With a sniff or a swallow, new vaccines aim to put the brakes on Covid-19 spread

 By Brenda Goodman, CNN

Updated 1426 GMT (2226 HKT) July 22, 2022

https://edition.cnn.com/2022/07/18/health/mucosal-immunity-covid-19/index.html?

(CNN)Injected vaccines against the coronavirus that causes Covid-19 have been hugely successful, saving nearly 20 million lives globally in their first year of use and slashing the pandemic's death toll by an estimated 63%, according to a recent study. Yet good as these shots are, they have not stopped the virus from spreading from person to person.

As the SARS-CoV-2 virus spreads, it changes. That's helped it get past our firewalls, the immunity created by vaccines or left behind after we recover from an infection. Which is why, well into the third year of the pandemic, we're in the midst of another wave of Covid-19 caused by the most immune-evasive variant yet, BA.5. And more variants are coming.

Even as vaccine manufacturers race to update the first-generation shots in the hopes of patching up our protection for the fall, other scientists are taking a different approach, making vaccines delivered via nasal sprays or tablets that would deploy more immune defenders to the body's front lines: the lining of the mouth, nose and throat.

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"The hope is to shore up the defenses right there in the nose so that the virus can't even replicate in the nose," said Dr. Ellen Foxman, an immunobiologist at the Yale School of Medicine. "And then someone who has a really effective mucosal vaccination can't even really support viral replication or make viruses that can infect other people.

"That would be like the holy grail," said Foxman, who helped plan the International Congress of Mucosal Immunology meeting this week in Seattle, which is sponsored by pharmaceutical companies Pfizer, Janssen and Merck.

If it works, there's hope that mucosal immunity could slow the development of new coronavirus variants and finally bring the Covid-19 pandemic under control.

There's a long way to go before that happens, however, and many scientists say the approach needs an injection of funding to accelerate the pace of development, much in the same way the billions of dollars doled out by Operation Warp Speed delivered the first generation of Covid-19 vaccines in record time.

An old approach meets new technology

The idea behind vaccinating the mucosa -- the lining of "the tube" (as mucosal immunologists refer to it) that runs from our nose and mouths to our lungs and guts -- isn't new. There are nine existing vaccines that work this way, including oral drops that protect against polio, cholera, salmonella and rotavirus, and a nasal spray, FluMist, that inoculates against the flu.

The quest for longer-lasting Covid-19 vaccines

Most are based on the oldest types of vaccine technologies, using killed or weakened versions of a virus or bacteria to teach the body how to recognize it and fight it off when a real infection gets underway.

Because of those actual pathogens, some people can't use these kind of vaccines. It's risky to expose certain groups -- including pregnant women and those with weakened immune systems -- to even weakened viruses.

None has achieved the goal of blocking the transmission of an infection, but that may be because they haven't gotten the same kind of investment as injectable vaccines, says Ed Lavelle, an immunologist at Trinity College in Dublin.

"What hasn't really happened with mucosal vaccines is kind of huge advances in technology that have happened with injectable vaccines, even before Covid," Lavelle said.

That may be about to change, however.

Can nasal spray vaccines put the brakes on new variants?

More than a dozen nasal spray vaccines against Covid-19 are being tested around the world. Many use new kinds of technologies, like delivering instructions for making the spike protein of the coronavirus through harmless Trojan horse viruses. Others aim to deploy the mRNA technology that was so successful in the injectable vaccines in the form of a nasal spray.

One company, Vaxart, has even made a tablet that delivers instructions for making parts of the new coronavirus to the gut, which then builds immunity in "the tube."

In animal tests, hamsters vaccinated in the nose or mouth have been less likely to spread a SARS-CoV-2 infection to uninfected animals that are in separate cages but share the same air.

"What we found is that if you did an oral immunization, you inhibited the ability for that breakthrough to infect other animals," said Sean Tucker, chief scientific officer for Vaxart.

The Vaxart tablet, which is about the size and shape of an aspirin, uses an adenovirus -- the same delivery system utilized by the Johnson & Johnson and AstraZeneca Covid vaccines -- to ferry instructions for making parts of the SARS-CoV-2 spike protein into cells in the gut, which stimulates the release of antibodies in the nose and mouth.

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In an early trial that included 35 participants, 46% had an increase of antibodies in their nose after taking the tablet vaccine. Those who did seemed to create a broad spectrum of immunity to a number of types of coronaviruses, and they appeared to hold on to that protection for about a year. That may be a bit longer than injectable vaccines, though more research is needed to confirm those results.

