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Wednesday, December 1, 2021

New strategy for antibodies to disable viruses

 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, 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 had also 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.

nand 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."

How are the antibodies distorting the dengue virus particles?

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 is a smoother surface with peaks and valleys.

Anand noted that for dengue virus, antibodies especially prefer binding the 'peaks' known as 5-fold vertices. Once all the proteins on the 5-fold vertices have been bound, antibodies will turn to their second-favorite peaks -- the 3-fold vertices. Finally, they are left with only the 2-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 5- and 3-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 2-fold vertices, and we think it's this digging into the virus particle that causes the virus to shake and distort and ultimately become non-functional."

What is the difference between Zika and dengue?

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.

What about other viruses?

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."

Are there any potential applications of the findings?

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.


Story Source:

Materials provided by Penn State. Original written by Sara LaJeunesse. Note: Content may be edited for style and length.


Journal Reference:

  1. Xin-Xiang Lim, Bo Shu, Shuijun Zhang, Aaron W.K. Tan, Thiam-Seng Ng, Xin-Ni Lim, Valerie S.-Y. Chew, Jian Shi, Gavin R. Screaton, Shee-Mei Lok, Ganesh S. Anand. Human antibody C10 neutralizes by diminishing Zika but enhancing dengue virus dynamicsCell, 2021; DOI: 10.1016/j.cell.2021.11.009

China says Olympics will proceed as planned despite Omicron

 China expects to hold the 2022 Winter Olympics "smoothly" and on schedule, despite challenges posed by the emergence of the new Omicron coronavirus variant, foreign ministry spokesman Zhao Lijian told a regular daily briefing on Tuesday.


"I believe it will definitely pose some challenge to our efforts to prevent and control the virus, but as China has experience in preventing and controlling the coronavirus, I fully believe that China will be able to host the Winter Olympics as scheduled, smoothly and successfully," Zhao said.

Beijing is set to stage the Games from Feb. 4 to Feb. 20, without foreign spectators and with all athletes and related personnel contained in a "closed-loop" and subject to daily testing for COVID-19.

Under its "zero-COVID" policy, China has had what are among the world's strictest COVID-19 prevention measures.

UT Austin researchers say process simple to modify COVID vaccine for omicron variant

 The University of Texas at Austin researchers who helped develop the technology behind the COVID-19 vaccine say the technology created works well against different variants.

UT researchers who helped develop a key part of the vaccine are now looking into ways to protect against all forms of the coronavirus. This is coming as new fears form that the current COVID vaccines might not be effective enough against the omicron variant.

"We've been focused mainly on developing next-generation vaccines. Vaccines that have improved properties," UT Professor of Molecular Bioscience, Dr. Jason McLellan said.

Dr. McLellan is one of the UT professors who helped develop the way the COVID vaccine attacks the virus.

"We're focused on making changes to the spike protein that increase the amount of spike produced from the mRNA that increases the stability of the spike protein," McLellan said.

That means the spike protein is introduced to the body, so the immune system recognizes it and makes antibodies.

As omicron spreads, vaccine makers are now preparing for vaccine modifications if needed. McLellan said those changes could be simple.

"It's just a stretch of mRNA made up of four different nucleotides and they can just change a couple of them and then you have a new vaccine," he said.

President Joe Biden addressed the nation Monday about the omicron variant and said his team doesn't believe that additional measures will be needed, but plans are in place.

"I will also direct the FDA and CDC to use the fastest process available without cutting any corners for safety to get vaccines approved and on the market if needed," Biden said.

Top infectious disease expert Dr. Anthony Fauci remains confident that the current vaccines provide a level of protection against the new omicron variant. This is showing that UT researchers' technology is working.

"Our technology that's been incorporated into the various vaccines works well for all the different variants," McLellan said.

https://cbsaustin.com/news/local/ut-austin-researchers-say-process-simple-to-modify-covid-vaccine-for-omicron-variant

'Plausible connection' between COVID-19 vaccine and period changes

 Tens of thousands of women worldwide have reported changes in menstruation after receiving the COVID-19 vaccine, raising question marks among doctors and scientists.

Complaints have included changes to the duration and flow of their periods, and even pain, according to several surveys, but most doctors have stressed that there is just not enough evidence to directly link the jab to these changes.

