US hoping for two Covid-19 vaccines by end of November

Two American companies expect to apply for emergency approval for their COVID-19 vaccines by late November, welcome news as the US hits a third surge of its coronavirus epidemic and approaches its eight millionth case.

Pfizer said Friday it hopes to move ahead with its vaccine after safety data is available in the third week of November, a couple of weeks after the November 3 presidential election.

The announcement means the United States could have two vaccines ready by the end of the year, with Massachusetts biotech firm Moderna aiming for November 25 to seek authorization.

“So let me be clear, assuming positive data, Pfizer will apply for Emergency Authorization Use in the US soon after the safety milestone is achieved in the third week of November,” the company’s chairman and CEO Albert Bourla said in an open letter. The news lifted the company’s shares two percent in the US.

But experts warn that even when vaccines are approved, it will take many months until they are widely available.

In any case, they are unlikely to be a good substitute for mask wearing, social distancing and other recommended behavior to curb transmission because we don’t know how effective they will be.

Indoor gatherings in colder weather

After falling numbers throughout the summer, the country hit an inflection point in its coronavirus outbreak around the second week of September—with a new daily case average of more than 50,000 according to the latest figures, and the trajectory is upward.

With a shade under eight million confirmed infections and more than 217,000 deaths, America is the hardest-hit country in the world.

The US never came close to returning to its baseline after its first wave in spring, meaning the current spike can be more accurately termed a third surge.

Geographically, the major hotspots are in the Upper Midwest and parts of the Rocky Mountains in the west, while parts of the Northeast that were hit hard in spring are seeing their outbreaks starting to rekindle.

Harvard surgeon and health policy researcher Thomas Tsai told AFP there were multiple factors behind the rising cases—from under testing in the Midwest to authorities failing to monitor the reopening of bars and restaurants and dialing back when necessary.

What’s more, “from the contact tracing reports from various municipalities and states, the worry is that the spread is driven now, by indoor social gatherings in people’s homes,” he added, as the focus of social life shifts from public to private spaces in the colder weather.

One bright sign is that COVID-19 treatments have improved markedly, and since the cases are more spread out than before, hospitals aren’t being overwhelmed.

Widespread mask use might also mean that when people do get infected, they have less virus in their body which makes them less sick.

‘No magic bullet’

While vaccines are a crucial tool against the virus, experts have warned they can’t be a substitute for behavioral measures like masks and distancing.

“It’s welcome news that there will be one more thing that can help prevent COVID transmission,” said Priya Sampathkumar, an infectious disease doctor and professor at Mayo Clinic.

“But I think we need to be cautious and understand that a vaccine isn’t a magic bullet,” she added.

Pfizer and Moderna, both funded by the US government, launched Phase 3 of their clinical trials at the end of July, and both were producing their doses at the same time.

They aim to deliver tens of millions of doses in the US by the end of the year.

Both are “mRNA vaccines,” an experimental new platform that has never before been fully approved.

They both inject people with the genetic material necessary to grow the “spike protein” of SARS-CoV-2 inside their own cells, thus eliciting an immune response the body will remember when it encounters the real virus.

This effectively turns a person’s own body into a vaccine factory, avoiding the costly and difficult processes that more traditional vaccine production requires.

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New discovery could help improve cancer vaccines

Cancer vaccines have shown promise in treating certain tumors, such as melanoma. But such vaccines have limitations. They often target normal proteins that may be more abundant in the tumor but also are present in healthy tissue, which can lead to off-target effects that cause autoimmune disorders and also reduce the effectiveness of the vaccines.

The mutated DNA of cancer cells often produces abnormal proteins, whose fragments can help distinguish the tumor from healthy tissue. Such protein fragments could be harnessed to train the immune system to attack the tumors with, in theory, few side effects. Now, a broad collaboration of scientists in academia and industry have identified the most important features of the protein fragments to help researchers design better immunotherapies against cancer.

The study, co-led by researchers at Washington University School of Medicine in St. Louis, appears Oct. 9 in the journal Cell.

