Russia says its Sputnik V COVID-19 vaccine is 92% effective

By Polina Ivanova

MOSCOW (Reuters) - Russia’s Sputnik V vaccine is 92% effective at protecting people from COVID-19 according to interim trial results, the country’s sovereign wealth fund said on Wednesday, as Moscow rushes to keep pace with Western drugmakers in the race for a shot.


FILE PHOTO: A nurse prepares Russia's "Sputnik-V" vaccine against the coronavirus disease (COVID-19) for inoculation at a clinic in Tver, Russia October 12, 2020. REUTERS/Tatyana Makeyeva

The initial results are only the second to be published from a late-stage human trial in the global effort to produce vaccines that could halt a pandemic that has killed more than 1.2 million people and ravaged the world economy.

The results are based on data from the first 16,000 trial participants to receive both shots of the two-dose vaccine, the Russian Direct Investment Fund (RDIF), which has been backing its development and marketing it globally, said.

“We are showing, based on the data, that we have a very effective vaccine,” said RDIF head Kirill Dmitriev, adding that it was the sort of news that the vaccine’s developers would talk about one day with their grandchildren.

The analysis was conducted after 20 participants in the trial developed COVID-19 and examined how many had received the vaccine versus a placebo.

That is significantly lower than the 94 infections in the trial of a vaccine being developed by Pfizer Inc PFE.N and BioNTech BNTX.O. To confirm the efficacy rate, Pfizer said it would continue its trial until there were 164 COVID-19 cases.

RDIF said the Russian trial would continue for six more months and data from the study will also be published in a leading international medical journal following a peer review.

European stocks and U.S. stock futures extended their gains slightly after Russia’s announcement.

ANOTHER BOOST

Russia’s announcement follows swiftly on from results posted on Monday by Pfizer and BioNTech, which said their shot was also more than 90% effective.

The Russian results are another boost to other COVID-19 vaccines currently in development and are a proof of concept that the disease can be halted with vaccination.

Experts said knowledge about the trial’s design and protocol was sparse, making it difficult to interpret the figures released on Wednesday.

Scientists have raised concerns about the speed at which Moscow has worked, giving regulatory go ahead for the shot and launching a mass vaccination programme before full trials to test its safety and efficacy had been completed.

Russia registered its COVID-19 vaccine for public use in August, the first country to do so, though the approval came before the start of the large-scale trial in September.

The so-called Phase III trial of the shot developed by the Gamaleya Institute is taking place in 29 clinics across Moscow and will involve 40,000 volunteers in total, with a quarter receiving a placebo shot.

The chances of contracting COVID-19 were 92% lower among people vaccinated with Sputnik V than those who received the placebo, the RDIF said.

That’s well above the 50% effectiveness threshold for COVID-19 vaccines set by the U.S. Food and Drug Administration.

RELATED COVERAGE
Turkey interested in producing Russia's Sputnik V vaccine: Russian health ministry


“I can see no a priori reason to disbelieve these results, but it’s so very hard to comment, because there is so little data there,” said Danny Altmann, a professor of Immunology at Imperial College London.

He said that while the Russian release was similar in its level of detail to the one from Pfizer and BioNTech, the key difference was that Pfizer’s release came against a backdrop of a wealth of published data on how the trial was designed, its protocol, and what its endpoints were.

The results of the early-stage trials were peer reviewed and published in September in The Lancet medical journal.

SPUTNIK V

The Russian drug is named Sputnik V after the Soviet-era satellite that triggered the space race, a nod to the project’s geopolitical importance for Russian President Vladimir Putin.

The vaccine is designed to trigger a response from two shots administered 21 days apart, each based on different viral vectors that normally cause the common cold: human adenoviruses Ad5 and Ad26.

The Pfizer and BioNTech vaccine uses messenger RNA (mRNA) technology and is designed to trigger an immune response without using pathogens, such as actual virus particles.

Russia is also testing a different vaccine, produced by the Vector Institute in Siberia, and is on the cusp of registering a third, Putin said on Tuesday, adding that all of the country’s vaccines were effective.

RDIF said as of Nov. 11 no serious side effects had been reported during the Sputnik V Phase III trial.

Some volunteers had short-term minor adverse events such as pain at the injection site, flu-like syndrome including fever, weakness, fatigue, and headache, it said.

MASS VACCINATIONS

Successful vaccines are seen as a crucial to restoring daily life around the world by helping end the health crisis that shuttered businesses and put millions out of work.

Russia registered the vaccine for domestic use in August, and has also inoculated 10,000 people considered at high risk of COVID-19 outside of the trial

Putin has said that Russia expects to start mass vaccinations by the end of the year.

“The publication of the interim results of the post-registration clinical trials that convincingly demonstrate Sputnik V vaccine’s efficacy gives way to mass vaccination in Russia against COVID-19 in the coming weeks,” Alexander Gintsburg, director of the Gamaleya Institute, said.