Moreover, they say, the changes are short-term and there is no evidence that COVID-19 vaccination adversely affects fertility.

“We think that it is plausible there is a connection, but cannot prove this correlation,” said Dr. Itamar Netzer, an OB/GYN and medical administration specialist and a subdistrict director for Clalit Healthcare Services. “We are not much wiser” now than at the start of the vaccination campaign nearly 12 months ago.
Menstrual irregularities are a normal part of women’s lives, Netzer said. Women experience periods of irregularity throughout their fertile lifespan, sometimes brought on by bacterial or viral infections or even stress, though “most often for no reason at all.”
He said between 16% and 25% of women – normal, healthy and unvaccinated – experience irregular cycles, according to various studies. Around the same percentage reported menstrual changes as a result of COVID-19. An even smaller percentage of women expressed concern following vaccination.

EARLIER THIS month, during the live-streamed meeting of the Health Ministry’s Pandemic Response Team and members of its COVID-19 Vaccination Advisory Board, Dr. Emilia Ennis, director of the Health Ministry’s Department of Epidemiology, shared data collected by the ministry on the matter.
She noted that “all authorities in the world point out that the volume of reports that they have received on the subject is low in relation to the prevalence of such symptoms in the population regardless of the vaccine” – and that Israel is no different.

Ennis said the ministry received reports of heavy or unexpected menstrual bleeding, changes in menstrual periods and menstrual bleeding in women after menopause. According to the latest data she could provide, there had been 1,300 reports of these changes after the first dose out of two million women vaccinated and 2,000 reports after the second dose out of a million vaccinations.
“There is no way to know the prevalence [of these kinds of changes] in years past or to compare whether the prevalence is now higher, which may indicate a connection to the vaccine,” Ennis said. “Prolonged irregularity or excessive and unusual bleeding can be symptoms of other disease states, so if you experience an abnormal and prolonged phenomenon, especially if you are at risk for hypercoagulability or decreased platelets, consult your doctor.”
There are several reasons why COVID-19 vaccination could have short-term impact on a woman’s menstrual cycle, according to Israel Society of Obstetrics and Gynecology chairman Prof. Roni Maymon. He said this could include immunological influences on the hormones that drive the menstrual cycle or effects mediated by immune cells in the lining of the uterus.
In these cases, the effect would not be permanent but would disappear within two or three cycles.
The society announced in September that it would launch a comprehensive study on the subject, but two months later, according to Maymon, little progress has been made.
“First, we have to get ethical approval for the study [from the Helsinki Committee] and we have not even submitted it yet,” he said.
Maymon said that the study would be retrospective, meaning it would look at the medical records of a cohort of women.

