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Evidence for Reduced Antibody Protection Against SARS-CoV-2 Variants

Testing and vaccination – these are the pillars on which humanity is trying to get a grip on the Coronavirus pandemic. Although it is taking longer than many had expected, it is believed that it is only a matter of time before we are all vaccinated and thus protected.

However, time is also working for the virus, which has now mutated several times, with variants B.1.1.7 from the United Kingdom, B.1.351 from South Africa and P.1 from Brazil spreading rapidly. These viruses have mutations in the so-called spike protein, the structure on the surface of the virus that is responsible for attachment to host cells. At the same time, the spike protein is also the major target of the immune response. Antibodies generated in response to SARS-CoV-2 infection or vaccination bind to the spike protein, thereby blocking the virus.

A team led by Markus Hoffmann and Stefan Pöhlmann of the German Primate Center – Leibniz Institute for Primate Research and Jan Münch of the Ulm University Medical Centre has found that the SARS-CoV-2 variants B.1.351 and P.1 are no longer inhibited by an antibody used for COVID-19 therapy. In addition, these variants are less efficiently inhibited by antibodies from recovered patients and vaccinated individuals. Thus, convalescence from COVID-19 as well as vaccination may offer only incomplete protection against these mutant viruses (Cell).

SARS-CoV-2 viruses invade lung cells in order to multiply. For the virus to enter a cell, it must first attach to the cell surface. For this, the virus uses its so-called spike protein, which is located on the viral envelope. The spike protein is also the target for therapies and vaccines aimed at preventing the virus from replicating in the body.

At the beginning of the pandemic, SARS-CoV-2 was relatively stable, but recently several viral variants have been detected and are spreading rapidly. Variants B.1.1.7, B.1.351, and P.1, which first appeared in the United Kingdom, South Africa, and Brazil, respectively, have mutations in the spike protein and some are located in areas targeted by currently used antiviral agents and vaccines.

“This is worrisome because the rapid spread of variants that might not be efficiently inhibited by antibodies could undermine our current vaccination strategy,” says Stefan Pöhlmann, an infection biologist at the German Primate Center in Göttingen. Therefore, the team led by Pöhlmann and Münch investigated how effectively the mutant viruses are inhibited by drugs and antibodies.

“We found that certain antiviral agents that block host cell entry and are in (pre)clinical development inhibit the mutant viruses just as well as the original virus. Variant B1.1.7, which is currently spreading rapidly in Germany, was also efficiently inhibited by antibodies, including antibodies induced by vaccination. In contrast, an antibody used for COVID-19 therapy did not inhibit variants B.1.351 and P.1. Moreover, these variants were less well inhibited by antibodies from convalescent or vaccinated individuals, they partially bypassed the neutralizing effect of the antibodies,” says Jan Münch.

The use of the currently available vaccines makes sense and a rapid expansion of the vaccination efforts in Germany is desirable. However, it is possible that vaccination or recovery from COVID-19 may offer reduced protection from SARS-CoV-2 variants B.1.351 and P.1.” Clinical studies must now show the extent to which this fear is true.

“Our findings show that it is important to limit the spread of the virus as much as possible until widespread vaccination is feasible. Otherwise, we risk the emergence of new variants that cannot be effectively controlled by the currently available vaccines” says Markus Hoffmann, first author of the study.


Source: German Primate Center

Vaccine-induced Antibodies May be Less Effective Against Several New SARS-CoV-2 Variants

Rachel Leeson wrote . . . . . . . . .

SARS-CoV-2, the virus that causes COVID-19, has mutated throughout the pandemic. New variants of the virus have arisen throughout the world, including variants that might possess increased ability to spread or evade the immune system. Such variants have been identified in California, Denmark, the U.K., South Africa and Brazil/Japan. Understanding how well the COVID-19 vaccines work against these variants is vital in the efforts to stop the global pandemic, and is the subject of new research from the Ragon Institute of MGH, MIT and Harvard and Massachusetts General Hospital.

In a study recently published in Cell, Ragon Core Member Alejandro Balazs, PhD, found that the neutralizing antibodies induced by the Pfizer and Moderna COVID-19 vaccines were significantly less effective against the variants first described in Brazil/Japan and South Africa. Balazs’s team used their experience measuring HIV neutralizing antibodies to create similar assays for COVID-19, comparing how well the antibodies worked against the original strain versus the new variants.

