AstraZeneca’s COVID vaccine (pictured) is one of the first to receive authorization in the U.K. A number of exciting vaccines are still in the pipeline. Credit: Russell Cheyne Getty Images

Six months ago, as the northern hemisphere was still battling the coronavirus pandemic’s first wave, all eyes turned to the COVID-19 vaccines in late-stage clinical trials. Now, a year after the pandemic first erupted, three COVID vaccines have been given emergency authorization by either the U.S. or U.K., as well as other countries. Two of the vaccines, developed by Pfizer and BioNTech and Moderna, respectively, both employ a novel genetic technology known as mRNA. And the third is a more conventional vaccine developed by the University of Oxford and AstraZeneca that uses a chimpanzee virus to deliver DNA for a component of SARS-CoV-2, the virus that causes COVID. (Russia, China, and India have rolled out their own vaccines, but with the exception of a few countries, they have not been widely authorized elsewhere.)

But impressive as they are, these vaccines alone will likely not be sufficient to end the pandemic, experts say. Luckily, there are hundreds of other COVID vaccines under development—including many with new mechanisms of action—that could prove to be effective and cheaper, and easier to distribute.

“I believe that this virus is going to change and that the vaccines we have approved right now are just not going to be as effective as we think they are,” says Danny Altmann, an immunologist at Imperial College London. SARS-CoV-2 has already evolved several new variants—including the ones first identified in the U.K. and South Africa, which are more transmissible (though not—for now, at least—more deadly).

Gregory Poland, a vaccinologist at the Mayo Clinic, agrees it is far too early to think we have this virus beat. He points out that no vaccine for a coronavirus has ever been deployed in a public vaccination program. And mRNA vaccines such as Pfizer’s and Moderna’s—touted by many as the future of vaccinology—have never previously been brought to market. “We don’t know what we don’t know. We have no idea what surprises we might find in a virus that we’ve only been aware of for a year,” says Poland, who co-authored an extensive review of COVID-19 vaccine candidates in the Lancet last October. “And the history of vaccinology—in which I’ve been involved for four decades—is amply littered with things we thought we knew.”

What happens if somebody is vaccinated but contracts COVID anyway? Would they suffer an even worse case of illness, a phenomenon known as antibody-dependent enhancement? Or in a less dramatic scenario, what if the vaccines prevent immunized individuals from falling ill but do not prevent them from infecting others? The latter could actually worsen the pandemic if vaccinated individuals think they are safe and become asymptomatic carriers. Moreover, people worldwide display a wide range of natural immunity to the virus, so there may be a similar diversity in vaccine responses. “There are lots of booby traps that could lie in wait,” Poland says.

Furthermore, the vaccines from Moderna and Pfizer have logistical issues that prevent them from being easily deployed globally. Pfizer’s vaccine needs to be stored at –70 degrees Celsius—colder than Antarctica’s average temperatures—in freezers that cost many thousands of dollars. Moderna’s can be stored at –15 degrees C, but because of freezer requirements, it still has little chance of reaching rural corners of India or Africa or poor, densely packed neighborhoods in South America. As long as vaccines are fragile, expensive and difficult to distribute, the pandemic will continue.

But by far the most important issue, Altmann says, is “durability”: how long people remain immune after vaccination. If a vaccine confers immunity for only a few months rather than many years, little progress will have been made in six months. By then we could be faced with more virulent forms of the disease swirling around the globe.

The good news, however, is that “second generation” vaccines are being developed by researchers, many of whom are working with novel techniques. “We have an embarrassment of riches,” Altmann says. “One thing that certainly hasn’t been appreciated by most people is that, on the back burner, the field of vaccinology has been steaming ahead over the past 15 years, developing a range of incredibly snazzy strategies.”

There are nearly 240 novel vaccine candidates in development, waiting in the wings for their moment. Here are a few that show the most potential.

SELF-AMPLIFYING RNA (IMPERIAL COLLEGE LONDON)

Similar to the approved mRNA vaccines, this one inserts genetic material from the virus directly into human cells, spurring the body to manufacture the famed “spike” protein that covers the surface of SARS-CoV-2. And like mRNA vaccines, Imperial College London’s design only delivers the genetic material, not the actual virus, so it is unlikely to exacerbate illness if people are infected following vaccination. The twist with this vaccine is that it has been modified to turn the body’s own cells into factories that continually churn out spike proteins on their own—meaning a booster shot will not be necessary. Moreover, such “self-amplifying” RNA can reportedly be made in huge volumes for little cost. “I feel very excited about the way [this approach] may turn out to be like Pfizer’s and Moderna’s vaccines but even better,” says Altmann, who was not directly involved in developing this vaccine.

