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To: Winfastorlose who wrote (1305897)6/29/2021 12:57:17 PM
From: pocotrader  Read Replies (1) | Respond to of 1578472
 
How Immunity Generated from COVID-19 Vaccines Differs from an Infection
Posted on June 22nd, 2021 by Dr. Francis Collins

A key issue as we move closer to ending the pandemic is determining more precisely how long people exposed to SARS-CoV-2, the COVID-19 virus, will make neutralizing antibodies against this dangerous coronavirus. Finding the answer is also potentially complicated with new SARS-CoV-2 “variants of concern” appearing around the world that could find ways to evade acquired immunity, increasing the chances of new outbreaks.

Now, a new NIH-supported study shows that the answer to this question will vary based on how an individual’s antibodies against SARS-CoV-2 were generated: over the course of a naturally acquired infection or from a COVID-19 vaccine. The new evidence shows that protective antibodies generated in response to an mRNA vaccine will target a broader range of SARS-CoV-2 variants carrying “single letter” changes in a key portion of their spike protein compared to antibodies acquired from an infection.

These results add to evidence that people with acquired immunity may have differing levels of protection to emerging SARS-CoV-2 variants. More importantly, the data provide further documentation that those who’ve had and recovered from a COVID-19 infection still stand to benefit from getting vaccinated.

These latest findings come from Jesse Bloom, Allison Greaney, and their team at Fred Hutchinson Cancer Research Center, Seattle. In an earlier study, this same team focused on the receptor binding domain (RBD), a key region of the spike protein that studs SARS-CoV-2’s outer surface. This RBD is especially important because the virus uses this part of its spike protein to anchor to another protein called ACE2 on human cells before infecting them. That makes RBD a prime target for both naturally acquired antibodies and those generated by vaccines. Using a method called deep mutational scanning, the Seattle group’s previous study mapped out all possible mutations in the RBD that would change the ability of the virus to bind ACE2 and/or for RBD-directed antibodies to strike their targets.

In their new study, published in the journal Science Translational Medicine, Bloom, Greaney, and colleagues looked again to the thousands of possible RBD variants to understand how antibodies might be expected to hit their targets there [1]. This time, they wanted to explore any differences between RBD-directed antibodies based on how they were acquired.

Again, they turned to deep mutational scanning. First, they created libraries of all 3,800 possible RBD single amino acid mutants and exposed the libraries to samples taken from vaccinated individuals and unvaccinated individuals who’d been previously infected. All vaccinated individuals had received two doses of the Moderna mRNA vaccine. This vaccine works by prompting a person’s cells to produce the spike protein, thereby launching an immune response and the production of antibodies.

By closely examining the results, the researchers uncovered important differences between acquired immunity in people who’d been vaccinated and unvaccinated people who’d been previously infected with SARS-CoV-2. Specifically, antibodies elicited by the mRNA vaccine were more focused to the RBD compared to antibodies elicited by an infection, which more often targeted other portions of the spike protein. Importantly, the vaccine-elicited antibodies targeted a broader range of places on the RBD than those elicited by natural infection.

These findings suggest that natural immunity and vaccine-generated immunity to SARS-CoV-2 will differ in how they recognize new viral variants. What’s more, antibodies acquired with the help of a vaccine may be more likely to target new SARS-CoV-2 variants potently, even when the variants carry new mutations in the RBD.

It’s not entirely clear why these differences in vaccine- and infection-elicited antibody responses exist. In both cases, RBD-directed antibodies are acquired from the immune system’s recognition and response to viral spike proteins. The Seattle team suggests these differences may arise because the vaccine presents the viral protein in slightly different conformations.

Also, it’s possible that mRNA delivery may change the way antigens are presented to the immune system, leading to differences in the antibodies that get produced. A third difference is that natural infection only exposes the body to the virus in the respiratory tract (unless the illness is very severe), while the vaccine is delivered to muscle, where the immune system may have an even better chance of seeing it and responding vigorously.

