COVID-19 Nasal Vaccine Candidate Effective at Preventing Disease Transmission

Laurie Fickman wrote . . . . . . . . .

Breathe in, breathe out. That’s how easy it is for SARS-CoV-2, the virus that causes COVID-19, to enter your nose. And though remarkable progress has been made in developing intramuscular vaccines against SARS-CoV- 2, such as the readily available Pfizer, Moderna and Johnson & Johnson vaccines, nothing yet – like a nasal vaccine – has been approved to provide mucosal immunity in the nose, the first barrier against the virus before it travels down to the lungs.

But now, we’re one step closer.

Navin Varadarajan, University of Houston M.D. Anderson Professor of Chemical and Biomolecular Engineering, and his colleagues, are reporting in iScience the development of an intranasal subunit vaccine that provides durable local immunity against inhaled pathogens.

“Mucosal vaccination can stimulate both systemic and mucosal immunity and has the advantage of being a non-invasive procedure suitable for immunization of large populations,” said Varadarajan. “However, mucosal vaccination has been hampered by the lack of efficient delivery of the antigen and the need for appropriate adjuvants that can stimulate a robust immune response without toxicity.”

To solve those problems, Varadarajan collaborated with Xinli Liu, associate professor of pharmaceutics at the UH College of Pharmacy, and an expert in nanoparticle delivery. Liu’s team was able to encapsulate the agonist of the stimulator of interferon genes (STING) within liposomal particles to yield the adjuvant named NanoSTING. The function of the adjuvant is to promote the body’s immune response.

“NanoSTING has a small particle size around 100 nanometers which exhibits significantly different physical and chemical properties to the conventional adjuvant,” said Liu.

“We used NanoSTING as the adjuvant for intranasal vaccination and single-cell RNA-sequencing to confirm the nasal-associated lymphoid tissue as an inductive site upon vaccination. Our results show that the candidate vaccine formulation is safe, produces rapid immune responses – within seven days – and elicits comprehensive immunity against SARS-CoV-2,” said Varadarajan.

A fundamental limitation of intramuscular vaccines is that they are not designed to elicit mucosal immunity. As prior work with other respiratory pathogens like influenza has shown, sterilizing immunity to virus re-infection requires adaptive immune responses in the respiratory tract and the lung.

The nasal vaccine will also serve to equitably distribute vaccines worldwide, according to the researchers. It is estimated that first world countries have already secured and vaccinated multiple intramuscular doses for each citizen while billions of people in countries like India, South Africa, and Brazil with large outbreaks are currently not immunized. These outbreaks and viral spread are known to facilitate viral evolution leading to decreased efficacy of all vaccines.

“Equitable distribution requires vaccines that are stable and that can be shipped easily. As we have shown, each of our components, the protein (lyophilized) and the adjuvant (NanoSTING) are stable for over 11 months and can be stored and shipped without the need for freezing,” said Varadarajan.

Source: University of Houston

Study: COVID-19 Virus Is Evolving to Get Better at Becoming Airborne

Results of a new study led by the University of Maryland School of Public Health show that people infected with the virus that causes COVID-19 exhale infectious virus in their breath – and those infected with the Alpha variant (the dominant strain circulating at the time this study was conducted) put 43 to 100 times more virus into the air than people infected with the original strains of the virus. The researchers also found that loose-fitting cloth and surgical masks reduced the amount of virus that gets into the air around infected people by about half. The study was published in Clinical Infectious Diseases.

“Our latest study provides further evidence of the importance of airborne transmission,” said Dr. Don Milton, professor of environmental health at the University of Maryland School of Public Health (UMD SPH). “We know that the Delta variant circulating now is even more contagious than the Alpha variant. Our research indicates that the variants just keep getting better at travelling through the air, so we must provide better ventilation and wear tight-fitting masks, in addition to vaccination, to help stop spread of the virus.”