“We were able to leverage the unique high-throughput capacity that was already in place and apply it to SARS-CoV-2,” says Balazs, who is also an assistant professor of Medicine at Harvard Medical School and assistant investigator in the Department of Medicine at MGH. “When we tested these new strains against vaccine-induced neutralizing antibodies, we found that the three new strains first described in South Africa were 20-40 times more resistant to neutralization, and the two strains first described in Brazil and Japan were five to seven times more resistant, compared to the original SARS-CoV-2 virus.”

Neutralizing antibodies, explains Balazs, work by binding tightly to the virus and blocking it from entering cells, thus preventing infection. Like a key in a lock, this binding only happens when the antibody’s shape and the virus’s shape are perfectly matched to each other. If the shape of the virus changes where the antibody attaches to it – in this case, in SARS-CoV-2’s spike protein – then the antibody may no longer be able to recognize and neutralize the virus as well. The virus would then be described as resistant to neutralization.

“In particular,” says Wilfredo Garcia-Beltran, MD, PhD, a resident physician in the Department of Pathology at MGH and first author of the study, “we found that mutations in a specific part of the spike protein called the receptor binding domain were more likely to help the virus resist the neutralizing antibodies.” The three South African variants, which were the most resistant, all shared three mutations in the receptor binding domain. This may contribute to their high resistance to neutralizing antibodies.

Currently, all approved COVID-19 vaccines work by teaching the body to produce an immune response, including antibodies, against the SARS-CoV-2 spike protein. While the ability of these variants to resist neutralizing antibodies is concerning, it doesn’t mean the vaccines won’t be effective.

“The body has other methods of immune protection besides antibodies,” says Balazs. “Our findings don’t necessarily mean that vaccines won’t prevent COVID, only that the antibody portion of the immune response may have trouble recognizing some of these new variants.”

Like all viruses, SARS-CoV-2 is expected to continue to mutate as it spreads. Understanding which mutations are most likely to allow the virus to evade vaccine-derived immunity can help researchers develop next-generation vaccines that can provide protection against new variants. It can also help researchers develop more effective preventative methods, such as broadly protective vaccines that work against a wide variety of variants, regardless of which mutations develop.


Source: Massachusetts General Hospital

More Data Suggests New Coronavirus Variants Weaken Vaccines, Treatments

There’s new evidence that fast-spreading variants of the coronavirus that causes COVID-19 are more resistant to antibody treatments and vaccines.

Researchers assessed variants first identified in South Africa, the United Kingdom and Brazil and found that they can evade antibodies that work well against the original version of the coronavirus that triggered the pandemic.

This means that the new variants — which are expected to become dominant — could reduce the effectiveness of vaccines and antibody-based drugs used to prevent or treat COVID-19, according to investigators from Washington University School of Medicine in St. Louis.

The findings are from laboratory tests of antibodies in the blood of people who’d recovered from infection with the coronavirus or were vaccinated with the Pfizer COVID-19 vaccine.

The researchers also tested antibodies in the blood of mice, hamsters and monkeys that had been vaccinated with an experimental COVID-19 vaccine that was developed at the university and can be given through the nose.

The results showed that much higher levels of antibodies are needed to neutralize the variants.

“We’re concerned that people whom we’d expect to have a protective level of antibodies because they have had COVID-19 or been vaccinated against it, might not be protected against the new variants,” said study senior author Dr. Michael Diamond, professor of medicine and of molecular microbiology and of pathology and immunology.

“There’s wide variation in how much antibody a person produces in response to vaccination or natural infection. Some people produce very high levels, and they would still likely be protected against the new, worrisome variants. But some people, especially older and immunocompromised people, may not make such high levels of antibodies,” he explained in a university news release.

“If the level of antibody needed for protection goes up tenfold, as our data indicate it does, they may not have enough. The concern is that the people who need protection the most are the ones least likely to have it,” Diamond said.

He noted that it’s not known what the consequences of the new variants will be yet.