These abnormal protein fragments are called neoantigens. The new study identifies five features of neoantigens that optimize the ability to trigger the body’s T cells to attack the cancer and leave healthy tissue untouched. Using the new criteria, the researchers used computer modeling to accurately predict 75% of effective neoantigens and eliminate 98% of ineffective mutant proteins in melanoma and a common type of lung cancer.

The research team, called the Tumor Neoantigen Selection Alliance (TESLA), has made the computer model and dataset freely available to the research community to speed the development of cancer vaccines and other immunotherapies.

“For scientists working to create personalized cancer vaccines that target the unique neoantigens of an individual patient’s tumor, this is a resource that is desperately needed,” said co-senior author Robert D. Schreiber, PhD, the Andrew M. Bursky & Jane M. Bursky Distinguished Professor of Pathology and Immunology. “There has been an explosion of approaches to try and figure out which are the best mutant proteins to target in a tumor. This broad approach is more accurate and will help to design anticancer vaccines that potentially are more effective for patients.”

The features that the researchers identified as most important in selecting effective neoantigens include the abundance of a specific neoantigen in the tumor; the strength with which the neoantigen binds to vital immune proteins so the T cells can see it; the stability of the neoantigen on the immune protein complex; how much more often the immune proteins preferentially bind to the neoantigen versus the normal protein; and how foreign or distinct the neoantigen is from the normal protein.

Schreiber said that all these factors make sense in selecting the best neoantigens, but he was surprised by some of the findings on criteria that were not important for neoantigen effectiveness.

“We were able to eliminate some of the assumptions that we scientists sometimes make about what makes a good neoantigen,” said Schreiber, who also directs the Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs at Washington University School of Medicine. “For example, there has been a general sense that the mutant proteins that make the best neoantigens are the most hydrophobic — meaning they repel water. It turns out, that characteristic didn’t show any relationship to neoantigen effectiveness.”

Schreiber also pointed out that this study is focused on neoantigens that activate what are called CD8 T cells, which he describes as the immune system’s foot soldiers, those responsible for killing the tumor cell. He said future work should focus on neoantigens that also activate a different type of cell, CD4 T cells. Schreiber calls these the generals, cells that stay behind the front lines but direct the foot soldiers in their anti-cancer mission.

“In order to get a good immune response against a tumor, you need to activate both CD4 and CD8 T cells,” Schreiber said. “In future work, we would like to conduct a similar analysis to identify the best neoantigens for triggering the CD4 T cells as well. In designing an effective vaccine, we think we need at least one good CD8 neoantigen and one good CD4 neoantigen to trigger immune rejection of a tumor.”

The TESLA initiative, led by the Parker Institute for Cancer Immunotherapy and the Cancer Research Institute, includes 33 research teams from universities, biotech companies, pharmaceutical companies and nonprofit research institutes.

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A primer on viruses, vaccines and therapies

Since the novel coronavirus SARS-Cov-2 emerged late last year, it has been virtually impossible to consume any news without encountering stories about the virus and how it spreads, potential treatments, and the development of new vaccines.

This deluge of news can be overwhelming, especially for those who aren’t well-versed in virology or immunology. To help equip people to interpret the new information we learn about SARS-Cov-2 every day, Arup Chakraborty, the Robert T. Haslam Professor in Chemical Engineering at MIT, and Andrey Shaw at Genentech sat down early in the pandemic to write a slim book containing an overview of viruses and how they emerge to cause pandemics. The book also explains how our immune system fights viruses, the science of epidemiological models, and how vaccines and therapies work.

The resulting book, “Viruses, Pandemics, and Immunity,” provides important context for anyone who wants to better understand the complexities of the COVID-19 outbreak, as well as past and possible future pandemics, Chakraborty says. The book also provides an outline for creating a more pandemic-resilient world.

“People who read the book will now have a conceptual framework and facts to think about how viruses emerge to cause infectious diseases, how they spread, how we combat them naturally, and how we can combat them with vaccines and therapeutics,” says Chakraborty, who is also a professor of physics and of chemistry, a member of MIT’s Institute for Medical Engineering and Science, and a member of the Ragon Institute of MGH, MIT, and Harvard. “It will give them the framework that they need to debate and consider the current issues, and how we might build a more pandemic-resilient world.”