The amount of virus in the air coming from Alpha variant infections was much more—18-times more—than could be explained by the increased amounts of virus in nasal swabs and saliva. One of the lead authors, doctoral student Jianyu Lai explained that, “We already knew that virus in saliva and nasal swabs was increased in Alpha variant infections. Virus from the nose and mouth might be transmitted by sprays of large droplets up close to an infected person. But, our study shows that the virus in exhaled aerosols is increasing even more.” These major increases in airborne virus from Alpha infections occurred before the Delta variant arrived and indicate that the virus is evolving to be better at travelling through the air.

To test whether face masks work in blocking the virus from being transmitted among people, this study measured how much SARS-CoV-2 is breathed into the air and tested how much less virus people sick with COVID-19 exhaled into the air after putting on a cloth or surgical mask. Face coverings significantly reduced virus-laden particles in the air around the person with COVID-19, cutting the amount by about 50%. Unfortunately, the loose-fitting cloth and surgical masks didn’t stop infectious virus from getting into the air.

Dr. Jennifer German, a co-author said, “The take-home messages from this paper are that the coronavirus can be in your exhaled breath, is getting better at being in your exhaled breath, and using a mask reduces the chance of you breathing it on others.” This means that a layered approach to control measures (including improved ventilation, increased filtration, UV air sanitation, and tight-fitting masks, in addition to vaccination) is critical to protect people in public-facing jobs and indoor spaces.

Source: University of Maryland School of Medicine

New Studies Find Evidence Of ‘Superhuman’ Immunity To COVID-19 In Some Individuals

Michaeleen Doucleff wrote . . . . . . . . .

Some scientists have called it “superhuman immunity” or “bulletproof.” But immunologist Shane Crotty prefers “hybrid immunity.”

“Overall, hybrid immunity to SARS-CoV-2 appears to be impressively potent,” Crotty wrote in commentary in Science back in June.

No matter what you call it, this type of immunity offers much-needed good news in what seems like an endless array of bad news regarding COVID-19.

Over the past several months, a series of studies has found that some people mount an extraordinarily powerful immune response against SARS-CoV-2, the coronavirus that causes the disease COVID-19. Their bodies produce very high levels of antibodies, but they also make antibodies with great flexibility — likely capable of fighting off the coronavirus variants circulating in the world but also likely effective against variants that may emerge in the future.

Immunity To COVID-19 Could Last Longer Than You’d Think

“One could reasonably predict that these people will be quite well protected against most — and perhaps all of — the SARS-CoV-2 variants that we are likely to see in the foreseeable future,” says Paul Bieniasz, a virologist at Rockefeller University who helped lead several of the studies.

In a study published online last month, Bieniasz and his colleagues found antibodies in these individuals that can strongly neutralize the six variants of concern tested, including delta and beta, as well as several other viruses related to SARS-CoV-2, including one in bats, two in pangolins and the one that caused the first coronavirus pandemic, SARS-CoV-1.

“This is being a bit more speculative, but I would also suspect that they would have some degree of protection against the SARS-like viruses that have yet to infect humans,” Bieniasz says.

So who is capable of mounting this “superhuman” or “hybrid” immune response?

People who have had a “hybrid” exposure to the virus. Specifically, they were infected with the coronavirus in 2020 and then immunized with mRNA vaccines this year. “Those people have amazing responses to the vaccine,” says virologist Theodora Hatziioannou at Rockefeller University, who also helped lead several of the studies. “I think they are in the best position to fight the virus. The antibodies in these people’s blood can even neutralize SARS-CoV-1, the first coronavirus, which emerged 20 years ago. That virus is very, very different from SARS-CoV-2.”

In fact, these antibodies were even able to deactivate a virus engineered, on purpose, to be highly resistant to neutralization. This virus contained 20 mutations that are known to prevent SARS-CoV-2 antibodies from binding to it. Antibodies from people who were only vaccinated or who only had prior coronavirus infections were essentially useless against this mutant virus. But antibodies in people with the “hybrid immunity” could neutralize it.

These findings show how powerful the mRNA vaccines can be in people with prior exposure to SARS-CoV-2, she says. “There’s a lot of research now focused on finding a pan-coronavirus vaccine that would protect against all future variants. Our findings tell you that we already have it.