PROTEIN SUBUNIT (NOVAVAX)

Researchers at the Maryland-based start-up Novavax have focused on delivering the actual spike protein itself (rather than a whole virus or genetic material). They created the vaccine by engineering moth cells to churn out spike proteins in bioreactors at low cost. Furthermore, this vaccine can be kept at two to eight degrees C—normal refrigeration temperature—making it far more practical to distribute. The trick with this approach is the addition of an “adjuvant”—an additive that “soups up” the immune system’s response—made from saponin, a compound derived from the bark of the Chilean soapbark tree. “Engineered protein technology has been tested and proved in the past—it just takes a little more time to produce than RNA,” explains Gregory Glenn, president of research and development at Novavax.

DESIGNED PROTEIN NANOPARTICLE (INSTITUTE FOR PROTEIN DESIGN, UNIVERSITY OF WASHINGTON)

Like Novavax, University of Washington researchers have chosen to deliver proteins from SARS-CoV-2 as their weapon of choice. But instead of injecting the entire spike protein, they have homed in on the virus’s “Achilles’ heel”: the receptor binding domain (RBD), the portion of the spike protein that directly fuses with human cells. Neil King, a biochemist at the university’s Institute for Protein Design, has created a vaccine delivered by spherical “nanoparticles” shaped like soccer balls. Synthetically manufactured RBD proteins are affixed to the nanoparticles in regular arrays. This design makes the vaccine capable of eliciting antibody responses at least 10 times higher than those that use the whole, natural spike protein, King says. “We aren’t just taking existing proteins and tweaking them a little bit—we are making completely new ones to do exactly what we want,” he notes. The vaccine is currently being tested in early-stage, or phase I, trials with human volunteers. If successful, it could reach the public later this year.

OTHER VACCINES IN THE PIPELINE

These are just a few of the vaccine candidates in development. Others that could help slow the pandemic, including the vaccine developed by Sinovac Biotech in China, utilize more conventional designs, such as an inactivated virus (a technique used to help conquer polio and still used in many influenza vaccines). It remains to be seen how well all of these approaches may work. But with so many efforts underway, there is good reason to hope that the end of this pandemic nightmare is in sight.

And when it does end, scientists will have many tools ready-made for when the next pandemic hits.

Read more about the coronavirus outbreak from Scientific American here. And read coverage from our international network of magazines here.

Source: https://www.scientificamerican.com/article/the-second-generation-covid-vaccines-are-coming/

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Hand, foot, and mouth disease if a viral infection common in young children, and is more known for shutting down preschools and daycares.  However, all that has changed as the infection is now rampant on college campuses.

Health officials are saying that the unusual outbreaks striking those older are marked by a particularly nasty set of symptoms that include the usual blisters in the mouth and on the hands and feet, but also on the genitals. According to NBC News, health officials in several states are testing samples to determine which virus is responsible for these outbreaks. Several different viruses, including coxsackieviruses and enteroviruses such as EV-A71, can cause the symptoms of hand, foot and mouth disease.

“I have never seen this before,” said Dr. Roanna Kessler, medical director of the wellness center at Johns Hopkins University’s Homewood campus, which has been hit hard by the outbreak. So far, 129 students at the North Baltimore campus have been diagnosed with the illness. “In previous years we have usually seen it in only a handful of people.”

So far this year, Johns Hopkins, Princeton, Dartmouth, West Virginia University, Lehigh University, Wesleyan University in Connecticut and Mars Hill University in North Carolina have all reported outbreaks. Florida State University battled an outbreak in 2016.

And health officials don’t know why so many older teens and young adults are being affected, Kessler said. “We are wondering if it is a strain that people were not exposed to when they were younger,” she said. Medical journals have carried reports of a mutated strain of coxsackievirus A6 causing severe outbreaks in Asia and Europe.

NBC News did mention that college campuses — where students share bathrooms, desks, equipment and where they frequently share food and drink, embrace and kiss — are perfect grounds for spreading infectious diseases of all kinds.

According to the Mayo Clinic, hand, foot, and mouth disease is a mild, contagious viral infection common in young children. It is normally characterized by sores in the mouth and a rash on the hands and feet. Hand-foot-and-mouth disease is most commonly caused by a coxsackievirus. There’s no specific treatment for the infection, however, frequent hand-washing and avoiding close contact with people who are infected with hand-foot-and-mouth disease may help reduce your child’s or your risk of infection.