Moscow is rolling out a large network of vaccination rooms and residents who want the shot may be able to get it as early as next month if large volumes of doses are supplied by then, Deputy Mayor Anastasia Rakova said on Oct. 30.

However, production challenges remain. Earlier estimates that Russia could produce 30 million doses of the vaccine this year have since been scaled down.

Moscow aims to produce 800,000 doses this month, industry minister Denis Manturov has said, followed by 1.5 million in December. But significantly higher volumes of output per month are expected from early 2021.

Manturov cited issues with scaling up production from small to large-volume bioreactors, while Putin last month cited issues with the availability of equipment.

In late October, the vaccination of new volunteers was temporarily paused due to high demand and a shortage of doses.

Officials have said that domestic production of the vaccine will be used first to meet Russia’s needs.

RDIF, however, has also struck several international supply deals, amounting to 270 million doses in total.

It is expected that these will in large part be produced in other countries and RDIF has previously announced a deal to manufacture 300 million doses in India and an undisclosed amount of doses in Brazil, China and South Korea.

Trials have also begun in Belarus, and are on track to begin soon in the United Arab Emirates, Venezuela and India.

Russia reported 19,851 new coronavirus infections in the past 24 hours and a record high of 432 deaths. At 1,836,960, its overall case tally is the fifth largest in the world, behind the United States, India, Brazil and France.

Reporting by Polina Ivanova; Additional reporting by Kate Kelland, Ludwig Burger and Josephine Mason and Thyagaraju Adinarayan; Editing by David Clarke

After McCarrick report, pope vows to 'uproot evil' of clerical sexual abuse


By Philip Pullella

VATICAN CITY (Reuters) - Pope Francis, in his first public comment after the release of an explosive report on the Vatican’s mishandling of the case of ex-U.S. Cardinal Theodore McCarrick, on Wednesday again vowed to put an end to sexual abuse in the Church.

“Yesterday, the report about the painful case of ex-Cardinal Theodore McCarrick was published. I renew my closeness to the victims of every abuse and the commitment of the Church to uproot this evil,” Francis said at his weekly general audience.

He then closed his eyes and prayed silently.

The 450-page report said the late Pope John Paul II promoted McCarrick in 2000 despite rumours of his sexual misconduct, one of a series of failings by popes and officials who let him rise through the ranks regardless of repeated allegations against him.

The report also said that in 2008 former Pope Benedict overruled proposals from top aides that McCarrick undergo a Church investigation “to determine the truth and, if warranted, impose an ‘exemplary measure’”. He was instead given a verbal warning and told to keep a low profile.

Francis’ words also followed an independent inquiry in London on Tuesday that said the Roman Catholic Church in Britain betrayed its moral purpose over decades by protecting those who sexually abused children rather than caring for their victims.

Last week in Poland, the Vatican disciplined an elderly cardinal who was accused of sexually abusing a minor, the latest of several clerics to be caught up in a widening scandal in the homeland of the late Pope John Paul II.

COUNTING ON CIVIL WAR
Gun stocks tumble after upbeat vaccine news, lack of civil unrest

By Noel Randewich

(Reuters) - Shares of firearms sellers tumbled on Monday as promising data from a COVID-19 vaccine trial knocked stay-at-home stocks, and as civil unrest failed to materialize after Democrat Joe Biden emerged as the winner of last week’s presidential election.

Smith & Wesson Brands SWBI.O and rival Sturm Ruger & Co RGR.N fell more than 9%, while Vista Outdoor VSTO.N, which sells ammunition and a range of sporting goods, fell over 12%.

They were among several so-called stay-at-home stocks dropping after Pfizer PFE.N said its experimental vaccine was more than 90% effective in preventing COVID-19.

Sales of sporting goods, including hunting gear, have increased this year as consumers spend more time outdoors due to the coronavirus pandemic.

“If a vaccine that is 90% effective can truly bring COVID to an end, the return to work and school could subsequently bring sales in these categories back down to normalized levels,” Aegis Capital analyst Rommel Dionisio said in an email.

Two other big winners this year from consumers spending more time at home - Peloton Interactive PTON.O and Zoom Video Communications ZM.O - both fell more than 14%, while airlines and other companies that would benefit from an end to the health crisis rallied.

An absence of civil unrest following the election may also be hurting sentiment for gun stocks.

Worries that Joe Biden and his Democratic party would win the presidency and take control of the Senate from Republicans sent firearms sales surging in recent months, as did violent protests in several cities, and fears of new civil unrest related to Tuesday’s presidential election.

But with control of the Senate still undecided, Biden could struggle to fulfill campaign promises, including banning the sale of military style rifles.

However, Dionisio predicted that fears of gun control could still fuel another surge in firearms purchases by consumers worried they will not be able to buy them in the future.

Smith & Wesson’s shares have jumped or dropped at least 6% in every session since the election, and they are now down 11% overall since Tuesday.