Tucker is presenting these early results Monday at the Seattle conference. He says they'll also be published as a preprint study in the coming days.

A phase 2 trial of a tablet with a slightly different formulation, involving almost 900 participants, is also underway, Tucker says. It is scheduled to be completed next summer.

Most of the mucosal vaccines under development are designed to be delivered as a squirt of liquid or mist up the nose, and many are intended to be used as boosters in people who've had a complete primary series of Covid-19 vaccines.

"I don't think of them as nasal vaccines. I think of them as nasal boosts," said Jennifer Gommerman, an immunologist at the University of Toronto who specializes in tissue-specific immunity.

That's important, Gommerman says, because nasal vaccines -- like FluMist -- haven't really worked all that well.

The next generation of inoculations will be something different, she says. They will build on the body-wide immunity that was created by shots; they'll just redeploy it to the nose and throat where it is needed most, she says.

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"But here, we're actually talking about something else, where we're talking about building on the systemic immunity that was induced by a vaccine to a three shots of mRNA and then training that systemic immunity to go to the upper respiratory tract by boosting through the nose," Gommerman says.

One such approach was recently tested by Akiko Iwasaki, an immunobiologist at Yale University. According to their preprint study, Iwasaki and her team inoculated mice with a low dose of Pfizer's Comirnaty mRNA vaccine and followed up two weeks later with a boost of mRNA vaccine delivered via a nasal spray. The low dose of the injected vaccine was meant to simulate waning immunity. Other groups of mice got only an injection or only a dose of vaccine in the nose.

Only the group that got the injection followed by the nasal spray developed robust immunity against the Covid-19 virus.

"That approach we have shown in the mouse model to be 100% protective against lethal dose of SARS-CoV-2 infection, and it dramatically reduces the viral load in the nose and in the lung," Iwasaki said.

Going for IgA antibodies

Mucosal vaccines also target a slightly different part of the immune system than shots.

Injections trigger the body to make antibodies against the virus that causes Covid-19. Most of these are Y-shaped proteins called IgG antibodies that are programmed to recognized and block specific parts of the SARS-CoV-2 virus along its spikes, the parts of the virus that latch onto and infect our cells.

A much smaller portion of these are IgA antibodies, and they look like two Ys joined together at their tails and turned sideways so it looks more like a dog bone, Gommerman says.

Like bouncers at a bar, IgA antibodies are the primary immune molecules on guard in the mucosa.

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These molecules are beefier than IgG antibodies. They have four arms instead of two, and they're special because they're less picky about what they grab onto than IgG antibodies.

"They might be a little more promiscuous in the way they recognize different variants. And that's obviously a plus," Gommerman said.

Shots increase IgA antibodies in the nose for a short time, but the hope is that mucosal vaccines will really ramp up the population of these sentries and help them stay active for longer.

"Whether they'll be able to confer complete sterilizing immunity, that's a very tall order," Gommerman said. "But we should be now working on ways to slow down person-to-person transmission, because this virus continues to mutate and then fools our immune system and gets past that mucosal layer.

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"This is now a very contagious virus," she said.

Iwasaki says she would love to move her vaccine out of animal studies and into clinical trials in people.

"We're still at the stage where we're kind of struggling to raise money, even make the vaccine for human use, because it takes millions of dollars, and we are not sitting on that kind of money for research lab," she said, "so not yet."

https://edition.cnn.com/2022/07/18/health/mucosal-immunity-covid-19/index.html?

Coronavirus can be contagious during a Paxlovid rebound, researchers warn, even if people don't have symptoms

 

By Brenda Goodman, CNN

Updated 2003 GMT (0403 HKT) July 30, 2022

This story originally published on May 31, 2022.https://edition.cnn.com/2022/07/30/health/paxlovid-rebound-contagious-study-wellness/index.html

(CNN)People who have a Covid-19 rebound after treatment with the antiviral drug Paxlovid can be contagious and may not know it because they might not have symptoms, researchers warn.

"People who experience rebound are at risk of transmitting to other people, even though they're outside what people accept as the usual window for being able to transmit," said Dr. Michael Charness of the Veterans Administration Medical Center in Boston.

Covid-19 cases that return after antiviral treatment puzzle doctors

Charness and his colleagues recently collaborated with a team of researchers at Columbia University to look into cases of Covid-19 that return after Paxlovid treatment. He said they've found at least two instances in which people have transmitted to others when their infection recurs.

In one case, a 67-year-old man infected a 6-month-old after a half-hour near the child.

