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Self-Spreading Vaccine Research Could Spin Out of Control, Experts Warn

George Dvorsky wrote . . . . . . . . .

Imagine a future scenario in which a dangerous new virus is detected in chimpanzees. To prevent this virus from spreading to humans, biologists decide to deliberately infect scores of wild chimps with a transmissible vaccine—an infectious, lab-grown virus that immunizes, rather than harms, its host. The chimps, now vaccinated, no longer pose a threat to humans.

That solution sounds too good to be true, which is exactly the problem, as scientists warn in a new Policy Forum published today in Science. Self-spreading vaccines are potentially dangerous and difficult to manage, and are “genetically too unstable to be used safely and predictably outside contained facilities,” write the authors, led by Filippa Lentzos from King’s College London and Guy Reeves from the Max Planck Institute for Evolutionary Biology.

This is not just their opinion, the authors argue. Rather, it’s an “evidence-based norm” that’s been around for decades, but this “norm now seems to be challenged,” they write. The result is an increased potential for “risky research on lab-modified self-spreading viruses,” according to the report. This could lead to a normalization of the concept and eventual real-world use without the proper safeguards, the scientists argue.

“Self-spreading vaccine research continues to proceed despite a lack of new information that would compellingly refute long-standing evidence-based norms in virology, evolutionary biology, vaccine development, international law, public health, risk assessment, and other disciplines,” the biologists write.

Vaccines that spread like a disease are an unquestionably powerful concept. They could be used to protect animals from disease and/or prevent them from harboring viruses dangerous to humans. In 2020, biologists Scott Nuismer and James Bull, both at the University of Idaho, argued for this very approach in a paper titled “Self-disseminating vaccines to suppress zoonoses.” (By self-disseminating virus, scientists mean a virus that has been artificially modified to perform a desired function while retaining its ability to spread between hosts.)

By leveraging the spreading power of viruses, scientists could create biological agents that proliferate quickly through a target population, with the viruses performing specific tasks, such as delivering vaccines or sterilizing invasive species. In the late 1980s, Australian researchers dabbled with lab-modified, contagious viruses, using multiple approaches to exterminate foxes, mice, and rabbits, according to the paper.

More conceptually—and certainly more controversially—this strategy could also be used to spread vaccines among humans.

As the paper points out, interest in this biotechnology has increased significantly over the past several years, with the European Union (through its Horizon 2020 program), the U.S. National Institutes of Health, and the U.S. Defense Advanced Research Projects Agency all currently running programs to explore a wide range of possible applications.

Lentzos, Reeves, and colleagues say it’s time to pump the brakes and consider the consequences of this research and all the moving parts needed to make such a thing work. It’s not immediately clear, they argue, that self-disseminating viruses can be contained or removed from an environment once released, or who would be responsible for the biocontrol agent, should the virus behave unexpectedly or cross national boundaries.

Advocates of the idea say these viruses could be modified to have short lifespans or be made incapable of mutating, but “it remains to be experimentally tested if [manipulations] could simultaneously limit viral replication transmissibility to the extent that they could be perceived as controllable while maintaining sufficient transmissibility to be considered useful as vaccines in continually dynamic environments,” according to the report.

As for using transmissible vaccines to limit the spread of diseases from animals to humans, the scientists say the “the vast majority of virus species that currently exist are undescribed by science,” making it “very difficult to imagine how the considerable effort necessary to develop and test self-spreading vaccines could identify and then prioritize single viral species circulating in wildlife.” That viruses are constantly mutating makes this task all the more onerous, they add.

In terms of what’s needed, the authors call for various safeguards, cost-benefit analyses, and measures such as regulatory oversight. This would involve “a concerted, global governance effort with coherent regional, national, and local implementation.” The essay suggests that national governments update their legislation and guidelines on the matter, while developers and funders of this research “articulate comprehensive and credible regulatory paths through which they believe the safety and efficacy of self-spreading approaches could be established.”

In an email, Bull, co-author of the 2020 paper advocating for research into this biotechnology, said the authors of the new report “raise several valid points,” and he agrees that “informed regulatory oversight is essential,” adding that “public acceptance is also essential.”

“Until we undertake preliminary studies of transmissible vaccines (in contained environments), we will have little evidence on which to base estimated risks and benefits,” Bull told Gizmodo. “It is to be expected that early papers on transmissible vaccines explore the theoretical possibilities, many of which will never be practical or, as further work may show, never be safe.”

In an effort to move ahead cautiously, Bull recommended conservative approaches, such as creating a vaccine from a benign virus that already exists in a target population, as opposed to modifying an otherwise harmful virus. Work into gene drives, a related technology in which modified organisms engineer an entire species, could also help. “Just as gene drive developers have responded to regulatory concerns and have invented new designs with limited potential for spread, it is expected that investment in laboratory studies of transmissible vaccines will also lead to methods that mitigate risks,” Bull argued.

The idea of transmissible vaccines might die on the vine, whether on account of technical issues, safety concerns, or lack of public acceptance. But, clearly, dedicated research attention is needed, since the potential benefits—and risks—are immense.

Source : GIZMODO

Read also at Bulletin of the Atomic Scientists

Scientists are working on vaccines that spread like a disease. What could possibly go wrong? . . . . .