Reporting by Noel Randewich; Editing by Mark Heinrich

Nearly 80% of Americans say Biden won White House, ignoring Trump's refusal to concede - Reuters/Ipsos poll

By Chris Kahn

NEW YORK (Reuters) - Nearly 80% of Americans, including more than half of Republicans, recognize President-elect Joe Biden as the winner of the Nov. 3 election after most media organizations called the race for the Democrat based on his leads in critical battleground states, according to a Reuters/Ipsos poll.

Biden - who needed 270 Electoral College votes to win - had 279 of those votes to 214 for Trump with results in three states not yet complete, according to Edison Research. In the popular vote, Biden got 76.3 million, or 50.7% of the total, to 71.6 million, or 47.6%, for Trump.

The Reuters/Ipsos national opinion survey, which ran from Saturday afternoon to Tuesday, found that 79% of U.S. adults believe Biden won the White House. Another 13% said the election has not yet been decided, 3% said Trump won and 5% said they do not know.
The results were somewhat split along party lines: about six in 10 Republicans and almost every Democrat said Biden won.

Edison Research, which conducts exit polling for Reuters and major media outlets, called the race for Biden on Saturday after he expanded his lead over Trump in Pennsylvania and appeared well on his way to amassing 270 electoral votes.

Trump has yet to recognize the result of the race. He prematurely declared victory well before the votes had been counted and has repeatedly complained without evidence that he is the victim of widespread voter fraud.

His claims have been echoed by members of Trump’s cabinet. U.S. Attorney General William Barr has authorized federal investigations of “substantial” allegations of voting irregularities, and Secretary of State Mike Pompeo on Tuesday said he foresees “a smooth transition to a second Trump administration.”

The Reuters/Ipsos poll was part of a broader survey that was conducted Friday to Tuesday and included responses before the presidential race was called.

It showed that 70% of Americans, including 83% of Democrats and 59% of Republicans, trust their local election officials to “do their job honestly.”

The poll also found that 72% think the loser of the election must concede defeat, and 60% think there will be a peaceful transition of power when Trump’s term ends in January.

The Reuters/Ipsos poll was conducted online, in English, throughout the United States. It gathered responses from 1,363 U.S. adults in all, including 469 respondents who took the poll between Saturday afternoon and Tuesday. The poll has a credibility interval, a measure of precision, of 5 percentage points.


Reporting by Chris Kahn, editing by Ross Colvin, Jonathan Oatis and Cynthia Osterman

Poll: Most Democrats And Republicans Say Biden Won (He Did)

Joe WalshForbes Staff
Business
I cover breaking news for Forbes.


TOPLINE 

An overwhelming majority of Americans from both parties believe President-elect Joe Biden won last week’s election, even though outgoing President Donald Trump and his allies are denying the outcome and attempting to fight back in court, a new poll found.

KEY FACTS

Some 79% of Americans — including around 60% of Republicans — say Biden was the rightful winner, whereas just 3% said Trump won and 13% said the election remains undecided, according to an Ipsos/Reuters poll released Tuesday.


Trump has shown no inclination to concede and congratulate Biden, but 72% of American adults believe the loser of the race ought to concede.


70% of Americans, including a majority of Democrats and Republicans, trust their local election officials to be honest, roughly matching with a pre-election YouGov poll that found 63% of voters believe state officials will count votes accurately.


The Ipsos/Reuters poll was conducted between Saturday afternoon and Tuesday, after every major news outlet projected a Biden victory.

Trump has refused to accept defeat, instead opting to spread false voter fraud allegations and press judges to overturn the election’s outcome. His campaign filed a raft of lawsuits alleging voter fraud and opaque counting processes in the week following the election, many of which were either quickly swatted down due to a lack of evidence or focused on narrow issues with little to no bearing on vote-counting. Most experts believe this pugnacious legal strategy has little chance of success, and some Trump aides reportedly see the lawsuits as an opportunity to satiate the president’s desire for a fight rather than a serious legal effort. Some Republican lawmakers have stayed loyal to Trump despite his false claims because they hope for his support in two upcoming runoff elections in Georgia, Politico reported Tuesday. But this poll could indicate many of Trump’s voters have already accepted defeat, even if Trump hasn’t.

BIG NUMBER

4. That’s how many Senate Republicans have congratulated Biden and acknowledged his victory. A far larger number of congressional Republicans have either openly endorsed Trump’s conspiracy theories about voter fraud or, like Senate Majority Leader Mitch McConnell (R-Ky.), supported Trump’s legal challenges while remaining mum about their credibility. Sen. Chris Coons (D-Del.) said Tuesday morning that some Republicans have privately accepted Biden’s win, but he did not offer any names.

Explaining the religious vote for Trump

LOUISIANA STATE UNIVERSITY

Research News

 

New research by LSU sociologists indicate it wasn't Christian nationalism that drove churchgoers' Trump vote in 2016. Rather, surprisingly, Christian nationalism was important among non-churchgoers. Christian nationalism is thought to have been an important factor in the election of Donald Trump as President of the United States in 2016--and likely drove many of his supporters to the polls in 2020. Now, new research shows Christian nationalist support of Trump isn't tied to religious institutions or attending church on a regular basis. Instead, it's tied to not attending church.

