a booster?
  • What age group would benefit most from a booster?”

These are all questions that researchers are doing their best to address as soon as possible. This does not change the fact, said Dr. Justman, that: “[t]he most important booster is to vaccinate as many people as possible right now, both here in the U.S. and globally.”

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