Each new dose of vaccine given may help even the previously infected fight off emerging COVID-19 variants


A small, early study suggests that people who’ve already encountered SARS-CoV-2 may gain a big boost against COVID-19 if they get just one dose of the Pfizer vaccine – and that protection may extend to new viral variants.

The study “supports the notion that vaccine effectiveness, even against emerging neutralization-resistant [variants], may be improved following an additional vaccine boost,” said a team led by Richard Urbanowicz, senior virology research fellow at the University of Nottingham in England. His team published their findings Aug. 10 in the journal Science Translational Medicine.

The new study was small – just 45 health care workers, including 20 who had tested positive previously for SARS-CoV-2 and 25 who had not.

Their COVID-19 antibody status was tracked via blood samples beginning in April 2020, and when the Pfizer vaccine became available everyone received a first dose, followed by a second dose 10 weeks later.

According to a journal news release, getting the second dose of the vaccine was especially important, boosting “both the potency and breadth of neutralizing antibodies against SARS-CoV-2.” What’s more, this effect was magnified to an even higher level in people who’d already been infected with the new coronavirus, the researchers said.

There was one more potential benefit. Even though the Pfizer shots that previously infected people received were formulated to fight the original (2019) variant of the virus, blood samples from people who’d had an encounter with COVID-19 were shown to “neutralize” the later Beta form of the virus, as well.

That suggests that each new dose of vaccine given may help even the previously infected fight off emerging COVID-19 variants, the study authors said, although data on the new (and most infectious) Delta variant is lacking.

Two experts unconnected to the study said the data is encouraging, but inconclusive.

The study provides “reasonable evidence that continued immunogenic challenge [vaccine], even in previously infected patients, is beneficial and it suggests that two vaccines is more beneficial than one,” said Dr. Theodore Maniatis, medical director at Staten Island University Hospital, in New York City. It also suggests “that this repeated immunogenic challenge may somehow spread to cover new variants.”

Still, he cautioned that the study’s population was small and it “did not test the antibody level and function against all variants [including Delta].”

It was also largely based on lab tests, Maniatis added, “meaning that there is no definite proof that these findings will decrease infections in humans.”

Dr. Teresa Murray Amato is chair of emergency medicine at Long Island Jewish Forest Hills, also in New York City. She said the new study also suggests that “there may be some data to suggest that a ‘booster’ vaccine for those fully vaccinated may also show a better antibody response,” versus simply getting the initial two doses of the Pfizer vaccine.

Maniatis stressed that “this is the type of article that one performs, analyzes, and then creates bigger studies with a greater number of patients and eventual clinical trials.”

Amato agreed.

“There are ongoing studies being done to understand the best, most effective and safest way to vaccinate all eligible Americans,” she said. In the meantime, “make sure to ask your doctor if you have any questions regarding the COVID vaccine.”

There is reason to be confident about the protection offered by current covid vaccines, says Eleanor Riley, professor of immunology and infectious disease at the University of Edinburgh. Referring to Marr, who had a major stroke in 2013, she says: “A man over 60 with significant prior health problems got a mild, flu-like illness and was back at work in a week.”

Warning signs
Data up to 4 August from Imperial College London’s React study found that people who said they had received two vaccine doses were half as likely to test positive for covid-19, adjusting for other factors such as age and whether or not they had symptoms.3 The researchers estimated a 50-60% lower risk of infection from the delta variant if a person was double vaccinated.

The picture emerging from various countries does, however, suggest that vaccinated people are more likely to experience symptoms after catching the delta variant compared with earlier forms of the virus.

Data published by the Israeli government suggest that the Pfizer BioNTech jab’s efficacy against symptomatic infection fell from 94% to 64% after the delta variant began spreading in the country.4

Figures from Public Health Scotland published in the Lancet also show a drop in protection against symptomatic illness,5 from 92% against the alpha variant, which was first detected in the UK, to 79% against delta among people with two doses of the Pfizer BioNTech vaccine. For the Oxford AstraZeneca vaccine, the reduction was from 73% to 60%. Data from Canada, yet to be peer reviewed, also show a drop in efficacy.6

It’s difficult to compare data from multiple countries because they all have different protocols determining when people become eligible for a covid-19 test, for example. And symptomatic infection can take many forms, from very mild to severe illness.

But Riley points out that the PHE data to date are consistent with estimates that suggest—despite these drops in efficacy—vaccines in use in the UK (Pfizer BioNtech, AstraZeneca, and Moderna) all reduce the risk of death by more than 85%, regardless of variant.