Regardless of political or personal background, voters who hold strong Christian nationalist values voted for Trump at high levels if they didn't go to church, according to 2017 survey data analyzed by Samuel Stroope and Heather Rackin, associate professors of sociology in the LSU College of Humanities & Social Sciences, with co-authors Paul Froese of Baylor University and Jack Delehanty of Clark University. The researchers define Christian nationalism as a set of beliefs about how Christianity should be prioritized in public life, in laws, and in America's national identity. In a forthcoming paper in Sociological Forum, titled "Unchurched Christian Nationalism and the 2016 U.S. Presidential Election," they call for nuance in explaining the so-called "religious vote" for Trump.

"The 2016 election may not be a straightforward story of religious communities coalescing around the Christian nationalist candidate...Christian nationalism operates differently for those inside and outside of religious institutions [and] religion's most dynamic effects on U.S. politics may have less to do with what happens inside churches than with how people--whether they are individually religious or not--use religious ideas to draw and impose boundaries around national identity," write the authors.

Stroope and Rackin pull together several threads from previous research. First, how Christian nationalism can be seen as an aspect of a larger populist ethos of victimization, embattlement, and resentment. Trump received significant support from alienated Americans who appear to be disengaged from religious congregations and other social institutions. Second, how Christian nationalist rhetoric can indicate nostalgia or be used as a veil for increasingly unpopular opinions, such as racial bias or anti-LGBTQ views. Referencing previous research, the authors write that "many Americans now feel that they are victimized for expressing traditional values concerning marriage, sexuality, and gender identity."

Detachment from religious communities can also intensify conservative attitudes.

"Institutions in general can have a stabilizing effect on people's lives and ideologies," Stroope said. "People who want to have their views 'checked' might also self-sort into institutions. Furthermore, religious communities can have a stress-buffering effect, so people feel less desperate for an authoritarian figure like Trump."

Their analysis using national data confirmed that churchgoers overall were more likely to vote for Trump than non-churchgoers. But these findings became more interesting when the researchers took Christian nationalism into account, indicated by voters' agreement or disagreement with statements such as "the federal government should declare the United States a Christian nation," or "the success of the United States is part of God's plan."

For non-churchgoers, the percentage who voted for Trump contrasted sharply. Less than 10 percent of non-churchgoers who strongly disagreed with the Christian nationalist statements voted for Trump. Meanwhile, nearly 90 percent of those who strongly agreed with Christian nationalist statements did. For regular churchgoers, however, Trump support did not have the same dramatic swing across different levels of Christian nationalist sentiment. After Stroope and Rackin controlled for an array of background characteristics, such as voters' party affiliation, the effect of Christian nationalism on Trump-voting was only clear for non-churchgoers. Stroope and Rackin did not find any evidence that Christian nationalism was tied to Trump-voting among churchgoers.

What motivated Stroope to study the religious vote for Trump in the first place was the "dissonance" he perceived between why churchgoers would vote Republican and Trump's style of Christian nationalism.

"Some of what I saw didn't quite mesh for me," Stroope said. "On the one hand, I heard anecdotal reports of patriotic church services and commentators' claims that Christian nationalism explained the 'religious vote' for Trump. Clearly, just like in other recent elections, the religious vote mattered in 2016, but I questioned whether it was because of Christian nationalism. On the other hand, research coming out of Europe on right-wing populism suggests how it seems to activate religious identity among people who aren't regular churchgoers. In some ways, Trump is actually the perfect candidate for people who aren't very religiously observant yet have Christian nationalist sentiments. He may have attracted unchurched Christian nationalist voters because he uses pro-Christian language but is himself not personally religiously observant."

So, rather than being a story of how the religious nationalist vote for Trump was driven by Christian leaders, churches, and institutions, Stroope and Rackin suggest that it was buoyed by the religiously disconnected.

"You have to keep in mind that religion is complex and multidimensional," Stroope said. "It shouldn't be surprising that many people who don't attend church still have religious beliefs and identities, and these religious identities can be used to draw boundaries, infer value, and be a salve for alienation in a changing America."

"In a relatively short time in our country, we've also seen rapid demographic and cultural change," Stroope continued. "With the first Black president in Barack Obama and marriage equality, many people see rapid changes in American society, and this can feel distressing or at least disorienting to some. And if they don't belong to a community or church where they can feel anchored and emotionally supported, their feelings of distress probably aren't soothed by things like talk radio, cable news, or social media. Likely the opposite. If they fear their identity or way of life is threatened, their distress may fester."

With religious attendance generally in decline, great uncertainty with the U.S. economy due to COVID-19 and a changing climate, Stroope and Rackin cannot dismiss the possibility of Christian nationalism becoming an even stronger driver of American politics in the future.

"There is room for yet more surprises," Rackin said.

