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Marcus Lamb, head of Daystar, a large Christian network that discouraged vaccines, dies after getting covid-19 The Washington PostView Full Coverage on Google News
UNIVERSITY PARK, Pa. — It is widely understood that antibodies neutralize viruses by latching onto their surfaces and blocking them from infecting host cells. But new research reveals that this barrier method isn’t the only way that antibodies disable viruses. An international team of researchers led by Penn State has discovered that antibodies also distort viruses, thereby preventing them from properly attaching to and entering cells.
“Everybody thinks of antibodies as binding to viruses and blocking them from entering cells — essentially locking them down,” said Ganesh Anand, associate professor of chemistry at Penn State. “But our research reveals for the first time that antibodies may also physically distort viruses, so they are unable to properly attach to and infect host cells.”
In their study, which published online today (Nov. 30) in the journal Cell, Anand and his colleagues investigated the interactions between human monoclonal antibody (HMAb) C10 and two disease-causing viruses: Zika and dengue. The HMAb C10 antibodies they used had previously been isolated from patients infected with dengue virus and also had been shown to neutralize Zika virus.
The researchers used a combination of techniques, including cryogenic electron microscopy (cryo-EM) to visualize the viruses and hydrogen/deuterium exchange mass spectrometry (HDXMS) to understand their movement.
“Cryo-EM involves flash-freezing a solution containing molecules of interest and then targeting them with electrons to generate numerous images of individual molecules in different orientations,” explained Anand. “These images are then integrated into one snapshot of what the molecule looks like. The technique provides much more accurate pictures of molecules than other forms of microscopy.”
To document the effects of antibodies on Zika and dengue viruses, the team collected cryo-EM snapshots of the viruses under conditions of increasing concentrations of antibodies.
In parallel, the team applied HDXMS, a technique in which molecules of interest — in this case Zika and dengue virus, along with HMAb C10 antibodies — are submerged in heavy water. Heavy water, Anand explained, has had its hydrogen atoms replaced with deuterium, hydrogen’s heavier isotopic cousin.
“When you submerge a virus in heavy water, the hydrogen atoms on the surface of the virus exchange with deuterium,” he said. “You can then use mass spectrometry to measure the heaviness of the virus as a function of this deuterium exchange. By doing this, we observed that dengue virus, but not Zika virus, became heavier with deuterium as more antibodies were added to the solution. This suggests that for dengue virus, the antibodies are distorting the virus and allowing more deuterium to get in. It’s as if the virus is getting squished and more surface area becomes exposed where hydrogen can be exchanged for deuterium.”
In contrast, Zika virus did not become heavier when placed in heavy water, suggesting that its surface, while fully occupied by antibodies, is not distorted by the antibodies.
Anand explained that by combining cryo-EM and HDXMS, the team was able to get a comprehensive picture of what happens when antibodies attach to Zika and dengue viruses.
“It’s like those cartoon flipbooks, where each page has a slightly different image, and when you flip through the book, you see a short movie,” he said. “Imagine a flipbook with drawings of a racehorse. Cryo-EM shows you what the racehorse looks like and HDXMS shows you how fast the racehorse is moving. You need both techniques to be able to describe a racehorse in motion. This complementary set of tools enabled us to understand how one type of antibody differentially affects two types of viruses.”
He noted that the fact that the more antibodies they added, the more distorted the dengue virus particles became, suggests that stoichiometry — the relationship between the quantities of the reactants and the products before, during and after a chemical reaction — matters.
“It’s not enough to just have antibodies present,” he said. “How much antibody you add determines the extent of neutralization.”
In fact, the team found that at saturating conditions, in which antibodies were added at high enough concentrations to fill all the available binding locations on the dengue viruses, 60% of the virus’ surfaces became distorted. This distortion was enough to protect the cells from infection.
“If you have enough antibodies, they will distort the virus particle enough so that it’s preemptively destabilized before it even reaches its target cells,” Anand said.
Indeed, when the scientists incubated the antibody-bound dengue viruses with BHK-21 cells, a cell line from the kidneys of baby hamsters that is often used in viral infection research, they found that 50%-70% fewer cells were infected.