Abroad, some studies have already been conducted or are in progress.
LAST WEEK, a paper uploaded to the health data sharing site MedRxiv – not peer-reviewed – stated that as of November 10, some 37,571 menstrual cycle changes had been reported to the United Kingdom’s Medicines and Healthcare products Regulatory Agency.
This particular study, however, only looked at 2,241 women over 18 who had at least one dose of any COVID-19 vaccine. They were asked to use a web-based form to report their age, length of normal menstrual cycle, whether they use any hormonal contraception, are breastfeeding, have ever been diagnosed with a menstrual or gynecological condition and, for each dose of the vaccine, which brand they had, on which day of their cycle they were vaccinated and details of how the timing and flow of their next period compared to what they normally experience.
The results showed that the brand of the vaccine was not associated with the period changes, meaning this phenomenon is not specific to mRNA vaccines. It also found that individuals taking hormonal contraception were more likely to experience menstrual changes after vaccination, but that vaccination timing was not directly related to the effect on the next period.
Dr. Victoria Male of the Department of Metabolism, Digestion and Reproduction at Imperial College London, who led the study, said that she has also recruited 250 women for a prospective study and that data collection from that cohort is still ongoing.
Last month, a larger survey of some 19,000 women was uploaded to MedRxiv, with more disturbing results: 42% of women with regular cycles said they bled more heavily than usual. Nearly a third experienced a longer duration of menstrual bleeding.
Moreover, among a cohort of women who do not typically menstruate, 71% were on long-acting reversible contraceptives, 39% on gender-affirming hormones, and 66% of post-menopausal women reported breakthrough bleeding.
This US study was led by researchers from Washington University in St. Louis, University of Illinois at Urbana-Champaign and Harvard University.
Netzer cautioned that the survey design used by the team asked women to “recall their experiences” and that there was no objective measurement for before and after being vaccinated.
A separate European study of about 16,000 women led researchers to conclude that “there is currently no evidence suggesting a causal relationship of menstrual disorders with Comirnaty,” the marketing name for Pfizer’s coronavirus vaccine.
REGARDING THE more than 30,000 reports of menstrual changes in the UK, the Royal College of Obstetricians and Gynecologists released the following statement by its vice president Dr. Jo Mountfield: “We understand that any changes to periods following a COVID-19 vaccine can be concerning. We want to reassure women that any changes generally revert back to normal after one or two cycles.
“There is no evidence to suggest that these temporary changes will have any impact on a person’s future fertility, or their ability to have children,” she continued. “It is important to get vaccinated as the best protection against coronavirus. This is especially important if you are planning a pregnancy, as we know unvaccinated pregnant women are more at risk of becoming seriously ill from COVID-19.”
Finally, the US National Institute of Child Health and Human Development awarded five grants totaling $1.67 million last month to agencies to explore the link between COVID-19 vaccination and menstruation changes, although this research has just started, and it is too early to report results.
The research teams are from Boston University, Harvard Medical School, Johns Hopkins University, Michigan State University, and Oregon Health and Science University. The goal of their efforts is to see if the vaccine is directly linked to menstruation changes or if these changes are coincidental. They will also look at why these changes might occur and how long they might last.
Maymon said that there have been reports of reversible menstrual disturbances with other vaccines in the past, especially with the papilloma vaccination against a family of viruses that cause skin warts.
The US study published on MedRxiv also noted the link between other vaccines and period changes, including a study going back as far as 1913 that tied the typhoid vaccine with menstrual changes. They said studies of the Hepatitis B vaccine have also indicated that menstruation could be affected.
For Jewish religious women who observe the laws of family purity, these menstruation changes could be particularly challenging. However, Maymon said that once a conclusion about the phenomenon is made, “the rabbis will discuss with us and see what needs to be done according to Jewish law.”
In the meantime, stressed Netzer, “the most important thing to say is that we do know for certain that COVID-19 vaccinations do not affect fertility or pregnancy.
“In contrast, COVID-19 is very dangerous, especially for pregnant women.”

UFT calls for more testing of adults in NYC schools

 New York City Teachers' Union is now calling for more testing of adults in school buildings.


The UFT says testing is important to keep cases down in schools, especially now with the threat of the omicron variant.

The Department of Education says they have the country's largest schools surveillance testing program for students and provide courtesy testing for all staff.

School officials say so far this year, they have only had to close three schools due to COVID-19.

Nigeria says it found first case of omicron in November

 Nigeria has detected its first case of the omicron coronavirus variant in travelers who arrived from South Africa in the past week, the country’s national public health institute said Wednesday, correcting its earlier statement that it found the variant in samples taken in October.

The Nigeria Center for Disease Control said in a second statement that it was the delta variant — not omicron as it had earlier stated — that was detected in the samples from October. It said the omicron variant was first detected in three travelers who arrived in the country in the past week.

“Samples obtained for the stipulated day two test for all travelers to Nigeria were positive for this variant in three persons with history of travel to South Africa,” Nigeria CDC director-general Dr. Ifedayo Adetifa said in the second statement.

Nigeria is the first West African country to have recorded the omicron variant since scientists in southern Africa detected and reported it and adds to a list of nearly 20 countries where the variant has been recorded, triggering travel bans across the world.

Much remains unknown about the new variant, including whether it is more contagious, as some health authorities suspect, whether it makes people more seriously ill, and if it can thwart the vaccine.

The Nigeria CDC urged the country’s states and the general public to be on alert and called for improved testing amid concerns that Nigeria’s low testing capacity might become its biggest challenge in the face of the new variant.

Testing for the virus is low in many states and even in the nation’s capital, Abuja. For instance, in parts of Kuje, a suburb of Abuja, Musa Ahmed, a public health official, told The Associated Press that no one has been tested for the virus for weeks.