“Antibodies are not the only measure of protection; other elements of the immune system may be able to compensate for increased resistance to antibodies. That’s going to be determined over time, epidemiologically, as we see what happens as these variants spread,” Diamond said.

“Will we see reinfections? Will we see vaccines lose efficacy and drug resistance emerge? I hope not,” he said. “But it’s clear that we will need to continually screen antibodies to make sure they’re still working as new variants arise and spread and potentially adjust our vaccine and antibody-treatment strategies.”

The study was published in the journal Nature Medicine.


Source: HealthDay

Pfizer, Moderna Both Trying for 3rd Dose Booster Shots to Combat Virus Variants

The head of US pharmaceutical company Pfizer said Tuesday the company is working on booster shots to help its vaccine protect against coronavirus variants, as mutated strains of the virus continue to spread worldwide.

US biotechnology firm Moderna said Monday it will test adding a booster of its vaccine, making it three shots in total, to help it defend against a South African variant.

“Every time a new variant comes up we should be able to test whether or not [our vaccine] is effective,” Pfizer CEO Albert Bourla told Bloomberg news. “Once we discover something that is not as effective, we will very, very quickly be able to produce a booster dose that will be a small variation to the current vaccine.”

Bourla said the coronavirus will probably not be completely eliminated, but will be reduced through pharmaceuticals to an illness like the common flu, with people getting an annual shot to defend against new strains.

Pfizer developed its vaccine with the German biotechnology company BioNTech.

Moderna said its vaccine will remain protective against the variants first identified in the UK and South Africa, although the shot appeared to be less effective against the South African strain.

Israeli officials including Prime Minister Benjamin Netanyahu have blamed the British strain for Israel’s third wave outbreak, which is raging unabated despite the successful vaccine campaign and a weeks-long nationwide lockdown.

Netanyahu issued a warning about virus mutations on Wednesday while speaking to the World Economic Forum via videoconference.

While stressing that he’s not an expert on vaccines, the prime minister said he believed “it’s just a matter of time until we hit a strain that the current vaccines are not susceptible to.”

Netanyahu said that due to mutations, “we’ll have to inoculate ourselves at least annually, that’s my guess.”

The British government’s chief scientific adviser said last week that the UK variant likely carries a higher risk of death than the original strain and that the virus is “going to be around, probably, forever.”

Israel mainly uses the Pfizer vaccine and has also received shipments of Moderna’s shot. Israel has administered a first vaccine dose to over 2.8 million of its 9.3 million citizens in its inoculation campaign and leads the world by far in vaccinations per capita.

On Wednesday the Health Ministry extended the vaccination campaign to anyone over the age of 35.

In an apparent world first, on Tuesday the Health Ministry issued a directive in favor of vaccinating children under the age of 16 who are at high risk of developing serious symptoms if they contract COVID-19. The decision is still awaiting final approval.

The death rate, test positivity rate, number of infections and number of serious cases have remained alarmingly high in Israel for weeks. Over 25 percent of the 4,605 Israelis who have died of COVID-19 succumbed to the disease in the past month alone.

In addition to the widespread British variant, the Health Ministry said Thursday it had found a total of 30 cases of the South African mutation in Israel so far.

Israel extended its closure of Ben Gurion International Airport on Wednesday and is closing most of its land borders with Jordan and Egypt to keep out virus variants. The cabinet may extend the nationwide lockdown, Israel’s third, which is set to expire on Sunday. The extension will be decided on at a cabinet meeting on Thursday, Netanyahu said.

The government’s response to the third wave of the outbreak has been hindered by coalition infighting over enforcement of restrictions in ultra-Orthodox areas.

Some ultra-Orthodox groups have ignored the lockdown rules and responded to police enforcement with violent riots. Netanyahu’s Likud party has largely sided with its ultra-Orthodox political allies against strict enforcement of the rules, while its partner in the outgoing coalition, the Blue and White party, is pushing for stricter enforcement.


Source : The Times of Israel

Chinese Health Experts Call to Suspend Pfizer’s mRNA Vaccine for Elderly After Norwegian Deaths

Zhang Hui wrote . . . . . . . . .

Chinese health experts called on Norway and other countries to suspend the use of mRNA-based COVID-19 vaccines produced by companies such as Pfizer, especially among elderly people, due to the vaccines’ safety uncertainties following the deaths of 23 elderly Norwegian people who received the vaccine.