Anand explained that with some viruses, including Zika, antibodies work by jamming the exits so the passenger cannot get out of the car.
“We have found a new mechanism in dengue virus whereby antibodies basically total the car so it cannot even travel to a cell,” he said.
Anand explained that contrary to the now-familiar SARS-CoV-2, which has spike proteins protruding in all directions, the surfaces of both Zika and dengue are smoother with peaks and valleys.
Anand noted that for dengue virus, antibodies especially prefer binding the ‘peaks’ known as five-fold vertices. Once all the proteins on the five-fold vertices have been bound, antibodies will turn to their second-favorite peaks — the three-fold vertices. Finally, they are left with only the two-fold vertices.
“Antibodies do not like two-fold vertices because they are very mobile and difficult to bind to,” said Anand. “We found that once the five- and three-fold vertices have been fully bound with antibodies, if we add more antibodies to the solution, the virus starts to shudder. There’s this competition taking place between antibodies trying to get in and the virus trying to shake them off. As a result, these antibodies end up burrowing into the virus rather than binding onto the two-fold vertices, and we think it’s this digging into the virus particle that causes the virus to shake and distort and ultimately become nonfunctional.”
Anand explained that Zika is a much more stable, less dynamic virus than dengue, which has a lot of moving parts.
“Dengue and Zika look similar but each one has a different give. Dengue may have evolved as a more mobile virus as a way of avoiding being caught by antibodies. Its moving parts confuse and throw off the immune system. Unfortunately for dengue, antibodies have evolved a way around this by burrowing into the virus and distorting it.”
It appears, he said, that the same type of antibody can neutralize Zika and dengue in two different ways — one where it binds to the virus and deactivates it, which is the traditional way we think about antibody activity, and the other where it burrows in and distorts the virus.
Anand said the distortion strategy his team discovered may be used by antibodies when they are confronted with other types of viruses as well.
“Dengue is just a model virus that we used in our experiments, but we think this preemptive destabilization strategy may be broadly applicable to any virus,” he said. “It may be that the antibodies first attempt to neutralize viruses through the barrier method and if they are unsuccessful, they resort to the distortion method.”
The findings could be useful in designing therapeutic antibodies, Anand said.
“HMAb C10 antibodies are specific to dengue and Zika viruses, and happen to be capable of neutralizing Zika and dengue viruses in two different ways,” he said. “But you could potentially design therapeutics with the same capabilities for treating other diseases, such as COVID-19. By creating a therapeutic with antibodies that can both block and distort viruses, we can possibly achieve greater neutralization.”
He added, “You don’t want to wait for a virus to reach its target tissue, so if you can introduce such a therapeutic cocktail as a nasal spray where the virus first enters the body, you can prevent it from even entering the system. By doing this, you may even be able to use less antibody since our research shows that it takes less antibody to neutralize a virus through the distortion method. You can get better bang for the buck.”
Overall, Anand stressed that the importance of the study is that it reveals an entirely new strategy that some antibodies use to disable some viruses.
“Previously, all we knew about antibodies was that they bind and neutralize viruses,” he said. “Now we know that antibodies can neutralize viruses in at least two different ways, and perhaps even more. This research opens the door to a whole new avenue of exploration.”
Other authors on the paper include Xin-Xiang Lim, graduate student; Jian Shi, manager, Cryo-EM Facility; and Shee-Mei Lok, professor, National University of Singapore. Co-authors also include Bo Shu, research fellow; Shuijun Zhang, assistant professor; Aaron W.K. Tan, graduate student; Thiam-Seng Ng, graduate student; Xin-Ni Lim, graduate student; and Valerie Chew, assistant professor, Duke-National University of Singapore Medical School. Gavin R. Screaton, head of the Medical Sciences Division, Oxford University, also is an author.
This research was supported by the National Research Foundation of Singapore, the Ministry of Health of Singapore, and by Penn State.
The UFT says testing is important to keep cases down in schools, especially now with the threat of the omicron variant.
School officials say so far this year, they have only had to close three schools due to COVID-19.