Whatever the underlying reasons turn out to be, it’s important to consider that humans are routinely infected and re-infected with other common coronaviruses, which are responsible for the common cold. It’s not at all unusual to catch a cold from seasonal coronaviruses year after year. That’s at least in part because those viruses tend to evolve to escape acquired immunity, much as SARS-CoV-2 is now in the process of doing.

The good news so far is that, unlike the situation for the common cold, we have now developed multiple COVID-19 vaccines. The evidence continues to suggest that acquired immunity from vaccines still offers substantial protection against the new variants now circulating around the globe.

The hope is that acquired immunity from the vaccines will indeed produce long-lasting protection against SARS-CoV-2 and bring an end to the pandemic. These new findings point encouragingly in that direction. They also serve as an important reminder to roll up your sleeve for the vaccine if you haven’t already done so, whether or not you’ve had COVID-19. Our best hope of winning this contest with the virus is to get as many people immunized now as possible. That will save lives, and reduce the likelihood of even more variants appearing that might evade protection from the current vaccines.

Reference:

[1] Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection. Greaney AJ, Loes AN, Gentles LE, Crawford KHD, Starr TN, Malone KD, Chu HY, Bloom JD. Sci Transl Med. 2021 Jun 8.

Links:

COVID-19 Research (NIH)

Bloom Lab (Fred Hutchinson Cancer Research Center, Seattle)

NIH Support: National Institute of Allergy and Infectious Diseases




To: Winfastorlose who wrote (1305897)6/29/2021 1:21:28 PM
From: pocotrader  Read Replies (1) | Respond to of 1578472
 
How Dangerous Is the Delta Variant, and Will It Cause a COVID Surge in the U.S.? A new, more transmissible form of SARS-CoV-2 is rapidly spreading in the country and poses a threat to unvaccinated and partially vaccinated people

The Delta variant is here. First identified in India, this more transmissible form of the novel coronavirus has spread to at least 77 countries and regions and now makes up more than 20 percent of all U.S. cases. The Centers for Disease Control and Prevention has identified it as a “ variant of concern.” If vaccination rates fail to keep pace with its spread, experts say, the variant could lead to new COVID surges in parts of the country where a substantial proportion of the population remains unvaccinated.

Studies to date suggest the Delta variant is between 40 and 60 percent more transmissible than the Alpha variant first identified in the U.K.—which was already 50 percent more transmissible than the original viral strain first detected in Wuhan, China. Delta has quickly become the dominant variant in the U.K. and has led to another surge in cases there, despite the population’s high vaccination rate. And it is rapidly becoming more prevalent in the U.S. A preprint study, which has not yet been peer-reviewed, found that Delta and another variant called Gamma, first identified in Brazil, are rapidly replacing Alpha, which had previously been the most common U.S. variant. If current trends continue, Delta will likely become the country’s dominant variant in a few weeks, according to William Lee, vice president of science at the genomics company Helix, who co-authored the study.

“It is the most hypertransmissible, contagious version of the virus we’ve seen to date, for sure—it’s a superspreader strain if there ever was one,” says Eric Topol, a professor of molecular medicine and an executive vice president at the Scripps Research Institution. The U.S. is poorly prepared, he says. Less than half of the nation’s population is fully vaccinated—and that number is much lower in some states, particularly in the South and Mountain West. “We’ve been warned three times by the U.K.,” Topol says, referring to previous surges in early 2020 and last winter. “This time is the third warning.”

There is some indication that the Delta variant may also result in more severe disease. A study in Scotland, published in the Lancet, found the hospitalization rate of patients with that variant was about 85 percent higher than that of people with the Alpha variant. But because of the time lag between hospitalizations and deaths, there is not enough data to say whether or not Delta is more deadly than other variants. “The thing we were surprised by is just how rapidly the Delta variant took hold,” says Aziz Sheikh, a professor of primary care at the University of Edinburgh and lead author of the Lancet study. “We were again in an exponential phase of growth of cases.” This should be a lesson for the U.S., he says.