###

A viable vaccine for tough tumors

Biomaterial-based cancer vaccine combines chemo and immunotherapy to treat triple-negative breast cancer in mice

WYSS INSTITUTE FOR BIOLOGICALLY INSPIRED ENGINEERING AT HARVARD

Research News

 

Patients with cancer have multiple treatment options available to them today, but each has its drawbacks. Chemotherapy kills rapidly dividing cancer cells, but it also damages healthy cells in the body and often does not effectively prevent tumor metastasis or disease recurrence. Immunotherapies avoid those problems by acting on a patient's immune system to generate a sustained anti-cancer response, but frequently have trouble accessing tumors due to the immunosuppressive local environment that tumors create.

Now, a new, best-of-both-worlds approach packages the cancer-killing power of chemotherapy and the long-term efficacy of immunotherapy into a biomaterial-based cancer vaccine that can be injected adjacent to a tumor site. When mice with aggressive triple-negative breast cancer (TNBC) were given the vaccine, 100% of them survived a subsequent injection of cancer cells without relapsing. This research is reported in Nature Communications.

"Triple-negative breast cancer does not stimulate strong responses from the immune system, and existing immunotherapies have failed to treat it. In our system, the immunotherapy attracts numerous immune cells to the tumor while the chemotherapy produces a large number of dead cancer cell fragments that the immune cells can pick up and use to generate an effective tumor-specific response," said co-first author Hua Wang, Ph.D., a former Postdoc and Technology Development Fellow at Harvard's Wyss Institute for Biologically Inspired Engineering and John A. Paulson School for Engineering and Applied Sciences (SEAS) who is now an Assistant Professor in the Department of Materials Science and Engineering at University of Illinois, Urbana-Champaign.

Personalized vaccines without the wait

First developed in 2009, the injectable cancer vaccine has shown great promise in treating multiple types of cancer in mice, and has been explored in clinical trials for treating melanoma at Dana Farber Cancer Institute. In the original formulation of the vaccine, molecules found in cancerous cells called tumor-associated antigens (TAAs) were incorporated together with adjuvants inside the aspirin-sized scaffold so that arriving dendritic cells could recognize them as "foreign" and mount an immune response targeted against the tumor. These TAAs can be isolated from harvested tumors or identified by sequencing the genome of cancerous cells and subsequently manufactured, but both of these processes to create personalized cancer vaccines can be long, tedious, and expensive.

"One of the critical limiting factors in the development of cancer vaccines is the selection of TAAs, because currently we only have a very small library of known antigens for a few specific tumor cell lines, and it's difficult to predict which can mount an effective immune response," said co-first author Alex Najibi, a graduate student in the lab of Wyss Core Faculty member David Mooney. "Implanting chemotherapy drugs inside the vaccine scaffold creates a burst of cancer cell death that releases TAAs directly from the tumor to the dendritic cells, bypassing the long and costly antigen development process."

Wang, Najibi, and their colleagues set out to apply this new cancer vaccine tactic to TNBC, a disease in which the tumors aggressively suppress immune activity in their local area, limiting the efficacy of immunotherapy. The team first loaded their alginate hydrogel scaffold with a protein molecule called Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF). GM-CSF stimulates the development and concentration of dendritic cells, which take up antigens from tumors and other invaders and present them to T cells in the lymph nodes and spleen to initiate an immune response. They also added the chemotherapy drug doxorubicin (Dox) attached to a peptide called iRGD. iRGD is known to penetrate tumors, and helps target the Dox to tumors upon release.

When mice with TNBC tumors were injected with the new vaccine, those that received a scaffold loaded with GM-CSF and the Dox-iRGD conjugate showed significantly better penetration of the drug into tumors, increased cancer cell death, and fewer metastatic tumors in the lungs than those that received gels containing Dox conjugated to a scrambled peptide molecule, unmodified Dox, or were untreated. Analysis of the scaffolds showed that they had accumulated a large number of dendritic cells, indicating that both the immunotherapy and chemotherapy components of the vaccine were active.

Encouraged by these results, the team then experimented with adding a third component to the vaccine called CpG, a synthetic bacterial DNA sequence that is known to enhance immune responses. Mice that received vaccines with this addition displayed significantly slower tumor growth and longer survival times than mice that received vaccines without it. To evaluate the strength and specificity of the immune response generated by this three-part vaccine, the researchers extracted and analyzed cells from the animals' lymph nodes and spleens. Strikingly, 14% of the T cells taken from lymph nodes reacted against the tumor cells, indicating that they had been "trained" by the dendritic cells to target the cancer, compared with only 5.3% of the mice that received the two-part vaccine and 2.4% of the T cells from untreated mice. In addition, giving a "booster" dose of the vaccine 12 days post-injection increased their survival time even further.

Localized action, long-term protection

While these results revealed the vaccine's effect on activating the immune system, the team also wanted to understand how it affected the local tumor microenvironment. Analysis of the vaccines and their nearby tumors revealed that cells in tumors treated with gels containing GM-CSF, Dox-iRGD, and CpG had an increased amount of the protein calreticulin on their surfaces, which is an indicator of cell death. Mice that received the three-part vaccine also displayed higher numbers of pro-inflammatory macrophages: white blood cells that are associated with improved anticancer activity and longer survival.