The detection of the omicron variant in Africa’s most populous nation, with 206 million people, coincides with Nigeria’s new requirement that all federal government employees must be inoculated or present a negative COVID-19 test result done in the last 72 hours.

With the vaccine mandate taking effect on Wednesday, there were chaotic scenes at several offices in the nation’s capital as civil servants without a vaccination card or a negative PCR test were turned away by security agents.

Many of the workers and security agents were not wearing face masks.

“Governments should invest in promoting narratives around vaccine safety, efficacy, and the broader public health security implications of poor vaccines uptake,” Adewunmi Emoruwa, lead strategist at Gatefield, an Abuja-based consultancy. “If public servants are convinced about these issues, they are naturally more effective advocates to their constituents.”

Across Nigeria, the news of the omicron variant — which the World Health Organization has warned poses “very high” risk — has triggered concerns and renewed fears over the COVID-19 pandemic.

At the airport in Lagos, Nigeria’s largest city and economic hub, authorities insisted that travelers must wear their face masks at the counters, though not much attention is paid to many others flouting health protocols around the airport premises and in the city.

Nigeria — with 214,218 confirmed infections including nearly 3,000 deaths — has updated its travel advisory, ordering incoming international travelers to have a PCR test 48 hours before embarking on their trip to the country and two more tests, two days and seven days after arrival. Incoming international arrivals must also isolate for seven days.

Amid global concern over the omicron variant, the Nigeria CDC director-general told reporters that the country remains at alert in the face of the emerging crisis.

“We are working very hard to enhance ongoing surveillance, especially for inbound travelers, and also trying to ramp up testing (including) at the land borders,” he said.

A slew of nations moved to ban travels from many countries especially southern African nations in the aftermath of the emergence of the omicron variant. But the move has been widely condemned by many including South Africa President Cyril Ramaphosa, who is currently in Nigeria on a two-day visit.

Ghana also announced Wednesday that its scientists have detected cases of the omicron coronavirus variant in passengers who arrived in the country on Nov. 21.

The cases were detected at the Kotoka International Airport in the capital, Accra, after tests were conducted on incoming passengers, the Director General of the Ghana Health Service Patrick Kuma-Aboagye said Wednesday.

“We have not seen any omicron within the community of Ghana,” he said, according to tests in the country. But, he added, the danger is that omicron could be incubating in Ghana.

Further west on the continent, Liberia launched surveillance along its borders and placed health officers assigned there on full alert although no cases of the omicron variant have been reported there.

Liberia’s Health Minister Wilhelmina Jallah urged citizens to take preventive measures but not panic. She urged them to take advantage of the vaccination campaign.

“You cannot go to war if you are not prepared for the war,” she said. “And our preparation for this war against COVID-19 — whether it is alpha, delta or omicron — is to protect ourselves by getting at least a jab in your arm ... so we just want to raise this heightened alert.”

https://apnews.com/article/coronavirus-pandemic-science-health-nigeria-west-africa-2962094cd55c7cff53c6216ebfe9fe32

First five omicron cases detected in South Korea

 Five cases of the COVID-19 omicron variant were confirmed in South Korea on Wednesday, making it the latest to join more than 20 countries that have detected the new coronavirus strain.

South Korean officials said the cases were linked to five people who traveled to Nigeria and returned at the end of November, The Associated Press reported. The country is requiring all travelers arriving in South Korea to quarantine for 10 days and has banned travelers coming from eight nations in South Africa.

Omicron, which was first detected in South Africa at the end of last month, has now been found around the world, from Sweden to Australia. The U.S. and other countries recently enacted international travel bans to stop the spread of the worrying variant, though the World Health Organization has not yet ruled whether omicron is more transmissible or deadly than previous variants, including the dominant delta variant.

But the news comes as South Korea is grappling with a surge in coronavirus cases, with more than 5,000 reported yesterday, a record. Last month, South Korea eased its social distancing and coronavirus restrictions, a move some health care officials in the country have criticized.

South Korea has reported 452,320 total cases since the pandemic began, with 3,650 total deaths. About 79 percent of the population is fully vaccinated.

https://thehill.com/homenews/coronavirus-report/583832-first-five-omicron-cases-detected-in-south-korea