Antibody-dependent Enhancement (ADE) and Vaccines

Immune responses to pathogens involve many cells and proteins of the immune system. Early during an infection, these responses are non-specific, meaning that although they are directed at the pathogen, they are not specific to it. This is called innate immunity. Within a few days, adaptive immunity takes over; this immunity is specific to the invading pathogen. Adaptive immune responses include antibodies. A major goal of antibodies is to bind to the pathogen and prevent it from infecting, or entering, a cell. Antibodies that prevent entry into cells are called neutralizing antibodies. Many vaccines work by inducing neutralizing antibodies. However, not all antibody responses are created equal. Sometimes antibodies do not prevent cell entry and, on rare occasions, they may actually increase the ability of a virus to enter cells and cause a worsening of disease through a mechanism called antibody-dependent enhancement (ADE).

What is ADE?

ADE occurs when the antibodies generated during an immune response recognize and bind to a pathogen, but they are unable to prevent infection. Instead, these antibodies act as a “Trojan horse,” allowing the pathogen to get into cells and exacerbate the immune response.

Importantly, when a vaccinated person subsequently gets infected, this is not automatically evidence of ADE. Specifically, if a vaccinated person gets infected with the pathogen against which the vaccine protects, three different scenarios can occur:

Mild illness – In this scenario, the person may experience some symptoms, but they are more of an inconvenience and last only a few days (typically about 1-3 days). For many respiratory and gastrointestinal infections (e.g., influenza, COVID-19, and rotavirus), this is common. These mild symptoms are evidence that the vaccine worked.

“Breakthrough illness” – Traditionally, this term has been reserved for vaccinated people who get more severely ill, requiring hospitalization or experiencing untoward outcomes, such as disease complications (e.g., pneumonia) or death. In this case, the vaccine may not have worked at all or it did not induce high enough levels of immunity to effectively stop an infection.

ADE – In this scenario, the antibodies that the vaccine generated actually help the virus infect greater numbers of cells than it would have on its own. In this situation, the antibodies bind to the virus and help it more easily get into cells than it would on its own. The result is often more severe illness than if the person had been unvaccinated. ADE can occur after disease and has on occasion been identified following vaccination, as described below. Any vaccine that has been found to cause ADE has stopped being used or, more recently as described below for dengue vaccine, been recommended only for those who will not be affected by ADE. Evidence of ADE has not emerged for COVID-19 vaccines even though concerns have been raised.

Is ADE caused by a disease?

Most diseases do not cause ADE, but one of the best studied examples of a pathogen that can cause ADE is dengue virus. Dengue virus is one of the most common infections in the world, infecting hundreds of millions and killing tens of thousands of people each year. Unlike viruses like measles or mumps that only have one type, dengue virus has four different forms, called “serotypes.” These serotypes are very similar, but slight differences among them set the stage for ADE. If a person is infected by one serotype of dengue virus, they typically have mild disease and generate a protective immune response, including neutralizing antibodies, against that serotype. But, if that person is infected with a second serotype of dengue virus, the neutralizing antibodies generated from the first infection may bind to the virus and actually increase the virus’s ability to enter cells, resulting in ADE and causing a severe form of the disease, called dengue hemorrhagic fever.

Is ADE caused by vaccines?

On a few occasions ADE has resulted from vaccination:

Respiratory syncytial virus (RSV) — RSV is a virus that commonly causes pneumonia in children. A vaccine was made by growing RSV, purifying it, and inactivating it with the chemical formaldehyde. In clinical trials, children who were given the vaccine were more likely to develop or die from pneumonia after infection with RSV. As a result of this finding, the vaccine trials stopped, and the vaccine was never submitted for approval or released to the public.

Measles — An early version of measles vaccine was made by inactivating measles virus using formaldehyde. Children who were vaccinated and later became infected with measles in the community developed high fevers, unusual rash, and an atypical form of pneumonia. Upon seeing these results, the vaccine was withdrawn from use, and those who received this version of the vaccine were recommended to be vaccinated again using the live, weakened measles vaccine, which does not cause ADE and is still in use today.

Both the RSV and measles vaccines that caused ADE were tested in the 1960s. Since then, other vaccines have successfully been created by purifying and chemically inactivating the virus with formaldehyde, such as hepatitis A, rabies, and inactivated polio vaccines. These more recent vaccines do not cause ADE.

A more recent example of ADE following vaccination comes from dengue virus:

Dengue virus — In 2016, a dengue virus vaccine was designed to protect against all four serotypes of the virus. The hope was that by inducing immune responses to all four serotypes at once, the vaccine could circumvent the issues related to ADE following disease with dengue virus. The vaccine was given to 800,000 children in the Philippines. Fourteen vaccinated children died after encountering dengue virus in the community. It is hypothesized that the children developed antibody responses that were not capable of neutralizing the natural virus circulating in the community. As such, the vaccine was recommended only for children greater than 9 years of age who had already been exposed to the virus.

Other viral vaccines that target multiple types of a virus have been safely used, including vaccines against polio (3 types), rotavirus (5 types), and human papillomavirus (9 types).

Should I be concerned that my child will develop ADE after receiving a vaccination?

Today’s routinely recommended vaccines do not cause ADE. If they did, like those described above, they would be removed from use. Phase III clinical trials are designed to uncover frequent or severe side effects before a vaccine is approved for use. Find out more about how vaccines are developed and approved for use.

Can the new COVID-19 vaccines cause ADE?

Neither COVID-19 disease nor the new COVID-19 vaccines have shown evidence of causing ADE. People infected with SARS-CoV-2, the virus that causes COVID-19, have not been likely to develop ADE upon repeat exposure. This is true of other coronaviruses as well. Likewise, studies of vaccines in the laboratory with animals or in the clinical trials in people have not found evidence of ADE.