Source: https://www.thescoopradioshow.com/viral-outbreak-college-campuses-plagued-by-hand-foot-and-mouth-disease/

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But what officials with the CDC don’t know about acute flaccid myelitis, a polio-like illness that can cause paralysis, is nearly everything else.

What causes it is not clear. Why it affects some people and not others is unknown. Why it seems to spike every 2 years remains a mystery. How to treat it, too, has the CDC stumped. The agency has confirmed 62 cases in 22 states this year and are investigating another 65 reports of similar illnesses. But the who, what, where, and why of the disease are largely still unknown.

“The reason why we don’t know about AFM — and I am frustrated that despite all of our efforts, we haven’t been able to identify the cause of this mystery illness — we continue to investigate to better understand the clinical picture of AFM cases, risk factors, and possible causes of the increase in cases,” Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases, told reporters at a news conference this week.

“We know this can be frightening for parents,” Messonnier said. “I know many parents want to know what the signs and symptoms are that they should be looking for in their child.”

Parents, she said, should seek medical care immediately if a child suddenly has weakness or loss of muscle tone in the arms and legs.

The good news is that the disease is very rare. Only one in 1 million people are thought to get it. However, while some children do fully recover, research shows that AFM’s effects often linger. In a study published last yeary, children showed persistent weakness in the areas affected by AFM. New, yet to be published research suggests as many as 50% of children with AFM will require surgery to restore function. But, because outbreaks of AFM are a relatively new phenomenon and the number of children affected so far has been small, researchers have limited data from which to draw firm conclusions.

“We work with what we have,” says Priya Duggal, PhD, director of the genetic epidemiology program at the Johns Hopkins Bloomberg School of Public Health in Baltimore. “The depth of information that we have is helpful even if we do not have breadth of cases.”

Because the disease is more likely to strike children, and because of the mysteries of it and because of the dramatic health effects, it gets more attention than it might otherwise.

Despite the current alarm, the disease is not unheard of.

“In 2014, the first patient I saw was a baby, who had a sudden onset of weakness in one leg,” recalls Marc Patterson, MD. “The leg was flaccid and did not recover.”

Since then, Patterson, chairman of the division of Child and Adolescent Neurology at the Mayo Clinic in Rochester, MN, has seen several children diagnosed with what’s come to be called acute flaccid myelitis, or AFM, a very rare disease that causes nerve-damaging inflammation in the gray matter of the spinal cord.

AFM can lead to weakness or paralysis in the arms and legs. Cranial nerves also can be affected, which can make your face weak, eyelids droop, or make it hard to swallow. In the most severe cases, AFM can cause trouble breathing and may require ventilator support.

“This disorder presents just like paralytic polio used to present back in the 1940s,” says Patterson, who’s also a Mayo Clinic professor of neurology, pediatrics, and medical genetics. “This is another form of polio, and I think that people have not used the term because of the tremendous emotional significance.”

This year, the third outbreak of AFM is still underway. Such outbreaks have arrived every 2 years since 2014, and the CDC’s current tally includes nearly 400 confirmed cases over the past 4 years. The federal health agency acknowledges that gathering data about AFM is a relatively new process, and that may make it difficult to interpret and compare what they’ve learned from each outbreak.

The number of cases likely will rise as health agencies investigate and confirm potential cases, a process that can take lots of time.

“The CDC is very careful in taking time to identify cases, and there may be a jump in the number as cases go through the verification process,” says Kevin Messacar, MD, a pediatrician at Children’s Hospital Colorado who specializes in infectious diseases. As an assistant professor at the University of Colorado School of Medicine, he has seen 12 children with AFM since spring.

“Our situation here in Colorado is unique because our outbreak has been ongoing since March, while it has started elsewhere in the summer months,” says Messacar.

The disorder itself is not new, says Patterson, as similar but isolated cases have been reported over the years. “But I think it was the fact that it was a cluster that first drew attention to this in 2014.”

Viruses a Possible Trigger
Many AFM cases have been linked to enteroviruses. Such viruses are not uncommon. In fact, the CDC estimates they cause as many as 15 million infections each year and tens of thousands of hospitalizations. But most infections cause only mild symptoms, such as gastrointestinal upsets, cold-like discomfort, and fever. Sometimes, they cause no symptoms at all. But some experts suspect that the viruses somehow trigger AFM in a very small number of people, most of them children.