Some NY hospitals near capacity
Five hospitals in NYC and Long Island have less than 10% capacity remaining and could have elective surgeries cancelled as soon as Friday. Two are in New York City: Long Island Jewish Forest Hills and Queens Hospital Center, both in Queens. There are three on Long Island: Long Island Community Hospital and Southside Hospital in Suffolk County and North Shore University Hospital in Nassau County. The five are on a state list that currently shows 37 hospitals in the state at 10% capacity or less. Under an executive order signed by Governor Hochul last week, any hospital with 10% or less capacity by Friday will need to shut down most elective surgeries until Jan. 15, 2022.
Pfizer to request FDA authorization for boosters for older teens
Pfizer will soon request FDA authorization to expand its booster shots to 16 and 17-year-olds. It's already approved for adults age 18 and older. Pfizer vaccines were authorized for adolescents in May, so some are nearing their six-month mark. The drug maker is also studying the omicron variant. Pfizer's CEO says the company is prepared to develop a new vaccine if necessary.
FDA endorses Merck COVID pill, paving way for US authorization of 1st at-home drug for virus
A panel of U.S. health advisers on Tuesday narrowly backed the benefits of a closely watched COVID-19 pill from Merck, setting the stage for a likely authorization of the first drug that Americans could take at home to treat the virus.
A Food and Drug Administration panel voted 13-10 that the drug's benefits outweigh its risks, including potential birth defects if used during pregnancy.
Health experts say omicron variant is result of COVID-19 vaccine inequity
The emergence of the new omicron variant and the world's desperate and likely futile attempts to keep it at bay are reminders of what scientists have warned for months: The coronavirus will thrive as long as vast parts of the world lack vaccines.
The hoarding of limited COVID-19 shots by rich countries - creating virtual vaccine deserts in many poorer ones - doesn't just mean risk for the parts of the world seeing shortages; it threatens the entire globe.
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Right now, only 16% percent of NYC school kids age 5 to 11 have gotten their first shot, and officials want to dramatically boost those numbers.
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The US Centers for Disease Control and Prevention strengthened recommendations for booster doses of coronavirus vaccine Monday, saying all adults should get boosted six months after the second dose of Pfizer/BioNTech's or Moderna's vaccine or two months after the single dose Johnson & Johnson vaccine.
It's a slight but significant tweak to the wording of guidance issued earlier this month when the CDC endorsed an expanded emergency use authorization for boosters from the US Food and Drug Administration.
New Jersey's positivity rate spikes
Gov. Phil Murphy said New Jersey's positivity rate spiked up to 9.23%, which he attributed to more testing over the Thanksgiving holiday.
"The positivity rate which has been running weekdays 4% or 5%, spiked up on Thanksgiving, the assumption I would have is you are not getting tested on Thanksgiving if you are not more than likely having symptoms," Murphy said. "The big test is over the next couple weeks to see if we will see the anticipated spike coming out of the Thanksgiving holiday, Hanukkah or the holidays to come."
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So far there have been no cases of the COVID omicron variant identified in New York City, but "it is very likely there will be," Mayor Bill de Blasio said Monday. City health officials remain in close contact with the CDC, the mayor said, and vaccinations will remain a key part of the city's strategy moving forward. Mayor-elect Eric Adams said his administration will be "on the same playbook" requiring vaccinations. "We must get vaccinated in a real way," he said. In addition, the city's health department is recommending masks now be worn at all times in indoor public settings, regardless of vaccination status.
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LeBron James has been placed in the NBA's health and safety protocols, and was ruled out for the Los Angeles Lakers' game against the Sacramento Kings on Tuesday night.
Such a move almost certainly means one of two things: that James, who said earlier this season that he is vaccinated, either tested positive for Covid-19 or had an inconclusive result.
A person with knowledge of the situation said the Lakers are preparing for James to miss multiple games. The person spoke on condition of anonymity to The Associated Press because neither the team nor James had revealed that detail publicly. ESPN previously reported that James is "expected" to miss several games.
If James tested positive, he would likely be looking at a minimum of 10 days away from the Lakers unless he returns two negative PCR tests in a 24-hour span. The Lakers learned of James' situation Tuesday morning, coach Frank Vogel said, and arranged for transportation to take him back to Los Angeles from Sacramento.
Vogel would not say if James was exhibiting any symptoms.