Following the experience with dengue vaccine, early during the COVID-19 pandemic, concerns about ADE were top of mind. During this time, a few scientists tried to predict whether ADE would occur by evaluating genes for similarities and differences. While this was a useful approach at a time when we did not have much information about what might happen in people, we have since accumulated several lines of clinical evidence that confirm ADE is not an issue for COVID-19 or the vaccines:

People who are infected with SARS-CoV-2, or its variants, do not become more susceptible to ADE.

Many vaccinated people have been exposed to the virus, and its variants, and most of them have developed no disease or mild symptoms. A very small number have experienced more severe disease (“breakthrough infection”), and these individuals have not shown evidence of ADE.

Unfortunately, some people continue to spread misinformation suggesting that ADE is an ongoing concern for COVID-19 vaccines; however, scientists and clinicians are continuing to monitor COVID-19 infections and, to date, no evidence to validate this concern has emerged.

Source : The Children’s Hospital of Philadelphia

What the Polio Vaccines Can Teach Us About the COVID Ones

Peter Skurkiss wrote . . . . . . . . .

Prior to the 1950s, paralytic polio was a scourge. FDR was crippled from it while in his 30s, the March of Dimes was started to combat it, and photos of rows and rows of children in iron lungs were common in the media. From this situation, vaccines were developed to combat the disease.

Polio is caused by one of three types of poliovirus that can cause paralysis and death. In the 1950s, two vaccines were independently developed to combat it, one by Jonas Salk and the other by Albert Sabin. Polio was eradicated, and today those vaccines are thought of as miracle drugs. But were they?

In the early 1950s, Salk was the first to come out with a vaccine. His was designed to treat all three polio viruses at once. His approach seemed basic enough. It was to grow polioviruses in the lab, kill them, and then inject healthy children with the dead viruses. The idea was that the dead viruses could not reproduce, so they could not harm the children. The children’s immune system, however, would detect the injected viruses and produce effective antibodies against them, thus creating immunity against polio.

Just prior to beginning mass inoculations, samples of the Salk vaccine were sent to the National Institutes of Health (NIH) for safety testing.

There, when bacteriologist Dr. Bernice Eddy injected the vaccine into her monkeys, some of them fell down paralyzed. She concluded that the virus was not entirely dead as promised. Instead, the virus was active and could reproduce in its host. Eddy sounded the alarm and presented her findings. A debate ensued in the corridors of power. Advocates for caution were overruled, and the mass inoculation proceeded on schedule.

The inoculation of children began in 1955. Within days, some injected children were coming down with polio. Some were even spreading the disease to family members. Subsequent investigations determined that the vaccine had caused 40,000 cases of polio, leaving 200 children with varying degrees of paralysis and ten dead. Alton Ochsner, a professor of surgery at Tulane Medical School, was such a strong proponent of proceeding with the inoculation program that he gave vaccine injections to his grandchildren to prove that it was safe. Ochsner’s grandson died from polio a few months later, and his granddaughter contracted polio but survived.

This fiasco has become known as the Cutter incident. It’s named after the manufacturer of the vaccine. The vaccine was recalled and retested for safety, but the damage had already been done in the mind of the public.

Let’s continue to the second version of the polio vaccine, the Sabin.

In 1957, inactivated poliovirus vaccine (IPV) and live but weakened oral poliovirus vaccines (OPV) were prepared in primary cell cultures derived from rhesus monkey kidneys.

According to the American Association for Cancer Research, it was later determined that the vaccines made from these cultures were contaminated with the infectious cancer-causing virus SV40. The Centers for Disease Control & Prevention estimates that up to 30 percent of the polio vaccines administered from 1957 to 1963 contained this cancer-causing monkey virus. Dr. Eddy was involved in the discovery of that, too, despite being shunted off to other research after her first discovery.

Did this result in a cancer epidemic? Some believe that it did, as there was a sharp rise in soft tissue cancer in the following decades. The medical establishment disagrees, saying only a “small” number of cancer cases can be traced to the polio vaccines. In any event, it was a fact that a cancer-causing virus was present in the polio vaccines and that the government kept the public in the dark. This was done to avoid mass hysteria and to prevent the wrecking of the public’s confidence in medicine and vaccines in particular.

One result of the damage caused by these initial polio vaccines is that strict new safety regulations and procedures were instituted. Also, legislation was passed to exempt vaccine manufacturers from civil damages due to the side-effects of their vaccines. 42 U.S. Code 300aa-22 — Standard of responsibility states: “No vaccine manufacturer shall be liable in a civil action for damages arising from a vaccine-related injury or death associated with the administration of a vaccine after October 1, 1988.”

Polio is practically unknown today. But is that because of the vaccines or other factors? Note, polio is spread by contact with infected feces, which often happens from poor hand-washing. It can be spread from eating or drinking contaminated food or water. In some cases, it can be spread when an infected person coughs or sneezes infected droplets into the air. It would seem that as hygiene improved and sanitation got better, polio would diminish. This was all known in the 1950s.

Whatever the case, a takeaway lesson from the early polio vaccines is that haste makes waste. Back then, those vaccines were rushed out to the public without being adequately tested due to panic over the disease. One has to wonder if the same sort of thing isn’t happening today with the COVID vaccines. There are similarities between what happened then and what’s unfolding now, chief among them political pressure for a magic-bullet cure. Is it possible or even likely that political pressure has compromised the safety protocols and standard procedures at the FDA and Big Pharma which are there to ensure only safe vaccines are issued for public use? Time will tell.