The researchers also discovered that their treatment caused an increase in the expression of the cell-surface protein PD-L1 on tumor cells, which is used by cancer to evade immune detection. They had a hunch that co-administering an anti-PD-1 checkpoint inhibitor treatment that blocks this immune evasion with their vaccine would increase its effectiveness. They implanted the three-part vaccine into mice, then injected anti-PD-1 separately. Mice treated with the combination of gel vaccine and anti-PD-1 showed significantly reduced tumor size and number, and survived for a median of 40 days compared to 27 days for untreated mice and 28 days for mice that received anti-PD-1 alone. This synergy suggested that the vaccine might best be used in combination with checkpoint inhibitor therapies.

To imitate how the cancer vaccine might be administered to human patients, the team tested its ability to prevent cancer recurrence after a primary tumor is removed. They surgically excised TNBC tumors from mice, then injected either their three-part hydrogel vaccine or a liquid vaccine containing all the components in a suspension near the original tumor site. Both treated groups had significantly lower tumor recurrence, but the gel vaccine produced significantly slower tumor growth and improved survival. Mice were then re-challenged with an injection of cancer cells and, strikingly, 100% of the mice that had received the gel vaccine survived with no metastasis, while all of the untreated mice succumbed to the disease.

"The ability of this vaccine to elicit potent immune responses without requiring the identification of patient-specific antigens is a major advantage, as is the ability of local chemotherapy delivery to bypass the severe side effects of systemic chemotherapy, the only treatment currently available for the disease," said corresponding author Mooney, Ph.D., who leads the Immuno-Materials platform at the Wyss Institute and is also the Robert P. Pinkas Family Professor of Bioengineering at SEAS. "Not only does this vaccine activate dendritic cells with tumor-specific TAAs in situ, it also reshapes the tumor microenvironment to allow the immune system greater access to the tumor, and creates an immune memory that prevents further recurrences."

The team is continuing to explore the combination of chemotherapy with cancer vaccines, and hopes to improve their antitumor efficacy for other difficult-to-treat tumor models. The team hopes that future studies to better understand and optimize the system will allow it to move into preclinical trials and, eventually, human patients.

"The team's newest version of their cancer vaccine is a novel multifunctional anticancer therapy that offers new hope for the treatment of a wide range of cancers. It is essentially an entirely new form of combination chemotherapy that can be administered through a single injection and potentially offer greater efficacy with much lower toxicity than conventional treatments used today," said Wyss Institute Founding Director Don Ingber, M.D., Ph.D. Ingber is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children's Hospital, as well as Professor of Bioengineering at SEAS.

###

Additional authors of the paper include Wyss and SEAS members Miguel Sobral, Bo Ri Seo, Ph.D., David Wu, D.M.D., and Catia Verbeke, Ph.D., and former members Jun Yong Lee, Ph.D., who is now an Assistant Professor at the Catholic University of Korea, and Aileen Li, Ph.D., who is now a Postdoctoral Fellow at the University of California, San Francisco.

This work was supported by the National Institutes of Health, the Wyss Technology Development Fellowship, and the National Science Foundation.

Researchers discover enzyme suppressing immune response to viral infections

Findings could lead to targeted therapy for persistent infections and other diseases

UNIVERSITY OF MISSOURI-COLUMBIA

Research News

 

Viruses such as HIV, hepatitis B and hepatitis C evade or disrupt the immune system to create persistent infections. These viruses remain a serious health threat, but researchers from the University of Missouri School of Medicine have discovered how an enzyme that regulates several cellular processes might be a key target to preventing viruses from disarming the human immune response.

"There is very little research on how the sphingosine kinase 2 (SphK2) enzyme affects the immune responses to viral infections," said senior author Bumsuk Hahm, PhD, associate professor of surgery and molecular microbiology and immunology. "We hypothesized that this enzyme suppresses the T cells that fight infections and allows viruses to persist."

Hahm and his team tested their hypothesis by infecting mice with the lymphocytic choriomeningitis virus, a common rodent-borne virus. Mice in the study that received an oral therapy that briefly inhibited the SphK2 enzyme experienced a robust immune response and an accelerated destruction of the virus.

"SphK2 is shown to regulate immune cell responses during a viral infection, and inhibition of this enzyme is effective in clearing a persistent viral infection," Hahm said. "We believe targeting SphK2 may provide a promising route for developing a drug to elicit protective immunity against viral infections that have a devastating impact on human health."

Another key finding from the study demonstrated that SphK2 plays a role in preventing the immune system from attacking the kidneys during an infection. Hahm's team found SphK2 deficient mice died within two weeks of infection from kidney failure. All showed evidence of immune cell infiltration in the kidneys.

Hahm's team also discovered SphK2 inhibition may also treat some types of cancer by promoting activation of the immune system. Other clinical trials are already exploring the idea that SphK2 inhibition can slow cancer cell growth by directly blocking cancer cell proliferation.

