COVID-19: Pfizer third dose vaccine could dramatically boost immunity and maybe help ward off the latest worrisome coronavirus mutant

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Pfizer is about to seek U.S. authorization for a third dose of its COVID-19 vaccine, saying Thursday that another shot within 12 months could dramatically boost immunity and maybe help ward off the latest worrisome coronavirus mutant.

Research from multiple countries shows the Pfizer shot and other widely used COVID-19 vaccines offer strong protection against the highly contagious delta variant, which is spreading rapidly around the world and now accounts for most new U.S. infections.

Two doses of most vaccines are critical to develop high levels of virus-fighting antibodies against all versions of the coronavirus, not just the delta variant – and most of the world still is desperate to get those initial protective doses as the pandemic continues to rage.

But antibodies naturally wane over time, so studies also are underway to tell if and when boosters might be needed.

On Thursday, Pfizer’s Dr. Mikael Dolsten told The Associated Press that early data from the company’s booster study suggests people’s antibody levels jump five- to 10-fold after a third dose, compared to their second dose months earlier.

In August, Pfizer plans to ask the Food and Drug Administration for emergency authorization of a third dose, he said.

Why might that matter for fighting the delta variant? Dolsten pointed to data from Britain and Israel showing the Pfizer vaccine “neutralizes the delta variant very well.” The assumption, he said, is that when antibodies drop low enough, the delta virus eventually could cause a mild infection before the immune system kicks back in.

But FDA authorization would be just a first step – it wouldn’t automatically mean Americans get offered boosters, cautioned Dr. William Schaffner, a vaccine expert at Vanderbilt University Medical Center. Public health authorities would have to decide if they’re really needed, especially since millions of people have no protection.

“The vaccines were designed to keep us out of the hospital” and continue to do so despite the more contagious delta variant, he said. Giving another dose would be “a huge effort while we are at the moment striving to get people the first dose.”

Hours after Pfizer’s announcement, U.S. health officials issued a statement saying fully vaccinated Americans don’t need a booster yet.

U.S. health agencies “are engaged in a science-based, rigorous process to consider whether or when a booster might be necessary,” the FDA and Centers for Disease Control and Prevention said in a joint statement. That work will include data from the drug companies, “but does not rely on those data exclusively,” and any decision on booster shots would happen only when “the science demonstrates that they are needed,” the agencies said.

Currently only about 48% of the U.S. population is fully vaccinated – and some parts of the country have far lower immunization rates, places where the delta variant is surging. On Thursday, Dr. Rochelle Walensky, the CDC director, said that’s leading to “two truths” – highly immunized swaths of America are getting back to normal while hospitalizations are rising in other places.

“This rapid rise is troubling,” she said: A few weeks ago the delta variant accounted for just over a quarter of new U.S. cases, but it now accounts for just over 50%—and in some places, such as parts of the Midwest, as much as 80%.

Also Thursday, researchers from France’s Pasteur Institute reported new evidence that full vaccination is critical.

In laboratory tests, blood from several dozen people given their first dose of the Pfizer or AstraZeneca vaccines “barely inhibited” the delta variant, the team reported in the journal Nature. But weeks after getting their second dose, nearly all had what researchers deemed an immune boost strong enough to neutralize the delta variant – even if it was a little less potent than against earlier versions of the virus.

The French researchers also tested unvaccinated people who had survived a bout of the coronavirus, and found their antibodies were four-fold less potent against the new mutant. But a single vaccine dose dramatically boosted their antibody levels—sparking cross-protection against the delta variant and two other mutants, the study found.

That supports public health recommendations that COVID-19 survivors get vaccinated rather than relying on natural immunity.

The lab experiments add to real-world data that the delta variant’s mutations aren’t evading the vaccines most widely used in Western countries, but underscore that it’s crucial to get more of the world immunized before the virus evolves even more.

Researchers in Britain found two doses of the Pfizer vaccine, for example, are 96% protective against hospitalization with the delta variant and 88% effective against symptomatic infection. That finding was echoed last weekend by Canadian researchers, while a report from Israel suggested protection against mild delta infection may have dipped lower, to 64%.