Source : American Thinker

How Does the Johnson & Johnson Vaccine Compare to Other Coronavirus Vaccines?

Maureen Ferran wrote . . . . . . . . .

1. How does the Johnson & Johnson vaccine work?

The Johnson & Johnson vaccine is what’s called a viral vector vaccine.

To create this vaccine, the Johnson & Johnson team took a harmless adenovirus – the viral vector – and replaced a small piece of its genetic instructions with coronavirus genes for the SARS-CoV-2 spike protein.

After this modified adenovirus is injected into someone’s arm, it enters the person’s cells. The cells then read the genetic instructions needed to make the spike protein and the vaccinated cells make and present the spike protein on their own surface. The person’s immune system then notices these foreign proteins and makes antibodies against them that will protect the person if they are ever exposed to SARS-CoV-2 in the future.

The adenovirus vector vaccine is safe because the adenovirus can’t replicate in human cells or cause disease, and the SARS-CoV-2 spike protein can’t cause COVID–19 without the rest of the coronavirus.

This approach is not new. Johnson & Johnson used a similar method to make its Ebola vaccine, and the AstraZeneca-Oxford COVID-19 vaccine is also an adenovirus viral vector vaccine.

2. How effective is it?

The FDA’s analysis found that, in the U.S., the Johnson & Johnson COVID-19 vaccine was 72% effective at preventing all COVID-19 and 86% effective at preventing severe cases of the disease. While there is still a chance a vaccinated person could get sick, this suggests they would be much less likely to need hospitalization or to die from COVID-19.

A similar trial in South Africa, where a new, more contagious variant is dominant, produced similar results. Researchers found the Johnson & Johnson vaccine to be slightly less effective at preventing all illness there – 64% overall – but was still 82% effective at preventing severe disease. The FDA report also indicates that the vaccine protects against other variants from Britain and Brazil too.

3. How is it different from other vaccines?

The most basic difference is that the Johnson & Johnson vaccine is an adenovirus vector vaccine, while the Moderna and Pfizer vaccines are both mRNA vaccines. Messenger RNA vaccines use genetic instructions from the coronavirus to tell a person’s cells to make the spike protein, but these don’t use another virus as a vector. There are many practical differences, too.

Both of the mRNA-based vaccines require two shots. The Johnson & Johnson vaccine requires only a single dose. This is key when vaccines are in short supply.

The Johnson & Johnson vaccine can also be stored at much warmer temperatures than the mRNA vaccines. The mRNA vaccines must be shipped and stored at below–freezing or subzero temperatures and require a complicated cold chain to safely distribute them. The Johnson & Johnson vaccine can be stored for at least three months in a regular refrigerator, making it much easier to use and distribute.

As for efficacy, it is difficult to directly compare the Johnson & Johnson vaccine with the mRNA vaccines due to differences in how the clinical trials were designed. While the Moderna and Pfizer vaccines are reported to be approximately 95% effective at preventing illness from COVID–19, the trials were done over the summer and fall of 2020, before newer more contagious variants were circulating widely. The Moderna and Pfizer vaccines might not be as effective against the new variants, and Johnson & Johnson trials were done more recently and take into account the vaccine’s efficacy against these new variants.

4. Should I choose one vaccine over another?

Although the overall efficacy of the Moderna and Pfizer vaccines is higher than the Johnson & Johnson vaccine, you should not wait until you have your choice of vaccine – which is likely a long way off anyway. The Johnson & Johnson vaccine is nearly as good as the mRNA-based vaccines at preventing serious disease, and that’s what really matters.

The Johnson & Johnson vaccine and other viral-vector vaccines like the one from AstraZeneca are particularly important for the global vaccination effort. From a public health perspective, it’s important to have multiple COVID-19 vaccines, and the Johnson & Johnson vaccine is a very welcome addition to the vaccine arsenal. It doesn’t require a freezer, making it much easier to ship and store. It’s a one-shot vaccine, making logistics much easier compared with organizing two doses per person.

As many people as possible need to be vaccinated as quickly as possible to limit the development of new coronavirus variants. Johnson & Johnson is expected to ship out nearly four million doses as soon as the FDA grants emergency use authorization. Having a third authorized vaccine in the U.S. will be a big step towards meeting vaccination demand and stopping this pandemic.

Source : The Conversation

Denmark, Norway Temporarily Suspend AstraZeneca COVID Shots After Blood Clot Reports

Nikolaj Skydsgaard and Jacob Gronholt-Pedersen wrote . . . . . . . . .

Health authorities in Denmark and Norway said on Thursday they had temporarily suspended the use of AstraZeneca’s COVID-19 vaccine shots after reports of the formation of blood clots in some who have been vaccinated.

The move comes after Austria stopped using a batch of AstraZeneca shots while investigating a death from coagulation disorders and an illness from a pulmonary embolism.

Danish health authorities said the country’s decision to suspend the shots for two weeks came after a 60-year old woman in Denmark, who was given an AstraZeneca shot from the same batch that was used in Austria, formed a blood clot and died.

Danish authorities said they had responded “to reports of possible serious side effects, both from Denmark and other European countries.”

“It is currently not possible to conclude whether there is a link. We are acting early, it needs to be thoroughly investigated,” Health Minister Magnus Heunicke said on Twitter.

The vaccine would be suspended for 14 days in Denmark.