“It’s very difficult for the public to really get an understanding of the whole picture, and so that’s what our attempt was here,” Shaw says. “We felt that it was important to lay out the scientific framework so that people could make their own decisions about what is going on.”

The book, which was illustrated by Philip J.S. Stork of Oregon Health and Science University, was published by the MIT Press as an ebook on Sept. 8 and will be published as a paperback in February.

Historical perspective

Pandemics have played major roles in the course of human history, especially since humans began living together in closer quarters following the development of agriculture more than 10,000 years ago. Periodic outbreaks of bubonic plague, smallpox, yellow fever, influenza, and other infectious diseases have taken a huge toll on human populations.

During the 20th century, humankind made great strides against infectious disease, due to three major factors: improvements in sanitation, the discovery of antibiotics, and the development of vaccines against many deadly diseases. Because of those advances, many people, especially those living in developed countries, tended to think of major disease outbreaks as a thing of the past.

“This pandemic has reminded us that infectious diseases are an existential threat to humankind and have always been,” Chakraborty says.

As he and Shaw outline in their book, viruses, especially RNA viruses, are well-suited to cause pandemics. One reason for this is that RNA viruses are much more prone to make mistakes in copying their genetic material than DNA viruses are. This allows them to occasionally generate mutations that allow them to jump between species. The SARS-Cov-2 virus is believed to have done just that, likely jumping from bats to humans.

While humans have not previously encountered this particular virus, our immune system does have myriad defenses that can help fend off viral infection. These defenses fall into two main branches—innate and adaptive immunity.

The innate immune system is constantly on the lookout for foreign invaders. Upon encountering viral particles, it deploys a variety of cellular responses that can control the virus. The innate immune system also sends out a distress signal that attracts the specialized cells of the adaptive immune system. These cells, such as “killer T cells,” can launch a response tailored specifically for a particular virus or any pathogen. However, this response takes longer to develop. Once a pathogen has been vanquished, memory T cells, B cells, and antibodies specific to that pathogen continue to circulate, providing immunity to future infection.

Medical advances

While the human body has its own defenses against infection, these don’t always get the job done. Technological advances, especially vaccination, have proven to be a major weapon against infectious disease. The first modern vaccine, which was developed in 1796 to prevent smallpox, consisted of a virus called cowpox, which doesn’t harm humans but is similar enough to smallpox to provoke an immune response against the disease. The term vaccine comes from the Latin word “vaccinus,” meaning “of or from cows.”

The book describes the many types of vaccines, including attenuated vaccines, which consist of a weakened form of a virus or bacterium; vaccines that consist of killed pathogens; and subunit vaccines, which contain just a fragment of a pathogen.

One promising new type of subunit vaccine is RNA vaccines, which are made from RNA that encodes a viral protein. A major advantage of this type of vaccine is that they can be designed very quickly—one pharmaceutical company, Moderna, was able to start phase 1 clinical trials of an RNA vaccine against SARS-Cov-2 just over two months after the virus’ genetic sequence was published. That vaccine is now in phase 3 clinical trials, while dozens more, many based on other strategies, are also in development.

Because we don’t know yet which approaches will work the best for COVID-19, “it is wonderful that many vaccine ideas are being pursued in parallel,” the authors write in their chapter on vaccine development.

One factor that makes the authors optimistic about a SARS-Cov-2 vaccine is that the virus does not mutate rapidly, unlike other RNA viruses such as HIV and influenza. “It may not be so difficult to make a vaccine against it, especially with the extraordinary efforts people are putting into it,” Chakraborty says. He adds that the lessons learned from these intense efforts, and current research on vaccines against highly mutable pathogens, could lead to future advances that make possible vaccines against more difficult viruses such as HIV, which has no effective vaccine even after many decades of research, as well as vaccines against novel mutable viruses that may emerge in the future.