The new mRNA vaccine was developed in haste and had never been used on a large scale for the prevention of infectious disease, and its safety had not been confirmed for large-scale use in humans, a Chinese immunologist said.

The death incidents in Norway also proved that the mRNA COVID-19 vaccines’ efficacy was not as good as expected, experts said.

As of Thursday, Norway has reported 23 deaths in connection with vaccination.

“So far, 13 of these have been assessed. Common side effects may have contributed to a severe course in frail elderly people,” the Norwegian Medicines Agency said on its website.

All the deaths have occurred in frail, elderly patients in nursing homes. All are over 80 years old and some of them over 90, Norwegian media NRK reported.

Two COVID-19 vaccines, Comirnaty, from BioNTec/Pfizer, and Moderna, are used in Norway. The vaccines have been developed on mRNA technology and have received temporary approval in the EU, according to the agency.

Norway launched a mass vaccination campaign at the end of December, with the very oldest citizens and residents of nursing homes being offered vaccination first, including those over the age of 85.

The Norwegian Medicines Agency admitted that the studies that form the basis for the temporary approval of the vaccine included very few people over the age of 85, and there is little known about how any side effects will affect these age brackets, but it said, “we assume that the side effects will largely be the same in the elderly as in those over 65 years of age.”

Chinese experts said the death incident should be assessed cautiously to understand whether the death was caused by vaccines or other preexisting conditions of these individuals.

Yang Zhanqiu, a virologist from Wuhan University, told the Global Times on Friday that the death incident, if proven to be caused by the vaccines, showed that the effect of the Pfizer vaccine and other mRNA vaccines is not as good as expected, as the main purpose of mRNA vaccines is to heal patients.

The mRNA vaccines teach human cells to make a protein to trigger an immune response; then, the immune response can protect people from getting infected if the real virus enters the body.

Meanwhile, toxic substances may be developed throughout the process of mRNA vaccinations; thus, the safety of vaccines cannot be fully ensured, Yang said.

But that’s not the case for inactivated vaccines in China, which have more mature technology, Yang said.

A Beijing-based immunologist, who requested anonymity, told the Global Times on Friday that the world should suspend the use of the mRNA COVID-19 vaccine represented by Pfizer, as this new technology has not proven safety in large-scale use or in preventing any infectious diseases.

Older people, especially those over 80, should not be recommended to receive any COVID-19 vaccine, he said.

He said that people over 80 years old have a weaker immune system and are more prone to adverse effect; thus, they should be recommended to take medicines to improve their immune system, he said.

China has started vaccination for people aged between 18 and 59, as statistics on people aged 60 years and over and people aged 18 years and below were relatively small during clinical trials of the vaccines. Thus, we cannot fully identify the efficacy and side effects for these two groups, a Beijing-based health expert who requested to be anonymous, told the Global Times.


Source : Global Times


Read also:

RT: 13 Israelis suffer FACIAL PARALYSIS after taking Pfizer Covid jab, amid influx of reports detailing adverse effects . . . . .

Epoch Times: 55 people have died in US after receiving COVID-19 vaccines . . . . .

Bloomberg: Norway Raises Concern Over Vaccine Jabs for the Elderly . . . . .

International Study: How Many People Will Take the COVID Vaccine?

Source : YouGov

Weekly COVID-19 Vaccination by % of Population in Selected Countries

Source : Deutsche Bank

Does It Matter Which COVID-19 Vaccine You Get?

Maggie Koerth wrote . . . . . . . . .

By the end of this week, the United States could have not one, but two COVID-19 vaccines authorized for emergency use. After nine months of isolation and lockdowns and more than 300,000 deaths, it is difficult to find superlatives to fit this moment. Any I come up with feel like they still understate how fantastic the news truly is. What’s more, there are even more vaccines waiting in the wings. Within a few months, we will likely have access to vaccines by Pfizer and Moderna … and Johnson & Johnson, and Novavax, and AstraZeneca. We’re going to go from desperately wishing for a vaccine, any vaccine, to having a cornucopia of choices.

But that doesn’t necessarily mean you’re going to have much ability to choose between them. At least, not anytime soon.