“This is a cautionary decision,” Geir Bukholm, director of infection prevention and control at the Norwegian Institute of Public Health (FHI), told a news conference.

FHI did not say how long the suspension would last.

“We … await information to see if there is a link between the vaccination and this case with a blood clot,” Bukholm said.

Also on Thursday, Italy said it would suspend use of an AstraZeneca batch that was different to the one used in Austria.

Some health experts said there was little evidence to suggest the AstraZeneca vaccine should not be administered and that the cases of blood clots corresponded with the rate of such cases in the general population.

“This is a super-cautious approach based on some isolated reports in Europe,” Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, told Reuters.

“The problem with spontaneous reports of suspected adverse reactions to a vaccine are the enormous difficulty of distinguishing a causal effect from a coincidence,” he said, adding that the COVID-19 disease was very strongly associated with blood clotting.

AstraZeneca on Thursday told Reuters in a written statement the safety of its vaccine had been extensively studied in human trials and peer-reviewed data had confirmed the vaccine was generally well tolerated.

The drugmaker said earlier this week its shots were subject to strict and rigorous quality controls and that there had been “no confirmed serious adverse events associated with the vaccine”. It said it was in contact with Austrian authorities and would fully support their investigation.

The European Union’s drug regulator, the European Medicines Agency (EMA), said on Wednesday there was no evidence so far linking AstraZeneca to the two cases in Austria.

It said the number of thromboembolic events – marked by the formation of blood clots – in people who have received the AstraZeneca vaccine is no higher than that seen in the general population, with 22 cases of such events being reported among the 3 million people who have received it as of March 9.

EMA was not immediately available for comment on Thursday.

Four other countries – Estonia, Lithuania, Luxembourg and Latvia – have stopped inoculations from the batch while investigations continue, the EMA said.

The batch of 1 million doses went to 17 EU countries.

Swedish authorities said they did not find sufficient evidence to stop vaccination with AstraZeneca’s vaccine. Sweden has found two cases of “thromboembolic events” in connection with AstraZeneca’s vaccine and about ten for the Pfizer-BioNTech vaccine.

“We see no reason to revise our recommendation,” Veronica Arthurson, head of drug safety at the Swedish Medical Products Agency, told a news conference. “There is nothing to indicate that the vaccine causes this type of blood clots.”

Spain on Thursday said it had not registered any cases of blood clots related to AstraZeneca’s vaccine so far and would continue administering the shots.

Source : Reuters

Chart of the Day: Should COVID-19 Vaccination Be Mandatory?

Source : Statista

How Many People Need to Get a COVID-19 Vaccine in Order to Stop the Coronavirus?

Pedro Mendes wrote . . . . . . . . .

It has been clear for a while that, at least in the U.S., the only way out of the coronavirus pandemic will be through vaccination. The rapid deployment of coronavirus vaccines is underway, but how many people need to be vaccinated in order to control this pandemic?

I am a computational biologist who uses data and computer models to answer biological question at the University of Connecticut. I have been tracking my state’s COVID-19 epidemic with a computer model to help forecast the number of hospitalizations at the University of Connecticut’s John Dempsey Hospital.

This type of computer model and the underlying theory can also be used to calculate the vaccination rates needed to break the chain of transmission of the coronavirus. My estimate is that for the entire U.S., roughly 70% of the population needs to be vaccinated to stop the pandemic. But variation in how people behave in different parts of the country, as well as open questions on whether the vaccine prevents infection entirely or just prevents people from getting sick, add a degree of uncertainty.

Cutting off transmission

Clinical trials have shown that once a person gets vaccinated for the coronavirus, they won’t get sick with COVID-19. A person who doesn’t get sick can still be infected with the coronavirus. But let’s also assume that a vaccinated person can’t spread the virus to others, though researchers still don’t know if this is true.

When enough of the population is vaccinated, the virus has a hard time finding new people to infect, and the epidemic starts dying out. And not everyone needs to be vaccinated, just enough people to stop the virus from spreading out of control. The number of people who need to be vaccinated is known as the critical vaccination level. Once a population reaches that number, you get herd immunity. Herd immunity is when there are so many vaccinated people that an infected person can hardly find anyone who could get infected, and so the virus cannot propagate to other people. This is very important to protect people who cannot get vaccinated.

The critical vaccination level depends on how infectious the disease is and how effective the vaccine is. Infectiousness is measured using the basic reproduction number – R0 – which is how many people an infected person would spread the virus to on average if no protective measures were in place.

The more infectious a disease is, the larger the number of people who need to be vaccinated to reach heard immunity. The higher the effectiveness of the vaccine, the fewer people need to be vaccinated.

Not the same everywhere

R0 values differ from place to place because their populations behave differently – social interactions are not the same in rural and urban locations, nor in warm climates compared to cold ones, for example.

Using the data on positive cases, hospitalizations and deaths, my model estimates that Connecticut currently has an R0 of 2.88, meaning that, on average, every infected person would pass the virus on to 2.88 other people if no mitigation measures were in place. Estimates at the county level range from 1.44 in rural Alpine, California to 4.31 in urban Hudson, New Jersey.

But finding an R0 value for the entire U.S. is especially tricky because of the diversity of climates and because the virus has affected different areas at different times – behavior has been far from uniform. Estimates vary from 2.47 to 8.2, though most researchers place R0 for the entire U.S. around 3.