“But there’s a catch, right?” she adds: You first need to be sick with COVID-19. “After natural infections, the antibodies seem to evolve and become not only more potent but also broader. They become more resistant to mutations within the [virus].”

Hatziioannou and colleagues don’t know if everyone who has had COVID-19 and then an mRNA vaccine will have such a remarkable immune response. “We’ve only studied the phenomena with a few patients because it’s extremely laborious and difficult research to do,” she says.

But she suspects it’s quite common. “With every single one of the patients we studied, we saw the same thing.” The study reports data on 14 patients.

Several other studies support her hypothesis — and buttress the idea that exposure to both a coronavirus and an mRNA vaccine triggers an exceptionally powerful immune response. In one study, published last month in The New England Journal of Medicine, scientists analyzed antibodies generated by people who had been infected with the original SARS virus — SARS-CoV-1 — back in 2002 or 2003 and who then received an mRNA vaccine this year.

Remarkably, these people also produced high levels of antibodies and — it’s worth reiterating this point from a few paragraphs above — antibodies that could neutralize a whole range of variants and SARS-like viruses.

Now, of course, there are so many remaining questions. For example, what if you catch COVID-19 after you’re vaccinated? Or can a person who hasn’t been infected with the coronavirus mount a “superhuman” response if the person receives a third dose of a vaccine as a booster?

Hatziioannou says she can’t answer either of those questions yet. “I’m pretty certain that a third shot will help a person’s antibodies evolve even further, and perhaps they will acquire some breadth [or flexibility], but whether they will ever manage to get the breadth that you see following natural infection, that’s unclear.”

Immunologist John Wherry, at the University of Pennsylvania, is a bit more hopeful. “In our research, we already see some of this antibody evolution happening in people who are just vaccinated,” he says, “although it probably happens faster in people who have been infected.”

In a recent study, published online in late August, Wherry and his colleagues showed that, over time, people who have had only two doses of the vaccine (and no prior infection) start to make more flexible antibodies — antibodies that can better recognize many of the variants of concern.

So a third dose of the vaccine would presumably give those antibodies a boost and push the evolution of the antibodies further, Wherry says. So a person will be better equipped to fight off whatever variant the virus puts out there next.

“Based on all these findings, it looks like the immune system is eventually going to have the edge over this virus,” says Bieniasz, of Rockefeller University. “And if we’re lucky, SARS-CoV-2 will eventually fall into that category of viruses that gives us only a mild cold.”

Source : NPR

Triage Protocols Made Public by Alberta Health Services

Jay Rosove wrote . . . . . . . . .

The term “triage” may be a scary one to hear, but Alberta’s health authorities are preparing its staff and the public for the possibility of that extreme measure.
When triage is declared health officials must decide which critically ill patients are eligible to receive care and which are not.

A 52-page document outlining how life and death decisions will be made if the province’s health-care system is overwhelmed past its breaking point has been posted publicly by Alberta Health Services.

The framework for the critical care triage protocol in Alberta describes the procedure that will be put into place when all available resources and mitigating steps for critical care have been exhausted.

“We’ve started the educational process,” AHS CEO Dr. Verna Yiu told reporters on Thursday.

According to the AHS triage framework, the decision to activate the protocol would be up to Dr. Yiu, “in consultation with the AHS Executive Leadership Team.”

“Basically this week was really sharing with our staff about what it is,” said Dr. Yiu, “and really setting up the infrastructure in place so that we – if we had to use it, again this would be an absolute, absolute last resort – that the staff are ready and trained and prepared.”

According to the AHS document, the critical care triage protocols are designed to “create an objective process to guide health-care professionals in making difficult determination of how to allocate resources to critically ill adult and pediatric patients when there are not enough critical care resources for everyone.”

WHEN TRIAGE MEASURES CAN BE TRIGGERED IN ALBERTA

The framework divides the province-wide triage measures into two possible phases, based on the severity of surging volumes of critical care patients.