Fortunately, vaccination appears to provide good protection against Delta—although one dose seems to offer less protection than it did against other variants. A preprint study by Public Health England found that two doses of the Pfizer-BioNTech vaccine and two doses of the AstraZeneca vaccine were 96 percent and 92 percent effective, respectively, at preventing hospitalization in people infected with Delta That result is comparable to the level of protection seen against other variants. Meanwhile a single dose of the AstraZeneca vaccine was only 71 percent effective against hospitalization caused by Delta (a single dose of Pfizer was still 94 percent effective), and one shot of either vaccine was only about 33.5 percent effective against symptomatic COVID from that variant, highlighting the importance of getting both doses. The U.K., which had postponed second doses in an effort to vaccinate a larger portion of its population quickly, has now delayed its reopening plans by four weeks to allow time for more people to get both doses.

Several experts said they do not expect the Delta variant to cause a nationwide surge here in the U.S. like the one that occurred last winter. But they do anticipate localized outbreaks in places where vaccination rates remain low. “I think it really is going to depend on a community-to-community basis,” says Angela Rasmussen, a virologist at the Vaccine and Infectious Disease Organization–International Vaccine Center in Saskatchewan. The outcome will also depend on the climate and people’s behavior, she notes. In hot places where people spend a lot of time in air-conditioned buildings and vaccination rates are low—such as parts of Arizona and Texas—“I think we’ll definitely see local surges,” she says. But in San Francisco or New York City, where a large percentage of the population is fully vaccinated, she believes it will be a lot harder for the virus to gain a footing.

“We were headed down to containment for the first time in the entire pandemic in this country, and we’re going to take a detour,” Topol says. The best-case scenario, he adds, would be if Delta only causes some small and isolated bumps in cases—like the Alpha variant did in Michigan earlier this year while cases continued to decline elsewhere in the country. Within the next few weeks, the Delta variant will become dominant in the U.S., Topol says. “We’re going to likely see this patchwork phenomena,” he notes. “Certain places will light up, and hopefully they won’t light up too badly.”

Vaccination remains the best tool for combatting a Delta surge, according to Topol and others. It is unrealistic to expect that U.S. leaders will reimpose a lockdown or other restrictions, they say, so the focus should instead be on getting more people vaccinated as quickly as possible. Vaccine hesitancy and outright refusal remain major roadblocks, particularly among Republicans. Some states are offering generous incentives for vaccination, and there is some evidence that they help. Despite the widespread availability of vaccines, however, “there’s still a big problem with people not having easy access,” Rasmussen says. Some people may live far from the nearest pharmacy, or they may mistakenly believe that they have to pay for the vaccine. “We should start going door-to-door,” she says.

One group that appears to be more difficult to persuade is young adults. U.K. data indicate most of the Delta cases have been in younger people, who are less likely to have been vaccinated. In the U.S., adults aged 18 to 29 have had the lowest vaccination rates of any age age group, a recent CDC report found. Members of this group have a lower risk of severe disease or dying from COVID, but they can still be hospitalized and are at risk of developing long-haul symptoms. “There are still plenty of negative outcomes,” Rasmussen says.

Experts say the Delta variant poses a relatively low threat to fully vaccinated people. “You should not worry at all” if you have had two doses of the Pfizer-BioNTech or Moderna vaccine, Topol says. Less is known about how well the Johnson & Johnson vaccine protects against the Delta variant. And immunocompromised people still need to be somewhat careful even if they are vaccinated because they may not have developed strong immunity from the vaccine. Reports of a recent outbreak in Israel suggest that some fully vaccinated adults who had gotten the Pfizer-BioNTech vaccine were still infected, prompting the country to reimpose indoor mask mandates. But in the very rare cases where vaccinated people have gotten COVID, the data show it is much less likely to be severe. “We haven’t seen any variant that has overridden our vaccines,” Topol says.

scientificamerican.com