Whether the fully vaccinated still need to wear masks in places where the delta variant is surging is a growing question. In the U.S., the CDC maintains that fully vaccinated people don’t need to. Even before the delta variant came along, the vaccines weren’t perfect, but the best evidence suggests that if vaccinated people nonetheless get the coronavirus, they’ll have much milder cases.

“Let me emphasize, if you were vaccinated, you have a very high degree of protection,” Dr. Anthony Fauci, the U.S. government’s top infectious disease expert, said Thursday.

In the U.S., case rates have been rising for weeks and the rate of hospitalizations has started to tick up, rising 7% from the previous seven-day average, Walensky told reporters Thursday. However, deaths remain down on average, which some experts believe is at least partly due to high vaccination rates in people 65 and older—who are among the most susceptible to severe disease.


AS THE UK and some other wealthy countries edge towards a fully vaccinated adult population, a new question is being asked: will people need booster vaccines against covid-19?

The answer depends on three unknowns: how quickly immunity fades, whether current vaccines protect against existing and future coronavirus variants, and whether booster shots actually work. There are also issues of vaccine nationalism and equity to consider (see “Boost or bust?”).

60m Doses of vaccine ordered by the UK for possible booster campaign

Booster vaccines are routinely used for some infectious diseases, either to top up immunity or to update it for new virus variants. Tetanus boosters, for example, are recommended every 10 years to renew waning immunity, and annual flu shots are designed to protect against that season’s variants.

Israel is ahead of the curve. The country has already vaccinated more than 80 per cent of over-16s and announced last month that it would run a booster campaign in October. Prime Minister Benjamin Netanyahu said in a televised address that Israel had secured 16 million extra doses of the Pfizer/BioNTech and Moderna vaccines to immunise its under-16s and boost everybody else.

Other countries whose immunisation programmes are progressing well are more circumspect. The UK is on course to have offered a first vaccine dose to its adult population by the end of July, and is now weighing up an autumn booster campaign. “We haven’t made any decisions on this yet,” says Anthony Harnden at the University of Oxford, deputy chair of the Joint Committee on Vaccination and Immunisation (JCVI), which advises UK health departments.

The UK has ordered a further 60 million doses of the Pfizer/BioNTech vaccine in preparation for a possible booster campaign but “we can’t make the decision until we’ve seen all the evidence”, says Harnden. It is possible that the JCVI will recommend a booster for the vulnerable groups that were first in line for a vaccine in the UK, he says. The JCVI will announce its decision as soon as it is made.

The US has also yet to make a call. A statement from the Centers for Disease Control and Prevention, which oversees the US vaccination programme, says: “The need for and timing for COVID-19 booster doses have not been established. No additional doses are recommended at this time.”

The first piece of evidence needed is how quickly immunity fades after a vaccine. “I don’t think we know, because we’ve not really got the data on what happens nine months after a [covid-19] vaccine,” says virologist Deenan Pillay at University College London (UCL).

That information should be forthcoming soon, says Alex Richter, an immunologist at the University of Birmingham, UK. Various research projects on the duration of immunity in healthcare workers are due to report results over the next few weeks, she says. For example, the SIREN study, which is following more than 44,000 staff at 135 hospitals across the UK, is looking at the duration of immunity after having a Pfizer/BioNTech vaccine. T

he first vaccines were given in December and a six-month assessment is due out in June, says Richter. “If data at that point is showing significant waning [of antibodies], then that will influence policy,” she says. “Most healthcare workers are really fit and healthy, so if they are not hanging onto their antibodies then it’s highly likely we’re going to need to be vaccinating in the autumn with a booster.”

Another consideration is whether the current vaccines protect against viral variants. If they don’t, then a booster campaign may be needed using shots tailored to protect against specific variants.

According to Harnden, lab studies show that vaccine-induced antibodies remain effective against the B.1.1.7 variant first seen in the UK and the P.1 variant from Brazil, but there are concerns about B.1.351, first identified in South Africa. “We do know that the vaccines are not quite as effective against the South African variant in terms of preventing disease, although they do seem to be pretty good at preventing severe disease, hospitalisations and deaths,” says Harnden.