What about transmission?
A lingering question is to what extent the vaccines may be losing effectiveness at preventing onward transmission from people who become infected. After all, each of the new variants is characterised by increased transmissibility compared with the original (wild type) SARS-CoV-2.

Akiko Iwasaki of Yale University says we won’t know unless we can get more observational studies following household contacts.

One yet to be peer reviewed study looked at a single outdoor wedding near Houston, Texas, in April where all 92 guests were required to be fully vaccinated.7 A couple who had travelled from India later tested positive for delta, with one dying a month later. Of the people they interacted with at the wedding, four became ill with delta. One required monoclonal antibody treatment, but all four survived.

A recently released report from the US Centers for Disease Control and Prevention suggests that the viral load of vaccinated people infected with the delta variant is similar to that of unvaccinated people.8 People remain less likely to become infected in the first place when they have been vaccinated, however.9

Neutralising antibodies
It’s not yet clear how the body’s immune system fights SARS-CoV-2. Without knowing for sure what the correlates of protection are, it’s hard to say why a vaccine may be less effective against variants. Evidence is accumulating, however, that the ability of antibodies to neutralise the delta variant is reduced compared with, say, the alpha variant.

A study published in Nature found that antibodies in blood samples (sera) from convalescent patients up to 12 months post-infection were four times less effective at neutralising the delta variant than the alpha variant.10 Sera from people who had only a single dose of the Pfizer BioNTech or Oxford AstraZeneca vaccines “barely” inhibited delta, wrote the authors.

They did, however, see a neutralising response in sera from almost all people who had received two doses of a vaccine.

Another study on neutralising antibodies, published in the Lancet, found that, following two doses of the Oxford AstraZeneca vaccine, the number of people who had quantifiable antibodies against delta was significantly lower, at 62% (39 of 63), than against the original wild type SARS-CoV-2 (100% of participants).

That may sound worrying, but Akiko Iwasaki, professor of immunobiology and molecular, cellular, and developmental biology at Yale University, says there is reason to be hopeful that people who have had two vaccine doses can still fend off severe disease when infected by delta. This is likely to be in part because of other aspects of the immune system, such as T cells that stimulate B cells to produce antibodies or killer T cells that destroy infected cells in the body.11

She also points out that a reduction in neutralising antibodies does not necessarily mean that antibodies will fail to have an impact. “I assume that the reason we can still prevent severe disease from the delta variant is that we are generating enough antibody response against the spike protein,” she says.

Laboratory based analysis of antibody and T cell responses to the original SARS-CoV-2 virus and multiple variants coauthored by Iwasaki and yet to be peer reviewed found that, against delta, vaccination still prompted neutralising antibodies.12 There were, however, more antibodies in people who had caught covid-19 before vaccination.

The bottom line is that delta—a variant with distinct mutations making it much more transmissible, blunting immune protection as much as 10-fold—poses a challenge to the vaccines currently used. But in most people the vaccine induced levels of neutralising antibodies are large enough that even a 10-fold drop keeps them well protected.

So, while it’s sobering to see cases occurring in fully vaccinated people, their protection is holding up well, as judged by numbers of hospital admissions and fatalities relative to what might have been. As Iwasaki puts it: the message should still be to get vaccinated as soon as possible.

Manufacturers confident
“We haven’t seen any evidence that the circulating variants result in a loss of protection provided by the Pfizer BioNTech covid-19 vaccine (BNT162b2) in our laboratory studies,” a spokeswoman for Pfizer told The BMJ.

AstraZeneca said in a statement: “Real world data from Public Health Scotland published in the Lancet, reaffirmed the AstraZeneca covid-19 vaccine was effective in reducing the risk of SARS-CoV-2 infection and hospital admissions because of the delta variant but at a slightly lower level compared with the alpha variant.”

Moderna has said tests show that its vaccine continued to produce neutralising activity against multiple variants of concern, including delta,13 while a Janssen spokesperson told The BMJ, “Against the emerging variants of concern, neutralising antibodies were higher against the delta variant than what was observed for the beta variant in South Africa.”

Despite this universal confidence, however, Pfizer, for one, is at work on an updated version of its vaccine, targeting the delta variant specifically. The company hopes this will enter clinical studies in August.

reference link: https://www.bmj.com/content/374/bmj.n1960

More information: Richard A Urbanowicz et al, Two doses of the SARS-CoV-2 BNT162b2 vaccine enhances antibody responses to variants in individuals with prior SARS-CoV-2 infection, Science Translational Medicine (2021). DOI: 10.1126/scitranslmed.abj0847


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