The man was 12 days past his first positive Covid-19 test. He had taken a five-day course of Paxlovid and was feeling better. He didn't have any symptoms when he saw the baby, who was his grandson, but about eight hours later, he started to feel ill again.

The baby tested positive about three days later, as did both of his parents. Neither the baby nor its parents had any other close contacts before they got sick.

"It indicates that you can transmit during rebound even before you develop symptoms," Charness said. "And you know, we studied a small number of people. It's certainly conceivable that there are other people out there who don't have symptoms and still have a viral rebound."

In another instance, a 63-year-old man infected two family members during three days of relapse after Paxlovid.

Take precautions after Paxlovid

Based on this research, the US Centers for Disease Control and Prevention issued new guidance last week for people experiencing Covid-19 rebound after Paxlovid.

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The CDC said people who test positive again and whose symptoms come back after finishing their antiviral pills should restart their isolation period and isolate for five full days. The agency says people can end their isolation period after those five additional days as long as their fever has been gone for 24 hours without fever-reducing medication and they're feeling better. The agency also recommends that people wear a mask for 10 days after their symptoms come back.

The findings and guidance come as Paxlovid use has increased in the United States. According the White House, over the past two months, filled prescriptions for Paxlovid have climbed from about 27,000 a week to 182,000 a week.

The administration credits the increase to its test-to-treat program, which created one-stop hubs in grocery and drug stores where people could take a Covid-19 test and immediately receive and fill a prescription for antiviral medications. The antiviral drugs should be taken within the first few days of symptoms.

The drug works well. In clinical trials, Paxlovid reduced the odds that a person at risk of severe Covid-19 would need to be hospitalized by almost 90% compared with a placebo.

Opinion: Rebound after taking Paxlovid is the latest twist in the Covid-19 puzzle

For that reason, the CDC says, early treatment with this medication is still recommended.

As helpful as it is, though, researchers say people should be aware the drug may not completely extinguish the infection.

Charness and his co-authors have now collected at least 10 such cases of Covid-19 recurrence after Paxlovid. Half of them have come from just two families, leading the researchers to conclude that such cases are not all that rare.

The research is shared as a preprint. It has not been scrutinized by outside researchers or published in a medical journal.

Genetic testing suggests that when people get a second round of Covid-19 after Paxlovid, it's not because they've been infected by a different strain of the virus. There's also no sign that the virus has changed or mutated to develop some kind of resistance to the drug.

So far, rebound cases have been mild. There haven't been any reports of severe disease during a Covid-19 relapse. Because of this, the CDC says, there's no reason to think that more treatment is needed.

Cause still not known

Why this might be happening is still a mystery.

In his studies, Charness said, the researchers watched the amount of virus in a person's body -- called their viral load -- go down on Paxlovid treatment.

"People take Paxlovid, and what we know it does very well is, it blocks viral replication," he said. And so the levels of virus go down. But then in some people -- no one knows how many, because not enough people have been studied -- levels of the virus begin to climb again nine to 12 days after they first test positive, Charness said.

It's not entirely clear that that rebound is linked to Paxlovid. In studies of more than 2,200 Covid-19 patients, Pfizer, the company that makes the drug, said there were a few patients who had their Covid-19 come bouncing back after a negative test, but they were in the group that took Paxlovid as well as in those who got the placebo, suggesting that Covid just reappears in some people, even without treatment.

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Charness' team has done its own comparison study, however, and found something different. When researchers looked at 1,000 cases of Covid-19 diagnosed between December and March in players and support staff of the National Basketball Association who had not taken the drug, they didn't find any cases of Covid-19 returning. This study is still unpublished.

They say more research is needed to understand whether there could be any connection to the drug.

Charness said the fact that the infection can come back this way after treatment presents some questions. For one, would rebound be as common in people who started the drug later, maybe on day four or five after their first symptoms, after their immune systems have had longer to initially see the virus? Would a longer course of treatment -- maybe taking the drug for six or seven days, rather than five -- lower the risk that the virus would come back?

"No one knows," he said. "Somebody should be studying this."

https://edition.cnn.com/2022/07/30/health/paxlovid-rebound-contagious-study-wellness/index.html

Updated Covid-19 booster shots could be available in September

 By Naomi Thomas, CNN

Updated 1951 GMT (0351 HKT) July 29, 2022

https://edition.cnn.com/2022/07/29/health/updated-covid-boosters-fall/index.html

(CNN)Moderna and Pfizer booster shots updated to target Omicron coronavirus subvariants could be available in early fall, pending signoff by federal health agencies, the US Department of Health and Human Services said Friday.