"Obviously it's a huge loss," Vogel said before Tuesday's game. "It's disappointing. We just want the best for him now. That's where our thoughts are."
The news that James is missing time came on the same day the NBA underscored its previous recommendation, echoed by the National Basketball Players Association, that coaches and players who are vaccinated receive a booster shot as soon as possible.
The NBA, in a memo obtained by The AP, also told its teams Tuesday that it has documented 34 cases in which a fully vaccinated player, coach or staffer had a breakthrough case of Covid-19. The league has said about 97% of players are fully vaccinated, with Brooklyn's Kyrie Irving — who has not played this season because of his status — among the exceptions.
Other NBA stars have already missed multiple games this season after testing positive, including Philadelphia's Joel Embiid — who just missed three weeks while dealing with the virus.
Tuesday's game marks James' 12th absence in the Lakers' first 23 games this season. He missed 10 games because of injuries and another because of the first NBA suspension of his 19-year career.
With James, the Lakers have gone 7-4. Without him, they were 4-7 entering Tuesday.
"We're different now than we were three weeks ago or when that first time he went out was," Vogel said. "Hopefully we'll have more success this time around."
James is averaging 25.8 points, 5.2 rebounds and 6.8 assists this season. If he is out for 10 days, he would miss at least four games.
James is the 17th player known to have entered the league's health and safety protocols since the start of the regular season. That doesn't include some players who missed time during training camp and the preseason.
"I think everyone has their own choice to do what they feel is right for themselves and their family and things of that nature," James said in September, when asked about his vaccination status. "I know that I was very (skeptical) about it all. But after doing my research and things of that nature, I felt like it was best suited for not only me but for my family and my friends. And, you know, that's why I decided to do it."
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WASHINGTON, Nov 30 (Reuters) - The U.S. is moving to require that all air travelers entering the country show a negative COVID-19 test performed within one day of departure in response to concerns about a new coronavirus variant, the Centers for Disease Control and Prevention (CDC) said late on Tuesday.
Currently, vaccinated international air travelers can present a negative test result obtained within three days from their point of departure. Nearly all foreign nationals must be vaccinated to enter the United States. Unvaccinated travelers currently must get a negative COVID-19 test within one day of arrival.
The new one-day testing requirement would apply equally to U.S. citizens as well as foreign nationals.
Reuters reported earlier that a draft proposal was circulating among government agencies for the stricter testing requirement.
A CDC spokeswoman confirmed the agency is working to modify its global testing rules for travel "as we learn more about the Omicron variant; a revised order would shorten the timeline for required testing for all international air travelers to one day before departure to the United States."
The administration is also considering whether to require air travelers to get another COVID-19 test within three to five days after arrival in the United States, officials said.
A general view of the U.S. Centers for Disease Control and Prevention (CDC) headquarters in Atlanta, Georgia September 30, 2014. REUTERS/Tami Chappell
The CDC did not confirm that, but noted it continues to recommend all "travelers should get a COVID-19 viral test 3-5 days after arrival" and "post-travel quarantine for any unvaccinated travelers."
The stricter rules could be announced Thursday, but it was not clear when they might take effect.
CDC Director Rochelle Walensky said the agency "is evaluating how to make international travel as safe as possible, including pre-departure testing closer to the time of flight and considerations around additional post-arrival testing and self-quarantines."
On Monday, the White House barred nearly all foreign nationals who have recently been in South Africa and seven other southern African countries over concerns about the Omicron variant.
A White House official said earlier Tuesday the administration is evaluating COVID-19 measures "including considering more stringent testing requirements for international travel."
On Tuesday, the CDC advised Americans against travel to Niger, Papua New Guinea, Poland, and Trinidad and Tobago, citing COVID-19 concerns.
The CDC now lists about 80 foreign destinations as having "Level Four," its highest level of COVID-19 transmission, and discourages Americans from traveling to those destinations.
Reporting by David Shepardson; editing by Sandra Maler, Cynthia Osterman and Leslie Adler
Our Standards: The Thomson Reuters Trust Principles.
Enlarge / A baby with measles. CDC The Centers for Disease Control and Prevention is putting clinicians on alert about the growing r...