"Our study suggests that SphK2 can be targeted for restoring T cell immunity to circumvent an immune suppressive environment," Hahm said. "This finding may be applicable to cancer studies as well as other diseases caused by immune disruption."

###

In addition to Hahm, the study authors include current MU graduate students Caleb Studstill and Jennifer Wolf; Curtis Pritzl, PhD, from the surgery and molecular microbiology and immunology departments; Ravi Nistala, MD, associate professor of clinical medicine; and Dae Young Kim, PhD, clinical associate professor of veterinary medicine.

Their study, "Sphingosine kinase 2 restricts T cell immunopathology but permits viral persistence," was recently published in the Journal of Clinical Investigation. The authors of the study declare that they have no conflicts of interest.

Rapid test can ID unknown causes of infections throughout the body

All-in-one 'metagenomic' test advances efforts to eliminate lengthy diagnosis

UNIVERSITY OF CALIFORNIA - SAN FRANCISCO

Research News

 

UC San Francisco scientists have developed a single clinical laboratory test capable of zeroing in on the microbial miscreant afflicting patients hospitalized with serious infections in as little as six hours -- irrespective of what body fluid is sampled, the type or species of infectious agent, or whether physicians start out with any clue as to what the culprit may be.

The test will be a lifesaver, speeding appropriate drug treatment for the seriously ill, and should transform the way infectious diseases are diagnosed, said the authors of the study, published November 9, 2020 in Nature Medicine.

"The advance here is that we can detect any infection from any body fluid, without special handling or processing for each distinct body fluid," said study corresponding author Charles Chiu, MD, PhD, a professor in the UCSF Department of Laboratory Medicine and director of the UCSF-Abbott Viral Diagnostics and Discovery Center. "It's a simple procedure."

Conventional diagnostic tests are designed to detect only one or sometimes a small panel of potential pathogens. In contrast, the new protocol employs powerful "next-generation" DNA-sequencing technology to account for all DNA in a sample, which may be from any species -- human, bacterial, viral, parasitic, or fungal. Clinicians do not need to have a suspect in mind. To identify a match, the new test relies on specially developed analytical software to compare DNA sequences in the sample to massive genomic databases covering all known pathogens.

Chiu and colleagues at the UCSF Center for Next-Gen Precision Diagnostics first developed this method to identify infectious agents in spinal fluid in cases of encephalitis and meningitis, notably helping to save a long-sick boy's life, and later validating the protocol for use as a clinical test that is now being ordered by physicians at hospitals nationwide.

Chiu and collaborators also developed a similar blood test for sepsis, a leading killer of hospital patients, while other tests use respiratory fluid to diagnose infectious causes of pneumonia.

But each of these tests is designed to work only with specific body fluids, not all. Unfortunately, physicians are often uncertain of the origin of a patient's infection and must send off samples of several different body fluids simultaneously for lab analysis.

In the new study, the UCSF researchers, including Center for Next-Gen Precision Diagnostics co-founders Joe DeRisi, PhD, and Steve Miller, MD, PhD, compared performance of their new single-protocol "metagenomic" DNA test to gold-standard laboratory culture-based tests and now-standard PCR-based DNA tests, using two high-powered DNA sequencing technologies to diagnose bacterial or fungal infection. One was a portable, pocket-sized sequencer made by Oxford Nanopore Technologies, which can complete sequencing within six hours and to date has been used almost exclusively by research labs. The other was Illumina sequencing, which can simultaneously handle many samples in parallel and which already is used in some clinical labs (including at UCSF), but which requires more than 24 hours to complete.

The researchers analyzed body fluids -- 180 samples from in and around the lungs, the peritoneal cavity, pus-filled abscesses, the spinal cord, joints, and other sites such as tonsillar fluid and even vitreal (eye) fluid-- from 160 patients, 144 of whom were hospitalized.

Compared with gold-standard culture and PCR, the researchers diagnosed 79% of bacterial and 91% of fungal infections by Illumina sequencing, and 75% of bacterial and 91% of fungal infections by nanopore sequencing.

Using the metagenomic DNA test, Chiu and colleagues were also able to diagnose infections in seven of 12 patients whose illnesses had remained undiagnosed after standard culturing or PCR-based DNA testing.

"We think this one metagenomic test can potentially replace all PCR-based DNA tests now being used to detect hundreds of organisms that can't be adequately cultured," Chiu said.

The researchers are now moving towards FDA regulatory approval in hopes of making this test a standard part of clinical practice at UCSF and elsewhere.

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Scientists use bacteria as micro-3D printers

Technique creates highly customized structures that could be used in regenerative medicine

AALTO UNIVERSITY

Research News

 

IMAGE: THE NANOCELLULOSE FIBRES CREATED BY THE BACTERIA ARE ABOUT A THOUSAND TIMES THINNER THAN THE WIDTH OF A HUMAN HAIR. view more 

CREDIT: IMAGE: LUIZ GRECA

A team at Aalto University has used bacteria to produce intricately designed three-dimensional objects made of nanocellulose. With their technique, the researchers are able to guide the growth of bacterial colonies through the use of strongly water repellent - or superhydrophobic - surfaces. The objects show tremendous potential for medical use, including supporting tissue regeneration or as scaffolds to replace damaged organs. The results have been published in the journal ACS Nano.