The US Food and Drug Administration advised vaccine makers in June to update the boosters to add an Omicron BA.4/5 component and create a bivalent booster.

Why the Omicron offshoot BA.5 is a big deal

"Pfizer and Moderna have indicated that they anticipate the modified vaccines being available as early as September," an FDA spokesperson said.

HHS announced Friday an agreement to purchase 66 million doses of Moderna's bivalent booster shot for potential use in fall and winter. That's in addition to 105 million bivalent boosters the US government has purchased from Pfizer.

The FDA spokesperson said that agency "has been working closely with vaccine manufacturers over the past several months to ensure that modified COVID-19 vaccines are available this fall to meet evolving public health needs, following FDA's review for safety and effectiveness. The agency will work expeditiously to review submissions to make COVID-19 vaccines available."

Updated shots would need to be authorized by the FDA and recommended by the US Centers for Disease Control and Prevention. Pfizer and Moderna have not responded to requests for comment.

Currently, people 5 and older are eligible for a first booster shot, but only those 50 and older and some immunocompromised people are eligible for second boosters.

Should you get your booster now or wait until the fall? An expert weighs in

Adults 50 and older who have not received a second booster dose with current Covid-19 vaccines "should consider doing so now," the FDA spokesperson said. "You can still benefit from existing booster options and leave time to receive an updated booster in the fall."

At this time, the FDA is not considering authorizing a second booster for otherwise healthy adults under 50 with the original formulation of the Covid-19 vaccines.

"Once boosters containing a BA.4/5 component become available, individuals may consider getting one following an appropriate interval following their prior dose," the spokesperson said.

In late June, vaccine makers said boosters updated to target Omicron showed a stronger immune response than the current vaccines.

Combined, the US government's agreements with Moderna and Pfizer would make about 171 million bivalent vaccine booster doses available for the fall and winter, should they be authorized and recommended.

But the Biden administration added in its announcement Friday that that would not be enough for every US resident. Although both agreements include options to purchase a total of 600 million doses -- 300 million from each company -- those options "can only be exercised with additional funding from Congress," the announcement said.

"We look forward to receiving these new variant-specific vaccines and working with state and local healthcare partners to make the vaccines available for free in communities around the country this fall," said HHS Assistant Secretary Dawn O'Connell, who leads the Administration for Strategic Preparedness and Response, in the HHS news release.

CNN's Jacqueline Howard, Katherine Dillinger and Jamie Gumbrecht contributed to this report.

https://edition.cnn.com/2022/07/29/health/updated-covid-boosters-fall/index.html

Should you get your booster now or wait until the fall? An expert weighs in

 By Deblina Chakraborty, CNN

Updated 0944 GMT (1744 HKT) July 21, 2022

https://edition.cnn.com/2022/07/21/health/omicron-booster-vaccine-coronavirus-wellness/index.html

(CNN)Covid-19 cases are increasing across the United States once again, driven by the most contagious strain of the coronavirus yet, BA.5. Federal health officials are urging Americans to stay up to date on their vaccines by getting additional boosters if they are due for them, but many people are confused.

Who is eligible for boosters now? Will all adults be able to get a second booster soon? If new boosters are being developed for the fall, should people wait until then or get boosted now? How long should people wait for their booster after having contracted Covid-19? And what about kids — should they get boosters now or wait until school starts?

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To help us navigate these questions, I spoke with CNN Medical Analyst Dr. Leana Wen, an emergency physician and professor of health policy and management at the George Washington University Milken Institute School of Public Health. She is also author of "Lifelines: A Doctor's Journey in the Fight for Public Health."

CNN: Can you start by reminding us who is eligible for booster doses at this time?

Dr. Leana Wen: The latest guidelines from the US Centers for Disease Control and Prevention are as follows: If you are 50 and above, you are eligible for two booster doses of the mRNA vaccine (Pfizer/BioNTech or Moderna). The first booster dose is given at least five months after your primary vaccination (which is either two doses of the mRNA vaccine or one dose of Johnson & Johnson vaccine). The second booster dose is given at least four months after your first.

If you are between 5 and 49, you are eligible for your first booster dose, if it's been at least five months since your primary series. Children younger than 5 just started receiving their initial vaccinations and therefore are not eligible for additional boosters yet.