Antiviral drugs have also proven successful against some diseases, such as HIV and hepatitis C. These drugs can target many different stages of the viral life cycle. Some prevent viruses from binding to cell receptors that let them enter cells, while others, such as the reverse transcriptase inhibitors used to treat HIV, prevent the virus from replicating inside cells.

Because it takes so long to develop a new antiviral drug, scientists often try repurposing old drugs when a new virus emerges. Recently the U.S. Food and Drug Administration granted emergency-use authorization for remdesivir, a drug that is believed to interfere with viral replication, to treat COVID-19. Dexamethasone, a corticosteroid that helps reduce inflammation, has also been shown to improve symptoms in some patients.

“When COVID-19 first burst onto the scene, many physicians were really unprepared to treat this. But as the months have passed, we’ve become much more familiar with what’s going on, and we have a better idea how to treat these problems,” Shaw says.

The road ahead

In addition to offering the general public a better understanding of the scientific principles behind viruses, immunity, vaccines, therapies, and epidemiology, Chakraborty and Shaw hope to inspire young people to pursue careers related to those topics. They also hope that the book will help people in policymaking positions to gain a better understanding of the science behind pandemics, to aid them in making decisions that will help combat COVID-19 and potential future disease outbreaks.

“The authors provide a readily accessible introduction to viruses, a class of tiny human pathogens of surprising potential to cause transmissible, sometimes fatal, disease. They speak from a deep understanding of the viruses and the body’s response to viral infections. A great book for people who want to understand why viruses are such a challenge to human life,” says David Baltimore, president emeritus and professor of biology at Caltech, and winner of the 1975 Nobel Prize in Medicine.

Chakraborty and Shaw believe there are many ways to make the world more resilient to future pandemics, including improving early diagnostics, surveillance, and epidemiological modeling; creating more targeted approaches to the development of vaccines and antiviral drugs; making vaccine manufacturing more flexible; and making living spaces, workplaces, and hospitals safer. Success in these areas will require partnerships between government, the pharmaceutical industry and academia, with investments by the government to stimulate the necessary advances, the authors say.

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Georgia News Anchor Becomes First Person to Receive COVID-19 Vaccine Shot in Phase 3 Trial

Dawn said that her injection was "painless" and she was not informed whether she was given the placebo or the vaccine.

Earlier this week, Dr. Anthony Fauci shared that this prospective vaccine is being developed at a speed like never before.

It's "the fastest from the time a virus, a pathogen, was identified to the time it actually goes into a Phase 3 trial, literally in the history of vaccinology in the United States at least, and maybe even throughout the world," he explained during an NIH event on Facebook Live on Monday.

In mid-July, early test results from Phase 1 of the trial reflected potential success, with Fauci calling the trial "very good news."

According to the National Institutes of Health, the vaccine, mRNA-1273, was "generally well tolerated and prompted neutralizing antibody activity in healthy adults."

The vaccine is "designed to induce neutralizing antibodies directed at a portion of the coronavirus 'spike' protein, which the virus uses to bind to and enter human cells," according to a press release.

Phase 2 of the trials began in May, with the third round set to continue into the fall. "We’re going to start the Phase 3 trial in the third or fourth week of July. That is going to take place over the rest of the summer and into the fall. If all goes well and there aren’t any unanticipated bumps in the road, hopefully, we should know whether the vaccine is safe and effective by the end of this calendar year, or the beginning of 2021," Fauci told InStyle.

As of July 30, there have been more than 4.4 million cases of the coronavirus and at least 151,194 deaths, according to recent data from the New York Times.

As information about the coronavirus pandemic rapidly changes, PEOPLE is committed to providing the most recent data in our coverage. Some of the information in this story may have changed after publication. For the latest on COVID-19, readers are encouraged to use online resources from CDC, WHO, and local public health departments. PEOPLE has partnered with GoFundMe to raise money for the COVID-19 Relief Fund, a fundraiser to support everything from frontline responders to families in need, as well as organizations helping communities. For more information or to donate, click here.

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