While people at the tail end of the vaccination priority list will likely be able to browse a veritable vaccine buffet, anyone getting vaccinated in the next few months is probably just going to have to take what’s available. That’s going to be especially true in the immediate short term, as limited supplies begin to circulate but the biggest issue remains whether any vaccine is available — not which one you want.

This is not, however, bad news. That’s because the first two vaccines available are far more effective than anyone expected they would be, and experts say either one would be great to take. It’s also not totally unprecedented. There are multiple versions of many of the vaccines we already take. For instance, there are multiple flu vaccines available every year. What’s different is the public’s awareness of the many potential vaccine options, said Dr. Rebecca Weintraub, a professor of medicine and global health at Harvard Medical School.

Our need for all those options is also a bit different, she and other experts told me. The variety of flu shots helps serve different populations — seniors need one with a higher dosage, for example, and people who are allergic to eggs need one produced without those triggers. But, in the short term, at least, the main reason we want lots of COVID-19 vaccines is because we need the extra manufacturing capacity that provides. “If we’re going to vaccinate more than 300 million people in this country, in the end we’re going to need more than two vaccines,” said Dr. Paul Offit, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia. “You want to get on top of this as quickly as you can. You want to get back to normal as quickly as you can, so the more manufacturers the better.”

And right now, the differences between the two vaccines that will be ready soonest are basically negligible, experts told me. Both Pfizer and Moderna have short-term efficacy rates near 95 percent. Both have low rates of severe side effects — though, based on analysis of clinical trial data, Pfizer’s appear to be a little lower than Moderna’s. Pfizer was also tested on a different age range and is authorized for people as young as 16, while Moderna is only seeking authorization for those age 18 and older. But that’s about it. You won’t be able to choose if you get Pfizer or Moderna … but it also really doesn’t matter at this point, experts said. You should feel confident with either.

Eventually, we will get to the point where we know more about how different vaccines better serve this or that niche population. Maybe one turns out to provide better protection for elderly people. Maybe another produces fewer allergic reactions, like the kind that happened this week in Alaska during the Pfizer rollout. It may even turn out that one or another vaccine lasts longer and requires fewer booster shots. But that data isn’t currently available, Weintraub said, because the clinical trials weren’t designed with cross comparison of the vaccines in mind.

“The endpoints are slightly different. The study populations are slightly different. So we’re not on the same field with the same exact rules when we’re comparing these clinical trials, unfortunately,” she told me.

That lack of cross comparison matters, as does the lack of information we currently have about things like how different vaccines interact with one another. “We see now that, for example, AstraZeneca is thinking about combining their vaccine with Sputnik V, the Russian vaccine, to try and gain even greater potency and breadth of coverage,” said Dr. Warner Greene, senior investigator at Gladstone Institutes, an independent, nonprofit biomedical research center in San Francisco. But currently, it wouldn’t be a good idea to get one vaccine and then decide you want to try another, because we don’t know how the two vaccines would interact (even though it’s completely possible some of those interactions could be beneficial).

Right now, though, you would not want to get one dose of Pfizer and your second dose of Moderna, said Dr. Purvi Parikh, a professor at New York University’s Grossman School of Medicine and a co-investigator on the Pfizer vaccine trials. The two are both mRNA-based vaccines, but they’re different enough that you can’t assume they’re interchangeable without research to prove it. In fact, she told me, people who get vaccines will be getting cards to document both when they are due for their second shot — and which vaccine they should get when they go back for it.

All of this is why Weintraub says it’s critical that funding and volunteering for Phase 3 clinical trials continue, even after we have two vaccines on the market. We need to have more vaccines reach authorization than just Pfizer and Moderna, and we need to know how all the authorized vaccines compare to one another. If we ever want multiple vaccines to really mean multiple options, we have to keep learning about them. Otherwise, no matter how many vaccines we have, we won’t be able to make an informed choice between them.


Source : FiveThirtyEight

Chart of the Day: How Messenger RNA Vaccines Work

Comparing Selected Vaccine Development Throughout History

Source : Business Insider


Timeline of Vaccines in History


Read also at The College of Physicians of Philadelphia:

The History of Vaccines . . . . .