While R0 varies by location and between estimates, the effectiveness of the vaccines is constant and well known. The Pfizer-BioNTech and Moderna vaccines are 95% and 94.5% effective at preventing COVID-19, respectively.

Using values for vaccine effectiveness and the R0, we can calculate the critical vaccination level. For Connecticut, with an R0 of 2.88, 69% of the population needs to be vaccinated. For the entire U.S., with R0 of 3, this would be 70%. In New York City, with an estimated R0 of 4.26 this would be 80%.

A lot of uncertainty

While the math is relatively simple, things get complicated when you consider important questions for which epidemiologists still have no answers.

First, the formula for critical vaccination level assumes that people interact randomly. But in the real world, people interact in highly structured networks depending on work, travel and social connections. When those contact patterns are considered, some researchers found critical vaccination levels to be considerably smaller compared to assuming random interactions.

Unfortunately, other unknowns could have an opposite effect.

Vaccine trials clearly show that vaccinated people don’t get sick with COVID-19. But it is still unknown whether the vaccines prevent people from getting mild infections that they could pass on to others. If vaccinated people can still be infected and pass on the virus, then vaccination will not provide herd immunity – though it would still prevent serious disease and reduce mortality drastically.

A final question that remains to be answered is how long immunity to the coronavirus lasts after a person is vaccinated. If immunity wanes after a few months, then each individual will need repeated vaccinations.

It is hard to say with certainty how many people need to be vaccinated in order to end this pandemic. But even so, the arrival of COVID-19 vaccines has been the best news in 2020. In 2021, as a large proportion of individuals in the U.S. get the vaccine, the country will be heading toward the critical vaccination level – whatever it may be – so that life can start to return to normal.

Source : The Conversation

Israel Walks Back Reported Virus Czar Claim that Pfizer 1st Dose Less Effective

The Health Ministry on Friday walked back apparent claims by Israel’s virus czar that the first dose of Pfizer’s vaccine provides less protection against COVID-19 than the US pharmaceutical firm had initially indicated it would, saying his words had been quoted out of context.

Earlier this week, Army Radio reported that Nachman Ash had, in a meeting with health officials, noted that many people have gotten infected between the first and second Pfizer shots and questioned the effectiveness of the vaccine after just one dose. The data on the protective effect against the virus of the first dose is “lower than Pfizer presented,” he was quoted saying.

Pfizer says its vaccine, produced with BioNTech, is around 52% effective after the first dose, and increases to about 95% a number of days after the second dose.

In a statement issued Friday, the Health Ministry said reports regarding the czar’s comments were “out of context and not accurate.”

“The vaccination campaign in Israel started a month ago… during a surge in morbidity and mortality in the country, which makes it hard to evaluate vaccination effectiveness without biases,” the ministry said. “Initial evaluation reveals some protective effects of the vaccine and those are carefully studied by the Health Ministry.”

“The commissioner said we have yet to see a decrease in the number of severely ill patients. As the second dose is given these days to at-risk populations we expect to see the full protective impact of the vaccine,” the statement said.

The Health Ministry also announced Friday that it had broken a record in daily vaccinations on Thursday, with 244,000 Israelis getting inoculated.

Ministry figures showed 2,441,379 Israelis have received the first vaccine dose and 850,811 of them the second.

Israel is leading the world in vaccination on a per capita basis, according to the Oxford-based Our World in Data.

More than a month into Israel’s vaccination campaign, Health Ministry officials had hoped to see a dramatic drop in daily infections and serious cases, but there is no such trend at this time. The more contagious virus variants — particularly the British strain — are being blamed for the difficulty in bringing down illness rates and easing the heavy load on hospitals, despite the lockdown and mass vaccinations.

The ministry also reported a slight decline in daily coronavirus infections, as Israel’s worst outbreak since the pandemic began appeared to ease after weeks of strict lockdown rules.

According to the ministry, 7,099 new cases were confirmed Thursday, after peaking at over 10,100 earlier in the week. Along with another 1,228 cases since midnight, the total number of infections recorded in Israel reached 585,746.

The drop in daily cases came as testing levels also further decreased, though the positive test rate fell to 8.9 percent.

The death toll stood at 4,245, with 27 fatalities recorded Thursday.

The ministry said there were 82,029 active cases, with 1,845 patients hospitalized for COVID-19. Of those, 1,128 were in serious condition, with 310 on ventilators.

Source : The Times of Israel

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Nachman Ash reportedly says it’s not certain vaccines can protect against mutated coronavirus strains; 12,400 Israelis were infected with virus after receiving 1st shot . . . . .

British Scientists Developing World’s First Covid-19 Vaccine Smart Patch

Emily Brown wrote . . . . . . . . .

Scientists from Swansea University in Wales are striving to develop the first coronavirus vaccine ‘smart patch’.

The patch will use microneedles to both administer the coronavirus vaccine and monitor its efficacy for the patient by tracking the body’s immune response.

The research team plans to develop a prototype by the end of March, in the hope it can be put forward for clinical trials and ultimately released to the public, as part of the effort to tackle the coronavirus outbreak.

Scientists at Swansea’s IMPACT research centre hope to carry out human clinical studies in partnership with Imperial College London with the aim of making the device commercially available within three years.

Using polycarbonate or silicon millimetre-long microneedles, the smart patch can penetrate the skin to administer a vaccine. It can be held in place with a strap or tape for up to 24 hours, during which time it simultaneously measures a patient’s inflammatory response to the vaccination by monitoring biomarkers in the skin.