If any variant proves capable of escaping the immunity conferred by current vaccines, then a variant-busting booster campaign is on the cards, he says.

Inadequate data

Right now, we don’t know if vaccine escape is a genuine danger. “This is a critical question,” says Pillay. “We really need a coherent assessment of the nature of breakthrough infections – in other words, infections that are happening in those who are fully immunised. Is that driven by variants, or is it to do with declining antibody and immunity from the first two doses [of vaccine]?”

A recent study documented two cases of breakthrough infections in a group of 417 fully vaccinated people, due to what seems to be a new variant (NEJM, doi.org/gjsbr9). “That is the level of data we’ve currently got, which is clearly inadequate to determine a major policy,” says Pillay.

Despite the uncertainties, Israel has acted already on this too. It has negotiated an option to buy doses of Moderna’s variant-specific booster vaccines, assuming they are approved. Moderna has two such booster vaccines in clinical trials. One is designed to protect against B.1.351, the other is a combination of this and the firm’s original vaccine. Moderna is also testing booster shots of its initial vaccine and recently announced positive results from two of its trials. Pfizer is also testing booster shots of its first coronavirus vaccine and a variant-specific one.

Another factor to weigh up in relation to variants is an immunological phenomenon called original antigenic sin. This is where an updated vaccine reactivates an earlier immune memory rather than creating a new one. It has been seen with other viral infections including flu, says Anthony Costello at UCL, but whether it will be a problem with the virus that causes covid-19, SARS-CoV-2, remains to be seen. Studies to establish this are urgently needed, says John Moore at Weill Cornell Medicine in New York, because original antigenic sin could render a variant-specific booster campaign pointless.

Booster shots could fail for other reasons. A third dose of viral-vector vaccines like the Oxford/AstraZeneca one could just boost the immune response to the harmless virus used as a vehicle to deliver the active ingredient. “One of the concerns is that we may not be able to augment the antibodies against the [SARS-CoV-2] spike protein,” says Teresa Lambe at the University of Oxford, who worked on the vaccine’s development. She is doing experiments to determine the immune response to a third dose.

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Boost or bust?

Rich countries like Israel and the UK are already buying up tens of millions of extra vaccine doses for potential immunity booster campaigns (see main story), but the strategy could end up making the covid-19 pandemic worse.

As the World Health Organization has repeatedly said, the pandemic can’t end until the whole world is vaccinated.

Unvaccinated populations could act as a source of yet more new variants, and vaccine-resistant variants could push the vaccinated part of the world back to square one.

Rich countries have already bought up far more than their fair share of vaccines, and ordering booster doses just exacerbates that problem.

“When we talk about boosting and revaccination, it’s also important to bear in mind globally what is needed in terms of vaccination access where the progress has been much, much slower,” says Tolullah Oni at the University of Cambridge’s MRC Epidemiology Unit.

“If there’s anything we can see from the tragedy that is playing out in India at the moment it is that, yes, we have to maximally suppress [the virus] locally but also do everything in our power to support vaccination access globally,” she says. “That is a really critical point when we’re talking about how to get out of this pandemic.”

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For this reason and others, it may be preferable to boost people’s immunity with a different vaccine from the one they got the first two times.

There is some evidence that using different vaccines for the first and second dose – a method called heterologous prime-boost vaccination – produces a stronger immune response than using the same vaccine for both.

Russia’ Russia’s

Sputnik V, for example, is a heterologous prime-boost vaccine and the latest real-world figures from the country show that it is 97.6 per cent effective, which would make it the most effective covid-19 vaccine in the world.

Ongoing experiments in the UK are examining the effects of mixing and matching first and second vaccine doses, and the results could inform decisions on a booster campaign, says Harnden.

All of these uncertainties emphasise an important point that has been largely forgotten amid vaccine euphoria, says Costello. “The idea that you can continually boost [immunity] is both logistically difficult and may be immunologically difficult.” We may face breakthrough infections that can’t be vaccinated against and so we will still need interventions such as masks, ventilation and social distancing. “Vaccination has been great, but it’s not going to solve the problem in its entirety,” says Costello.

reference link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121557/


Journal information: Nature

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