When the usual number of critically ill patients is exceeded, and all available critical care surge beds is at 90 per cent or greater, the AHS triage guidelines state that should be considered a “Major Surge” and “Phase 1 Triage may be required.”

According to the AHS framework, Phase 1 triage would mean “eligibility assessment for entry into critical care are based on one year expected mortality of approximately greater than 80 per cent.”

In other words, the greater your likelihood of survival, the better chances you have of receiving care.

Phase 1 triage would not affect pediatric patients, however Phase 2 would.

The triage guidelines state that Phase 2 may be required in the event of a “Large Scale Surge.”

According to the framework, a large scale surge is when “critically ill patient demand exceeds available capacity and human resources,”

“All feasible strategies to maximize staffing resources, staffing functions, supplies and equipment and access to invasive mechanical ventilation will have been used prior to initiation of this triage phase,” the document reads. “Provincial occupancy of available critical care surge beds is 95 per cent or greater.”

In a Phase 2 triage scenario patients would receive eligibility assessments, and current critical care patients would receive a “discontinuation assessment.”

When the triage protocol is active, consent from patients or their families would not be required to withhold or withdraw care.

Vaccination status will not be a consideration on whether a patient is treated.

HOW CLOSE IS ALBERTA TO ACTIVATING TRIAGE?

Dr. Neeja Bakshi, a general internist with primary inpatient practice at Edmonton’s Royal Alexandra Hospital, told CTV News Edmonton on Friday she believes the province’s ICUs could “potentially” be overrun within the next 12 to 14 days.

“Whether or not that’s to be the time we have that means that’s going to be the time we have to enact the protocol is a bit of a moving target,” said Dr. Bakshi. “It depends on resources and how much we can try to do within the current system.”

“This is also why we are starting to educate the folks that might be involved in the triage protocols right now.”

As the fourth wave of COVID-19 surges across Alberta, the province has begun to implement extraordinary measures to make room for the daily average of 20 new patients being admitted into the province’s ICUs.

While Ontario has agreed to accept patients from Alberta, Dr. Yiu said on Thursday that AHS is also in conversation with other provinces about sending patients if needed as well.

‘We need to bend that curve’: Alberta could transfer ICU patients to Ontario as hospitalizations near 900
According to AHS, field hospitals in Edmonton and Calgary have also been prepared.

When asked about triage protocols and ICU care rationing, Dr. Yiu stopped short of making any predictions.

“From our perspective the numbers are changing daily and almost hourly… Things that were projected from last week already (are not) accurate this week,” she said. “It’s related to the fact that we are continuing to find additional capacity.

“But it comes at a cost. And that cost is that when we start reducing the procedures and postponing procedures. That’s how we’re finding a lot of the capacity.”

The AHS CEO stressed the importance of getting every eligible Albertan vaccinated in order to avoid extreme measures like triage.

“I just can’t say enough how important it is for Albertans to go out and get vaccinated,” she said.

On Friday, the province announced 80 per cent, or more than 3.1 million of eligible Albertans, have received at least one dose of a COVID-19 vaccine.

Alberta has 310 ICU beds including 137 surge beds, Dr. Yiu said. Eighty-six per cent of those beds are occupied – largely by COVID-19 patients.

Dr. Yiu said the province currently has over 600 ventilators and an additional 200 “less than optimal ventilators,” which “could be used.”

According to the province, there are 911 hospitalizations due to COVID-19 with 215 of those in ICUs, as of Friday.

Alberta has 19,201 active cases of COVID-19.

The province has seen 2,523 deaths related to COVID-19.

Source : CTV


Read more at Alberta Health Services

Critical Care Triage during Pandemic or Disaster – A Framework for Alberta . . . . .

Is a Combo COVID/Flu Shot on the Way?

Dennis Thompson wrote . . . . . . . . .

During the next few weeks or months, you might find yourself dropping by the doctor’s office or pharmacy to get your annual flu shot along with a dose of COVID vaccine.