Once the vaccine has been administered, the device is scanned to produce a data reading that can provide an understanding about the efficacy of the vaccine and the body’s response to it.

Those involved in the project received Welsh government and European funding as part of the global response to overcome the coronavirus pandemic, though scientists hope the smart patch could also be used to treat other infectious diseases, the BBC reports.

Medical engineering lecturer Dr Sanjiv Sharma explained the body’s production of immunoglobulins – antibodies that form a critical part of our immune defences – are ‘good markers’ of showing the efficacy of vaccination.

Discussing the smart patch, Sharma said the scientists expect to see the production of immunoglobulins in response to the self-administration of the device.

He continued:

This low-cost vaccine administration device will ensure a safe return to work and management of subsequent Covid-19 outbreaks.

Beyond the pandemic, the scope of this work could be expanded to apply to other infectious diseases as the nature of the platform allows for quick adaption to different infectious diseases.

There are currently no other devices commercially available that provide vaccines in this manner, though Sharma said the patch is similar to ‘continuous glucose monitoring sensors’ used by people with diabetes.

The device may serve as a more desirable way for people who are scared of injections to receive the vaccine, as PhD student Olivia Howells explained the patch does not penetrate as deeply as needles. Howells added that the patches are cheaper than hypodermic needles, meaning they could be useful in countries struggling with resources for vaccination.

Source : Uilad

How mRNA Went from a Scientific Backwater to a Pandemic Crusher

David Cox wrote . . . . . . . . .

In 1995, Katalin Karikó was at her lowest ebb. A biochemist at the University of Pennsylvania (UPenn), Karikó had dedicated much of the previous two decades to finding a way to turn one of the most fundamental building blocks of life, mRNA, into a whole new category of therapeutics.

More often than not, Karikó found herself hitting dead ends. Numerous grant applications were rejected, and an attempt to raise funding from venture capitalists in New York to form a spin-off company had proved to be a fruitless endeavour. ”They initially promised to give us money, but then they never returned my phone calls,” she says.

By the mid 1990s, Karikó’s bosses at UPenn had run out of patience. Frustrated with the lack of funding she was generating for her research, they offered the scientist a bleak choice: leave or be demoted. It was a demeaning prospect for someone who had once been on the path to a full professorship. For Karikó’s dreams of using mRNA to create new vaccines and drugs for many chronic illnesses, it seemed to be the end of the road.

Thirty four years earlier, the discovery of mRNA had been announced amidst a clamour of scientific excitement in the summer of 1961. For more than a decade, researchers in the US and Europe had been attempting to unravel exactly how DNA is involved in the creation of proteins – the long strings of amino acids that are vital to the growth and functioning of all life forms.

It transpired that mRNA was the answer. These molecules act like digital tape recorders, repeatedly copying instructions from DNA in the cell nucleus, and carrying them to protein-making structures called ribosomes. Without this key role, DNA would be nothing but a useless string of chemicals, and so some have dubbed mRNA the ‘software of life.’

At the time the nine scientists credited with discovering mRNA were purely interested in solving a basic biological mystery, but by the 1970s the scientific world had begun to wonder if it could exploit this cellular messaging system to turn our bodies into medicine-making factories.

Artificial mRNA, designed and created in a petri dish and then delivered to the cells of sick patients through tiny packages called nanoparticles, offered a way of instructing the body to heal itself. Research groups around the world began looking into whether mRNA could be used to create the vaccines of the future by delivering messages to cells, teaching them to create specific antibodies to fight off a viral infection. Others started investigating whether mRNA could help the immune system recognise and destroy cancerous tissue.

Karikó was first exposed to these ideas as an undergraduate student in 1976, during a lecture at the University of Szeged in her native Hungary. Intrigued, she began a PhD, studying how mRNA might be used to target viruses. While the concept of gene therapy was also beginning to take off at the same time, capturing the imagination of many scientists, she felt mRNA had the potential to help many more people.

“I always thought that the majority of patients don’t actually need new genes, they need something temporary like a drug, to cure their aches and pains,” she said. “So mRNA was always more interesting to me.”

At the time, the technology required to make such grand ambitions a reality did not yet exist. While scientists knew how to isolate mRNA from cells, creating artificial forms was not possible. But in 1984, the American biochemist Kary Mullis invented polymerase chain reaction (PCR), a method of amplifying very small amounts of DNA so it can be studied in detail. By 1989, other researchers had found a way to utilise PCR to generate mRNA from scratch, by amplifying DNA strands and using an enzyme called RNA polymerase to create mRNA molecules from these strands. “For scientists working on mRNA, this was very empowering,” said Karikó. “Suddenly we felt like we could do anything.”

With an mRNA boom taking place on the other side of the Atlantic, Karikó decided it was time to leave Hungary and head for the US. So in 1985, she accepted a job at Temple University and moved to Philadelphia along with her husband, two year old daughter, and a teddy bear with £900 sewn into it – the proceeds from the sale of their car on the black market.

It did not take long for the American dream to sour. After four years, she was forced to leave Temple University for neighbouring UPenn after a dispute with her boss, who then attempted to have her deported. There she began working on mRNA therapies which could be used to improve blood vessel transplants, by producing proteins to keep the newly transplanted vessels alive.

However, by the early to mid 1990s, some of the early excitement surrounding mRNA was beginning to fade. While scientists had cracked the problem of how to create their own mRNA, a new hurdle had emerged. When they injected it into animals it induced such a severe inflammatory response from the immune system that they died immediately. Any thoughts of human trials were impossible.