There are a couple of exceptions. The first is if you are moderately or severely immunocompromised. Those individuals are generally able to get a third booster dose, with an interval between booster doses that's slightly condensed compared with the intervals for people who aren't immunocompromised. Another exception is for those who received an initial Johnson & Johnson one-dose vaccine, then subsequently got another J&J vaccine as their first booster. Those people, no matter their age, are able to get a second booster of an mRNA vaccine if it has been four months since their second J&J shot.

CNN: Will adults who are under 50 be able to get their second booster anytime soon?

Wen: Federal health officials are discussing expanding the eligibility of second boosters. My best guess is that in the next month or so, they will make at least a permissive recommendation, meaning that those who want to get another booster should be able to receive one.

The decision about who should get a booster and how often is not straightforward. At the end of the day, there is a fundamental disagreement among scientists and public health experts on the purpose of the Covid-19 vaccinations. Some believe that the goal of these vaccines is to prevent severe illness, and as long as the vaccines continue to protect against hospitalization and death, additional boosters aren't needed. Others point to vaccines also being able to reduce symptomatic illness. That effect is not as long-lasting as the protection against severe illness, so those who hold this second point of view would advocate for more frequent boosters. The answer isn't straightforward.

CNN: Are there certain people you'd say really need to get boosted now, if they haven't already?

Wen: Here's how I think about the three groups for whom boosters are more urgent if they have not received them.

A nurse preps a syringe at a pop-up Covid-19 vaccination site at the Albanian Islamic Cultural Center, April 8, 2021, in the New York borough of Staten Island.

We know that age is a major risk factor for severe illness, and also that the protection against severe illness wanes in older individuals. People 60 and older, and who are 50 and older with chronic medical conditions, should really receive the two boosters that they are eligible for.

Those who are immunocompromised and are eligible for more boosters should get them, since they, too, are among those who are most vulnerable to severe outcomes from Covid-19.

Beyond that, all adults should receive their first booster. We know that the first booster really increases protection, including against severe disease. If you are 18 and older and have not yet had any vaccines beyond your primary vaccination, you should get your booster now.

CNN: What about children? Should they also get their boosters if they're eligible?

Wen: The data for boosting kids is much less compelling than for adults. The CDC does recommend boosters for children 5 and older, and I think a lot of parents and caregivers will want to follow that guidance. But the urgency is not the same as it would be for adults, especially older adults, who have not yet been vaccinated.

CNN: Let's talk about timing. Some people are worried that if they get vaccinated now, they won't be able to get the Omicron-specific vaccines that may be coming out in the fall. Should that be a reason to wait?

Wen: For most people, I don't think this is a reason to wait. Here's why.

First, federal health officials have said that getting vaccinated now won't preclude you from getting an updated vaccine in the fall. It's worth stating here that it's not certain that these updated vaccines will become available. The one likely to become authorized is the "bivalent" vaccine, meaning that it will be a combination of the original vaccine and an Omicron subvariant vaccine.

Second, there is a lot of virus surging around now. Getting boosted now will protect you now, and if you need an additional level of protection in the fall and winter, you could get another dose then.

There's one crucial step to your Covid self-test you may be missing, experts say

Third, it's not entirely clear that the updated vaccine is going to be better than the vaccines available. The updated vaccine is intended to target the Omicron subvariants, which would be great if the vaccines were currently available, since those are the dominant variants in circulation. However, if they are going to be given in the fall, there is no guarantee that the Omicron subvariants are still going to be the main strains at that point. Of course, we hope that the updated boosters will be more effective than what we have now, but we don't know that's going to be the case — which is even more reason not to wait until then.

CNN: I've heard some people say, I'll wait to get a booster until right before a big trip. Does that make sense?

Wen: I can understand why some people might go with this approach. The booster does enhance protection against infection for a short time period after it's given, probably with maximal effect from about 10 days to three months. Someone who just got boosted could still contract Covid-19, but chances would be lower than if they got the booster, say, six months before.

Of course, there are other ways to reduce your risk of contracting Covid-19, too. If you are very concerned about getting the coronavirus, you should also wear a high-quality N95 or equivalent mask in indoor spaces and avoid crowded settings.

CNN: If someone has just recovered from Covid-19, how long should they wait before their booster?

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Wen: They are able to receive a booster as soon as they are 10 days past when they first started having symptoms and no longer have a fever, though I'd recommend that they wait a bit longer. That's because recent infection conveys good protection for a short period of time and reinfection within a three-month window is rare. To get the longest protection out of your next shot, you could wait three months after your infection to get the additional booster.

https://edition.cnn.com/2022/07/21/health/omicron-booster-vaccine-coronavirus-wellness/index.html