Children are quite vulnerable to viruses, says Messacar, because they do not have fully developed immune systems. So their bodies can’t combat infection as successfully as adults. But AFM can strike adults whose immune systems don’t work well, such as those being treated for cancer.

The symptoms of AFM arrive suddenly, usually within a week of being ill with a virus. An arm or a leg, for example, becomes weak or can’t be moved at all. In study findings presented at scientific meetings this year though not yet published, about 70% of kids with AFM have more than one affected limb.

To diagnose AFM, doctors will use magnetic resonance imaging (MRI) of the patient’s spinal cord for signs of inflammation. They may also perform a spinal tap to allow them to examine the spinal fluid for signs of the illness.

In addition to making a positive diagnosis of AFM, doctors also aim to find its cause.

“If we’re lucky, we can identify a virus,” says Patterson, “but there are many cases where you can’t positively identify a specific virus or other cause.”

Currently, no drug treatment exists to counter AFM’s attack on the nervous system. And, says Roberta L. DeBiasi, MD, a single drug may not be enough.

“It’s important to keep in mind that not all AFM is linked to … enteroviruses,” says DeBiasi, who heads the Division of Infectious Diseases at Children’s National Health System in Washington, D.C. “So, even if one specific treatment works for some patients, it may not necessarily represent a potential treatment for all AFM.”

Muscle Therapy a Key Treatment
aims to strengthen the muscles around the areas affected by the disease.

“If a child has weakness in a limb,” says Patterson, “one of the most important things we can do is get one of our occupational or physical therapy colleagues involved as soon as the child is well enough to participate.”

That kind of therapy requires a lot of hard work.

“At centers experienced in working with children affected by AFM, treatment often means weeks or months of intensive therapy done on a daily basis,” says Messacar.

And even that may not be adequate, he continues: “The vast majority of cases are left with residual weakness and in some cases complete paralysis of the affected areas.”

For those children, surgery may be needed to help them regain their abilities. Los Angeles-based surgeon Mitchel Seruya, MD, has performed a complex procedure called a nerve transfer on 15 children with AFM. His patients come from all over the country: Wisconsin, New Mexico, Texas, Minnesota, and elsewhere.

During the procedure, the surgeon reroutes a nerve from elsewhere in the body to take over the work of the nerve affected by AFM. For example, if AFM has caused weakness in a child’s shoulder and elbow but not in the hand or forearm, Seruya, an assistant professor of clinical surgery, can work with the healthy nearby nerves.

“If I want the elbow to move, I am going to steal a wrist flexor, meaning I’m going steal something that makes your wrist bend and divert it to your elbow,” says Seruya, who’s also director of the Brachial Plexus and Peripheral Nerve Center at Children’s Hospital Los Angeles.

The repairs get much more complicated if the whole arm has been paralyzed. In such cases, the nerves most often used are those involved in breathing, located near the sternum.

“That nerve has to span the chest and reach underneath the armpit to connect it to the arm itself,” Seruya says.

Researchers Look at Role of Genes
One of the key questions that needs to be answered is why some children — keep in mind, it’s a very small number — get AFM and most others don’t. For example, if an entire family or, say, a classroom gets exposed to an enterovirus, why doesn’t everyone get AFM? Researchers at Johns Hopkins University in Baltimore suspect that genetics may play a role. They are comparing the genetic makeup of children with AFM to see what they might have in common. And in families, they are also looking for genetic differences between family members who remained healthy and the child diagnosed with AFM.

“We hope this helps us to understand susceptibility to AFM,” says Priya Duggal, PhD, director of the genetic epidemiology program at the Johns Hopkins Bloomberg School of Public Health. “No doubt that this is not going away — we keep seeing it — and we need to better understand how to diagnose AFM, how to treat it, and what factors are causing it … or we will watch more kids become paralyzed.”

Since there’s no vaccine or drug treatment, the CDC’s prevention guidelines follow standard but effective advice for cutting the chances of getting or spreading a virus: Wash your hands often. Getting vaccinated for poliovirus may also offer protection. Finally, use mosquito repellent and other means of preventing mosquito bites, which can spread West Nile virus, another virus associated with AFM.

DeBiasi of Children’s in Washington wants parents to be vigilant but also to keep in mind that AFM is quite rare. It occurs in about one in 1 million children.

“If your child presents with weakness in one or more limbs, drooping facial features, like eyelids, seek care immediately,” she stresses, “particularly if your child has just had an upper respiratory infection or fever.”

Source: https://www.webmd.com/children/news/20181019/polio-like-virus-infects-kids-frustrates-doctors

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