This was a serious problem, but one Karikó was determined to solve. She recalls spending one Christmas and New Year’s Eve conducting experiments and writing grant applications. But many other scientists were turning away from the field, and her bosses at UPenn felt mRNA had shown itself to be impractical and she was wasting her time. They issued an ultimatum, if she wanted to continue working with mRNA she would lose her prestigious faculty position, and face a substantial pay cut.

”It was particularly horrible as that same week, I had just been diagnosed with cancer,” said Karikó. “I was facing two operations, and my husband, who had gone back to Hungary to pick up his green card, had got stranded there because of some visa issue, meaning he couldn’t come back for six months. I was really struggling, and then they told me this.”

While undergoing surgery, Karikó assessed her options. She decided to stay, accept the humiliation of being demoted, and continue to doggedly pursue the problem. This led to a chance meeting which would both change the course of her career, and that of science.

In 1997, Drew Weissman, a respected immunologist, moved to UPenn. This was long before the days where scientific publications were available online, and so the only way for scientists to peruse the latest research was to photocopy it from journals. “I found myself fighting over a photocopy machine in the department with this scientist called Katalin Karikó,” he remembered. ”So we started talking, and comparing what each other did.”

While Karikó’s academic status at UPenn remained lowly, Weissman had the funding to finance her experiments, and the two began a partnership. “This gave me optimism, and kept me going,” she said. “My salary was lower than the technician who worked next to me, but Drew was supportive and that’s what I concentrated on, not the roadblocks I’d had to face.”

Karikó and Weissman realised that the key to creating a form of mRNA which could be administered safely, was to identify which of the underlying nucleosides – the letters of RNA’s genetic code – were provoking the immune system and replace them with something else. In the early 2000s, Karikó happened across a study which showed that one of these letters, Uridine, could trigger certain immune receptors. It was the crucial piece of information she had been searching for.

In 2005, Karikó and Weissman published a study announcing a specifically modified form of mRNA, which replaced Uridine with an analog – a molecule which looked the same, but did not induce an immune response. It was a clever biological trick, and one which worked. When mice were injected with this modified mRNA, they lived. “I just remember Drew saying, ’Oh my god, it’s not immunogenic,’” said Karikó. “We realised at that moment that this would be very important, and it could be used in vaccines and therapies. So we published a paper, filed a patent, established a company, and then found there was no interest. Nobody invited us anywhere to talk about it, nothing.”

Unbeknown to them, however, some scientists were paying attention. Derrick Rossi, then a postdoctoral researcher at Stanford University, read Karikó and Weissman’s paper and was immediately intrigued. In 2010, Rossi co-founded a biotech company called Moderna, with a group of Harvard and MIT professors, with the specific aim of using modified mRNA to create vaccines and therapeutics. A decade on, Moderna is now one of the leaders in the Covid-19 vaccine race and valued at approximately $35 billion (£26b), after reporting that its mRNA based vaccine showed 94 per cent efficacy in a Phase III clinical trial.

But it was not novel infectious disease vaccines which got the world interested in mRNA again. Around the same time, Rossi was establishing Moderna, Karikó and Weissman were also finally managing to commercialise their finding, licensing their technology to a small German company called BioNTech, after five years of trying and failing.

Both Moderna and BioNTech – which had been founded by a Turkish born entrepreneur called Ugur Sahin – had their eye on the lucrative fields of cancer immunotherapy, cardiovascular and metabolic diseases. Now that Karikó and Weissman’s discovery made it possible to safely administer mRNA to patients, some of the original goals for mRNA back in the 1970s, had become viable possibilities again.

Vaccines were also on the horizon. In 2017, Moderna began developing a potential Zika virus vaccine, while in 2018 BioNTech entered into a partnership with Pfizer to develop mRNA vaccines for influenza, although the large scale funding which drives vaccine projects was still nowhere to be seen.

That has all changed in 2020. With the Covid-19 pandemic requiring vaccine development on an unprecedented scale, mRNA vaccine approaches held a clear advantage over the more traditional but time consuming method of using a dead or inactivated form of the virus to create an immune response. In April, Moderna received $483 million (£360m) from the US Biomedical Advanced Research and Development Authority to fasttrack its Covid-19 vaccine program.

Karikó has been at the helm of BioNTech’s Covid-19 vaccine development. In 2013, she accepted an offer to become Senior Vice President at BioNTech after UPenn refused to reinstate her to the faculty position she had been demoted from in 1995. “They told me that they’d had a meeting and concluded that I was not of faculty quality,” she said. ”When I told them I was leaving, they laughed at me and said, ‘BioNTech doesn’t even have a website.’”

Now, BioNTech is a household name, following reports last month that the mRNA Covid-19 vaccine it has co-developed with Pfizer works with more than 95 per cent efficacy. Along with Moderna, it is set to supply billions of doses around the globe by the end of 2021.

For Karikó, seeing the results of BioNTech’s Phase III trial, simply brought a sense of quiet satisfaction. “I didn’t jump or scream,” she said. “I expected that it would be very effective.”

But after so many years of adversity, and struggling to convince people that her research was worthwhile, she is still trying to comprehend the fact that her breakthrough in mRNA technology could now change the lives of billions around the world, and help end the global pandemic.

“I always wanted to help people, to try and get something into the clinic,” she said. “That was the motivation for me, and I was always optimistic. But to help that many people, I never imagined that. It makes me very happy to know that I’ve played a part in this success story.”

Source : WIRED