Unfortunately, you’ll have to get two individual jabs. Though at least two drug companies are working on a combo flu/COVID booster, the single-dose shot won’t be ready for this flu season.

But rest assured that it’s perfectly safe to get your flu shot and COVID vaccination during the same visit, infectious disease doctors say.

Getting several vaccinations at once has been standard medical practice for decades now, and these combos have never caused any harm, said Dr. William Schaffner, medical director of the Bethesda, Md.-based National Foundation for Infectious Diseases.

“It certainly hasn’t inhibited the armed forces,” said Schaffner, a professor of infectious disease and preventive medicine at the Vanderbilt University School of Medicine in Nashville, Tenn. “When you’re a recruit, you get needled. You get a whole bunch of vaccines simultaneously.”

It doesn’t overwhelm your immune system, he said.

“And the CDC [U.S. Centers for Disease Control and Prevention] has said explicitly you can get your first, second or — if they’re recommended — booster COVID vaccines at the same time that you get your flu shot,” Schaffner added.

Anticipating that annual COVID boosters will be needed in the future, the pharmaceutical companies Moderna and Novavax both have announced that they are developing a combination flu/COVID vaccine.

Moderna told investors last week it hopes eventually to build an annual combo vaccine that protects against a variety of respiratory viruses, including influenza, COVID and respiratory syncytial virus (RSV).

Meanwhile, Novavax said it has initiated early-stage clinical trials to test a combined flu/COVID vaccine.

Don’t go looking for either combo shot this flu season, said Dr. Amesh Adalja, senior scholar with the Johns Hopkins Center for Health Security in Baltimore.

“I do not think that this is going to be something available in the short term, especially not for this flu season as flu vaccinations have already become available,” he said.

Schaffner agreed.

“They’re looking to the future,” Schaffner said of the drug companies. “They think COVID boosters will be necessary, and they’re even laying their bet this might be a good idea on an annual basis, because that would be the schedule in which you would need to get flu vaccine. They’re thinking about that pretty seriously and have invested a bunch of science in it.”

Adalja says the combo COVID/flu shot could be a smart idea, if it turns out we do need boosters against COVID.

“The more vaccines that can be packed into one shot the better, as it makes getting vaccinated and staying on schedule convenient,” he said. “Whether this is a vaccine everyone needs depends upon the data supporting the need for booster COVID vaccinations, which has not been fully presented.”

Lots of other combination vaccines are already on the market, like the tetanus/diphtheria/pertussis (Tdap) and the measles/mumps/rubella (MMR) shots, Adalja said.

Whether a COVID/flu combo would be safe and effective will depend on the immune reaction that’s produced by a single jab, Adalja said.

He noted that the MMR and varicella (chickenpox) vaccines are separated for the first dose, and then combined into a single MMRV shot for a person’s second dose.

That’s because when the combo MMRV is given as one shot for the first dose, it produces more adverse reactions than breaking it into two separate jabs, Adalja said.

Either way, infectious disease doctors like Schaffner and Adalja are bracing for a flu season that could be worse than last year. According to the CDC, flu cases were at an all-time low in 2020-2021 as pandemic protections such as masking and social distancing also served to keep influenza at bay.

“People are concerned because we’re doing exactly the opposite of what we did last year,” Schaffner said. “We’re going out instead of staying home. The kids are in school rather than learning virtually. So we anticipate there will be influenza this year. We can’t tell you how much, but we think there will be influenza, so we’re going to have to reintroduce everyone to this other respiratory virus which is also nasty — influenza.”

Schaffner is also worried that public health experts will be promoting flu shots “at a time of vaccine fatigue,” during which people might also be touting COVID booster shots among some groups.

But it’s still anyone’s guess what will happen this flu season, Adalja noted.

“It’s unclear whether influenza will be a major factor this season because there has not been much flu circulating even in the Southern Hemisphere, and there are some residual COVID-19 mitigation measures that people are taking,” Adalja said. “But influenza has a special status, and it is very important to be prepared for whatever the season may hold.”

Source: Health