Unlike fibrous objects made through current 3D printing methods, the new technique allows fibres, with a diameter a thousand times thinner than a human hair, to be aligned in any orientation, even across layers, and various gradients of thickness and topography, opening up new possibilities for application in tissue regeneration. These kinds of physical characteristics are crucial for support materials in the growth and regeneration of certain types of tissues found in muscles as well as in the brain.

'It's like having billions of tiny 3D printers that fit inside a bottle,' explains Luiz Greca, a doctoral student at Aalto University. 'We can think of the bacteria as natural microrobots that take the building blocks provided to them and, with the right input, create complex shapes and structures.'

Once in a superhydrophobic mould with water and nutrients --sugar, proteins and air -- the aerobic bacteria produce nanocellulose. The superhydrophobic surface essentially traps a thin layer of air, which invites the bacteria to create a fibrous biofilm replicating the surface and shape of the mould. With time, the biofilm grows thicker and the objects become stronger.

Using the technique, the team has created 3D objects with pre-designed features, measuring from one-tenth the diameter of a single hair all the way up to 15-20 centimetres. The nano-sized fibres do not cause adverse reactions when placed in contact to human tissues. The method could also be used to grow realistic models of organs for training surgeons or improving the accuracy of in-vitro testing.

'It's really exciting to expand this area of biofabrication that takes advantage of strong cellulose nanofibres and the networks they form. We're exploring applications for age-related tissue degeneration, with this method being a step forward in this and other directions,' says research group leader Professor Orlando Rojas. He adds that the strain of bacteria used by the team, Komagataeibacter medellinensis, was discovered in a local market in the city of Medellin, Colombia, by previous collaborators from Universidad Pontificia Bolivariana. In both nature and engineering, superhydrophobic surfaces are designed to minimise the adhesion of dust particles as well as microorganisms. This work is expected to open new possibilities for using superhydrophobic surfaces to precisely produce naturally manufactured materials.

As the bacteria can be removed or left in the final material, the 3D objects can also evolve as a living organism over time. The findings provide an important step towards harnessing full control over bacterially fabricated materials.

'Our research really shows the need to understand both the fine details of bacteria interaction at interfaces and their ability to make sustainable materials. We hope that these results will also inspire scientists working on both bacteria-repelling surfaces and those making materials from bacteria,' says Dr. Blaise Tardy.

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E-cigarettes can be 'gateway' to cigarettes for teens with no prior intention to smoke

CHILDREN'S NATIONAL HOSPITAL

Research News

 

Cigarette smoking remains a leading preventable cause of morbidity and mortality in the United States. And while adolescent cigarette smoking has declined over the past several decades, e-cigarette use presents a new risk for nicotine use disorder. a new study, published Nov. 9 in the journal Pediatrics, finds that e-cigarette use is associated with a higher risk of cigarette smoking among adolescents who had no prior intention of taking up conventional smoking. These findings have strong implications for practice and policy, researches say.

"Research is showing us that adolescent e-cigarette users who progress to cigarette smoking are not simply those who would have ended up smoking cigarette anyway," says Olusegun Owotomo, M.D., Ph.D., M.P.H., the study's lead author and a pediatric resident at Children's National Hospital. "Our study shows that e-cigarettes can predispose adolescents to cigarette smoking, even when they have no prior intentions to do so."

In one of the first theory-guided nationally representative studies to identify which adolescent e-cigarette users are at most risk of progressing to cigarette smoking, Researchers looked at data of more than 8,000 U.S. adolescents, ages 12-17, who had never smoked. The data was collected by the Population Assessment of Tobacco and Health (PATH) study, an NIH and FDA collaborative nationally representative prospective cohort study of tobacco use, from 2014-2016. Among adolescents who did not intend to smoke cigarettes in the future, those who used e-cigarettes were more than four times more likely to start smoking cigarettes one year later compared to those who did not use e-cigarettes.

E-cigarette use constitutes a relatively new risk factor for nicotine use disorder among U.S. adolescents. A 2019 study from the Centers for Diseases Control and Prevention found that 28% of high school students and 11% of middle school students were current e-cigarette users. With the recent emergence of newer and potentially highly addictive e-cigarette products, adolescents who use e-cigarettes are at increased risk of developing nicotine use disorder and progressing to smoke conventional cigarettes.

"Abstinence from e-cigarettes can protect teens from becoming future smokers and should be framed as a smoking prevention strategy by all concerned stakeholders," says Dr. Owotomo. "Pediatricians are best positioned to educate patients and families on the clinical and psychosocial consequences of e-cigarette use and should support education campaigns and advocacy efforts geared to discourage adolescent e-cigarette use."

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